Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)
Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02833350
Collaborator
(none)
578
150
7
21.7
3.9
0.2
Study Details
Study Description
Brief Summary
This is a multicenter, Phase II, randomized, double-blind, placebo-controlled, active comparator (Cohort 1 only), parallel-group, dose-ranging study to evaluate the efficacy and safety of GDC-0853 in participants with moderate to severe active RA and an inadequate response to previous methotrexate (MTX) therapy (Cohort 1) or MTX and tumor necrosis factor (TNF) therapy who may have also had exposure to no more than one non-TNF inhibitor biologic (Cohort 2).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
578 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Two-Cohort Randomized Phase II, Double-Blind, Parallel Group Study in Patients With Active Rheumatoid Arthritis Evaluating the Efficacy and Safety of GDC-0853 Compared With Placebo and Adalimumab in Patients With an Inadequate Response to Previous Methotrexate Therapy (Cohort 1) and Compared With Placebo in Patients With an Inadequate Response or Intolerance to Previous TNF Therapy (Cohort 2)
Actual Study Start Date
:
Sep 9, 2016
Actual Primary Completion Date
:
Jul 2, 2018
Actual Study Completion Date
:
Jul 2, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
Drug: GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Other Names:
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).
Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.
|
| Experimental: Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
Drug: GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Other Names:
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).
Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.
|
| Experimental: Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
Drug: GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Other Names:
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).
Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.
|
| Active Comparator: Cohort 1: GDC-0853 Placebo + Adalimumab Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
Drug: Adalimumab
Participants will receive adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks.
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).
Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.
|
| Placebo Comparator: Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).
Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.
|
| Experimental: Cohort 2: GDC-0853 High Dose Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
Drug: GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Other Names:
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).
|
| Placebo Comparator: Cohort 2: GDC-0853 Placebo Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion. |
Drug: Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
Drug: MTX
Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).
Drug: Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1) [Day 84]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
- Percentage of Participants With Adverse Events [Day 1 up to 8 weeks after last dose (up to Week 20)]
An Adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE was any experience that suggested a significant hazard, contraindication, side effect or precaution that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant.
Secondary Outcome Measures
- Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1) [Day 84]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
- Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2) [Day 84]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [Days 7, 14, 28, 56, and 84]
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response [Days 7, 14, 28, 56, and 84]
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response [Days 7, 14, 28, 56, and 84]
ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
- Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [Days 7, 14, 28, 56, and 84]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
- Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) [Days 7, 14, 28, 56, and 84]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
- Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR]) [Days 7, 14, 28, 56, and 84]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
- Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) [Days 7, 14, 28, 56, and 84]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
- Percentage of Participants With DAS Low Disease Activity [Days 7, 14, 28, 56, and 84]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2
- Percentage of Participants With DAS Remission [Days 7, 14, 28, 56, and 84]
The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6
- Percentage of Participants Meeting the Boolean-based Remission Criteria [Days 7, 14, 28, 56, and 84]
Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale).
- Change From Baseline in Clinical Disease Activity Index (CDAI) [Baseline, Days 7, 14, 28, 56 and 84]
CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest. Negative values indicate improvement/reduction in RA disease activity.
- Percentage of Participants Meeting the CDAI-based Remission Criteria [Days 7, 14, 28, 56, and 84]
Clinical Disease Activity Index is defined as CDAI= : SJC(28) + TJC(28) + PGA + MDG where TJC and SJC are the tender and swollen joint counts from 28 joints, PGA is the patient's global assessment of disease activity (on a 0-10 scale) and MDG is physician global assessment of disease activity (on a 0-10 scale). The cutoff value for CDAI remission is <=2.8.
- Change From Baseline in Simplified Disease Activity Index (SDAI) [Baseline, Days 7, 14, 28, 56 and 84]
Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity
- Percentage of Participants Meeting the SDAI-based Remission Criteria [Days 7, 14, 28, 56, and 84]
The SDAI was the numerical sum of five outcome parameter: SJC and TJC (based on a 28-joint assessment), PGA and MDG (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. The SDAI =< 3.3 indicates disease remission
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components [Day 84]
The 36-Item Short Form Health Survey (SF-36v2) is a questionnaire used to assess functional health and well-being and consists of eight domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The SF-36v2 is summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. The PCS and MCS scores range from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score [Day 84]
The FACIT-Fatigue Scale consists of 13 items designed to measure the degree of fatigue experienced by the patient in the previous 7 days. For each question, there are five possible responses: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), 4 (very much). A total fatigue score is calculated by summing all items, and possible total scores range from 0 (maximum fatigue) to 52 (no fatigue). A positive change from baseline indicates an improvement in the patient's fatigue (less fatigue).
- Change From Baseline in Tender/Painful Joint Count (68 Joint Count) [Days 7, 14, 28, 56, and 84]
Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness. 68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.
- Change From Baseline in Swollen Joint Count (66 Joint Count) [Days 7, 14, 28, 56, and 84]
Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling. 66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.
- Change From Baseline in Patient Assessment Score of Arthritis Pain [Days 7, 14, 28, 56, and 84]
Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain
- Change From Baseline in Patient Global Assessment Score of Arthritis Pain [Days 7, 14, 28, 56, and 84]
Participant-assessed arthritis pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of arthritis pain (0 mm=none; 100 mm=very severe). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change indicated a decrease in participant-assessed arthritis pain.
- Change From Baseline in Physician's Global Assessment Score of Arthritis [Days 7, 14, 28, 56, and 84]
Physician's assessment of participant's disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's assessment of the participant's disease activity (0 mm=very good; 100 mm=very poor). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change from baseline indicated an improvement in physician-assessed disease activity.
- Change From Baseline in C-Reactive Protein (CRP) Levels [Days 7, 14, 28, 56, and 84]
C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [Days 7, 14, 28, 56, and 84]
The Stanford Health Assessment Questionnaire disability index is a patient-reported outcome used to assess difficulty in performing activities of daily living. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. To respond to each question, a four-level response with higher scores showing larger functional limitations, was chosen. Scoring is as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. The composite HAQ-DI score is the mean of the eight domain scores and the score ranges from 0 (no functional impairment) to 3 (maximum functional impairment). A negative change from baseline indicates improvement.
- Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss) [Pre-dose (0 hours) up to 10 hours post-dose on Day 28]
The Pharmacokinetics (PK) evaluation may include, but will not be limited to, plasma GDC-0853 concentrations and population PK model estimated PK exposures (area under the plasma concentration-time curve [AUC]. AUC was measured in Nanograms(ng) per millilitre(mL)*hour (hr)
- Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss) [Pre-dose (0 hours) up to 10 hours post-dose on Day 28]
Cmax is the maximum (peak) plasma concentration over the dosing interval at steady state (ss)
- Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss) [Pre-dose (0 hours) up to 10 hours post-dose on Day 28]
Cmin is the minimum concentration over the dosing interval at steady state (ss)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have a diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA
-
RA disease activity by joint counts and laboratory markers of inflammation: greater than or equal to (>=) 6 tender/painful joints on motion (68 joint count) and >= 6 swollen joints (66 joint count) at both screening and Day 1 (randomization)
-
For MTX-inadequate response (IR) participants: must have had an inadequate response to MTX
-
For TNF-IR participants: must have had an inadequate response or intolerance to previous treatment with at least 1 and no more than 2 biologic TNF-alpha inhibitors and may have also been exposed to no more than one biologic non-TNF-alpha inhibitor
-
High sensitivity C-reactive protein of >= 0.400 milligrams per deciliter (mg/dL) for Cohort 1 and >= 0.650 mg/dL for Cohort 2 at screening
Exclusion Criteria:
-
History of or current inflammatory joint disease other than RA or other systemic autoimmune disorder
-
For MTX-IR participants: History of treatment with any TNF inhibitor, including biosimilar equivalents and history of treatment with biologic non-TNF-alpha inhibitor for RA
-
For all participants: Previous treatment with cell-depleting therapy including B cell-depleting therapy (e.g., anti-cluster of differentiation 20-directed therapy such as rituximab), tofacitinib, or other Janus kinase inhibitor(s), or alkylating agents
-
Current treatment with medications that are well known to prolong the QT interval at doses that have a clinically meaningful effect on QT
-
History of non-gallstone-related pancreatitis or chronic pancreatitis
-
Evidence of serious uncontrolled concomitant cardiac, neurologic, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal disease
-
Evidence of chronic and/or active hepatitis B or C
-
Women who are pregnant, nursing (breast feeding), or intending to become pregnant during the study or within 60 days after completion of the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pinnacle Research Group; Llc, Central | Anniston | Alabama | United States | 36207 |
| 2 | Arizona Arthritis & Rheumatology Associates, P.C. | Glendale | Arizona | United States | 85306 |
| 3 | Medvin Clinical Research | Covina | California | United States | 91723 |
| 4 | TriWest Research Associates, LLC | El Cajon | California | United States | 92020 |
| 5 | Saint Jude Heritage Medical Grp | Fullerton | California | United States | 92835 |
| 6 | Stanford University School of Medicine | Stanford | California | United States | 94305-5151 |
| 7 | RASF-Clinical Research Center | Boca Raton | Florida | United States | 33486 |
| 8 | ZASA Clinical Research | Boynton Beach | Florida | United States | 33472 |
| 9 | Clinical Research of West Florida | Clearwater | Florida | United States | 33765 |
| 10 | InVentiv Health | Miami | Florida | United States | 33136 |
| 11 | Omega Research Consultants | Orlando | Florida | United States | 32810 |
| 12 | McIlwain Medical Group | Tampa | Florida | United States | 33613 |
| 13 | Institute of Arthritis Research | Idaho Falls | Idaho | United States | 83404 |
| 14 | Advanced Clinical Research | Meridian | Idaho | United States | 83642 |
| 15 | Medication Management | Greensboro | North Carolina | United States | 27408 |
| 16 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 17 | Clinical Research Center of Reading | Wyomissing | Pennsylvania | United States | 19610 |
| 18 | Metroplex Clinical Research | Dallas | Texas | United States | 75231 |
| 19 | Baylor Research Inst. | Dallas | Texas | United States | 75246 |
| 20 | Accurate Clinical Management - VO | Houston | Texas | United States | 77004 |
| 21 | Accurate Clinical Research | Houston | Texas | United States | 77089 |
| 22 | Crossroads Clinical Research, LLC | Victoria | Texas | United States | 77901 |
| 23 | Danville Orthopedic Clinic, Inc.; Research Department | Danville | Virginia | United States | 24541 |
| 24 | Instituto de Investigaciones Clinicas-Mar del Plata | Buenos Aires | Argentina | B7600FZN | |
| 25 | Organizacion Medica de Investigacion | Buenos Aires | Argentina | C1015ABO | |
| 26 | Hospital Italiano | Buenos Aires | Argentina | C1181ACH | |
| 27 | APRILLUS | Buenos Aires | Argentina | C1194AAO | |
| 28 | Instituto centenario | Buenos Aires | Argentina | C1204AAD | |
| 29 | Centro de Investigacion en Enfermedades Reumaticas CIER | Ciudad Autonoma Buenos Aires | Argentina | C1055AAF | |
| 30 | Expertia S.A- Mautalen Salud e Investigación | Ciudad Autonoma Buenos Aires | Argentina | C1128AAE | |
| 31 | CCBR - Buenos Aires - AR; AxisMed SRL | Ciudad Autonoma Buenos Aires | Argentina | C1430CKE | |
| 32 | ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas | Cordoba | Argentina | X5000BNB | |
| 33 | Hospital Italiano de La Plata | La Plata | Argentina | 1900 | |
| 34 | Centro de Investigaciones Medicas Mar Del Plata | Mar del Plata | Argentina | B7600DHK | |
| 35 | Instituto de Investigaciones Clínicas Quilmes | Quilmes | Argentina | 1878 | |
| 36 | CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica | San Juan | Argentina | 5400 | |
| 37 | Centro Medico Privado de Reumatologia; Reumathology | San Miguel | Argentina | T4000AXL | |
| 38 | CIP - Centro Internacional de Pesquisa; Pesquisa Clinica | Goiânia | GO | Brazil | 74110-120 |
| 39 | Centro Mineiro de Pesquisa - CMIP | Juiz de Fora | MG | Brazil | 36036-330 |
| 40 | Edumed - Educação e Saúde SA | Curitiba | PR | Brazil | 80440-080 |
| 41 | Centro de Estudos em Terapias Inovadoras - CETI | Curtiba | PR | Brazil | 80030-110 |
| 42 | CCBR - Synarc Centro de Pesquisa Clinica - RJ | Rio de Janeiro | RJ | Brazil | 22271-100 |
| 43 | Hospital Sao Vicente de Paulo | Passo Fundo | RS | Brazil | 99010-090 |
| 44 | LMK Serviços Médicos S/S | Porto Alegre | RS | Brazil | 90480-000 |
| 45 | CAEP - Centro Avancado de Estudos e Pesquisas Ltda. | Campinas | SP | Brazil | 13087-567 |
| 46 | Faculdade de Medicina do ABC - FMABC | Santo Andre | SP | Brazil | 09060-650 |
| 47 | Instituto de Pesquisa Clínica e Medicina Avançada Ltda | Sao Paulo | SP | Brazil | 05437-010 |
| 48 | Fundação Faculdade Regional de Medicina de São José do Rio Preto | São José do Rio Preto | SP | Brazil | 15090-000 |
| 49 | CPCLIN - Centro de Pesquisas Clínicas Ltda.; Pesquisa Clinica | São Paulo | SP | Brazil | 01244-030 |
| 50 | MHAT - Dobrich, AD | Dobrich | Bulgaria | 9300 | |
| 51 | MHAT "Eurohospital" - Plovdiv, OOD | Plovdiv | Bulgaria | 4002 | |
| 52 | MHAT Kaspela; EOOD | Plovdiv | Bulgaria | 4002 | |
| 53 | MHAT - Ruse, AD | Ruse | Bulgaria | 7002 | |
| 54 | Medizinski Zentrar-1-Sevlievo EOOD | Sevlievo | Bulgaria | 5400 | |
| 55 | MHAT "Hadzhi Dimitar", OOD | Sliven | Bulgaria | 8800 | |
| 56 | Medical Center Excelsior OOD | Sofia | Bulgaria | 1000 | |
| 57 | NMTH "Tsar Boris III" | Sofia | Bulgaria | 1233 | |
| 58 | MHAT "Lyulin", EAD | Sofia | Bulgaria | 1336 | |
| 59 | DCC "Alexandrovska", EOOD; Clinic of Neurology | Sofia | Bulgaria | 1431 | |
| 60 | UMHAT "SofiaMed", OOD | Sofia | Bulgaria | 1750 | |
| 61 | MC "Synexus - Sofia", EOOD | Sofia | Bulgaria | 1784 | |
| 62 | MHAT Dr. St. Kirkovich, AD | Stara Zagora | Bulgaria | 6003 | |
| 63 | 'New Medical Center' , EOOD | Vratsa | Bulgaria | 3000 | |
| 64 | Centro de Reumatologia y Ortopedia | Barranquilla | Colombia | 80020 | |
| 65 | Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM | Bogota | Colombia | 110221 | |
| 66 | Riesgo de Fractura S.A. | Bogota | Colombia | 110221 | |
| 67 | Fundación Instituto de Reumatología Fernando Chalem | Bogota | Colombia | 111211 | |
| 68 | Clinica de Artritis Temprana S.A. | Cali | Colombia | 00000 | |
| 69 | Hospital Pablo Tobon Uribe | Medellin | Colombia | 050034 | |
| 70 | Chungnam National University Hospital; Department of Internal Medicine (Rheumatology) | Daejeon | Korea, Republic of | 35015 | |
| 71 | Chonnam National University Hospital | Gwangju | Korea, Republic of | 61469 | |
| 72 | Seoul National University Bundang Hospital | Gyeonggi-do | Korea, Republic of | 13620 | |
| 73 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 74 | Konkuk University Medical Center | Seoul | Korea, Republic of | 05030 | |
| 75 | Asan Medical Center - Oncology | Seoul | Korea, Republic of | 05505 | |
| 76 | Ajou University Hospital | Suwon City | Korea, Republic of | 443-721 | |
| 77 | Consultorio Medico en Fundacion el Hospitalito de morelos A.C. | Cuernavaca | Morelos | Mexico | 62170 |
| 78 | Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI) | Culiacán Rosales | Sinaloa | Mexico | 80000 |
| 79 | Centro de Investigacion en Reumatologia | Merida | Yucatan | Mexico | 97070 |
| 80 | Consultorio Particular del Dr. Miguel Cortes Hernandez | Cuernavaca | Mexico | 62290 | |
| 81 | Centro de Investigacion en Enfermedades Reumaticas y Osteoporosis | Mexicali | Mexico | 21100 | |
| 82 | Centro de Investigacion Clínica GRAMEL S.C | Mexico | Mexico | 03720 | |
| 83 | Policilinica Medica de Queretaro; Rheumatology | Queretaro | Mexico | 76000 | |
| 84 | Clinical Research Institute | Tlalnepantla | Mexico | 54055 | |
| 85 | Unidad de Enfermedades Reumaticas y Cronicodegenerativas | Torreon | Mexico | 27000 | |
| 86 | NZOZ OSTEO-MEDIC S.C. Artur Racewicz, Jerzy Supronik | Bialystok | Poland | 15-351 | |
| 87 | Szpital Uniwersytecki; nr 2 im. Dr J. Biziela | Bydgoszcz | Poland | 85-168 | |
| 88 | Medica Pro Familia Spolka Akcyjna Oddzial w Katowicach | Katowice | Poland | 40-081 | |
| 89 | Centrum Medyczne Plejady | Krakow | Poland | 30-349 | |
| 90 | CCBR - Lodz - PL | Lodz | Poland | 90-368 | |
| 91 | ETYKA Osrodek Badan Kliniczynch | Olsztyn | Poland | 10-117 | |
| 92 | Ai Centrum Medyczne Sp. Z O.O Sp.K. | Poznan | Poland | 61-113 | |
| 93 | KO-MED Centra Kliniczne Staszow | Staszow | Poland | 28-200 | |
| 94 | Medycyna Kliniczna | Warszawa | Poland | 00-660 | |
| 95 | Centrum Medyczne AMED | Warszawa | Poland | 03-291 | |
| 96 | Wojewódzki Szpital Specjalistyczny we Wrocławiu | Wrocław | Poland | 51-124 | |
| 97 | KO-MED Centra Kliniczne Zamosc | Zamosc | Poland | 22400 | |
| 98 | TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich | Krasnoyarsk | Krasnojarsk | Russian Federation | 660062 |
| 99 | Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova | Moscow | Moskovskaja Oblast | Russian Federation | 115522 |
| 100 | SBIH of Moscow "City Clinical Hospital # 1 n. a. N. I. Pirogov" | Moscow | Moskovskaja Oblast | Russian Federation | 119049 |
| 101 | SBEI HPE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF | Moscow | Moskovskaja Oblast | Russian Federation | 119992 |
| 102 | Technologii zdorovia LLC | Sankt-peterburg | Sankt Petersburg | Russian Federation | 191144 |
| 103 | Sanavita LLC | Sankt-peterburg | Sankt Petersburg | Russian Federation | 195257 |
| 104 | LLC Medical Sanitary Unit | Sankt-peterburg | Sankt Petersburg | Russian Federation | 196066 |
| 105 | Center of Family Medicine LC | Yekaterinburg | Sankt Petersburg | Russian Federation | 620043 |
| 106 | SBHI of Yaroslavl Region Clinical Hospital #3 | Yaroslavl | Volgograd | Russian Federation | 150051 |
| 107 | SMMIH "Chelyabinsk Regional Clinical Hospital" | Chelyabinsk | Voronez | Russian Federation | 454076 |
| 108 | SAHI of Kem. "Regional Clinical Hospital for War Veterans" | Kemerovo | Russian Federation | 650000 | |
| 109 | OOO Family Polyclinic | Korolev, Moscow Region | Russian Federation | 141060 | |
| 110 | Practical Medicine | Moscow | Russian Federation | 115404 | |
| 111 | Limited Liability Company "Centre of Medical Common Practice" | Novosibirsk | Russian Federation | 630091 | |
| 112 | Ultramed | Omsk | Russian Federation | 644024 | |
| 113 | SBEI HPE "Saratov State Medical University n.a. V. I. Razumovskiy" of the MoH of the RF | Saratov | Russian Federation | 410026 | |
| 114 | SBEI HPE "Smolensk State Medical University" of the MoH of the RF | Smolensk | Russian Federation | 214019 | |
| 115 | City Hospital 25; Rheumatology | St. Petersburg | Russian Federation | 190068 | |
| 116 | Pavlov First Saint Petersburg State Medical University | St. Petersburg | Russian Federation | 197022 | |
| 117 | Siberian State Medical University | Tomsk | Russian Federation | 634050 | |
| 118 | SHI Ulyanovsk Reg Clinical Hospital | Ulyanovsk | Russian Federation | 432063 | |
| 119 | Territorial Clinical Hospital #2 | Vladivostok | Russian Federation | 690035 | |
| 120 | SHI Yaroslavl Regional Clinical Hospital | Yaroslavl | Russian Federation | 150062 | |
| 121 | Institute of Rheumatology | Belgrade | Serbia | 11000 | |
| 122 | Military Medical Academy | Belgrade | Serbia | 11040 | |
| 123 | Clinical Center Kragujevac | Kragujevac | Serbia | 34000 | |
| 124 | Institute of Treatment and Rehabilitation "Niska Banja" | Niska Banja | Serbia | 18205 | |
| 125 | Special hospital for rheumatic diseases Novi Sad | Novi Sad | Serbia | 21000 | |
| 126 | General Hospital Sabac; Department of Urology and Hemodialysis | Sabac | Serbia | 15000 | |
| 127 | CI of TRC | Ternopil | Kherson Governorate | Ukraine | 46002 |
| 128 | Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU | Ivano-Frankivsk | KIEV Governorate | Ukraine | 76008 |
| 129 | Medical Center Medical Clinic Blagomed LLC. | Kyiv | KIEV Governorate | Ukraine | 01601 |
| 130 | Medical Center OK!Clinic+ | Kyiv | KIEV Governorate | Ukraine | 02091 |
| 131 | SI NSС M.D. Strazhesko Institute of Cardiology of NAMSU | Kyiv | KIEV Governorate | Ukraine | 03680 |
| 132 | Clinic of Modern Rheumatology Revmotsentr LLC | Kyiv | KIEV Governorate | Ukraine | 04071 |
| 133 | Lviv Regional Clinical Hospital Dept of Rehmuaatology D. Halytskyi Lviv NMU | Lviv | KIEV Governorate | Ukraine | 79010 |
| 134 | CH of State Border Service of Ukraine (Military Base 2522); Dept of Therapy, D.Halytskyi Lviv NMU | Lviv | KIEV Governorate | Ukraine | 79014 |
| 135 | A.Novak Transcarpathian Regional Clinical Hospital | Uzhgorod | KIEV Governorate | Ukraine | 88018 |
| 136 | Railway Transp DCH of HealthCenter Branch of PJSC Ukr Railway Dept of Rheumatology | Dnipro | Tavria Okruha | Ukraine | 49008 |
| 137 | GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine | Kharkiv | Ukraine | 61039 | |
| 138 | Kharkiv MA of PGE of MOHU Ch of Cardiology and Functional Diagnostics | Kharkiv | Ukraine | 61176 | |
| 139 | CNI Consultative and Diagnostic Center of Desnianskyi District of Kyiv | Kyiv | Ukraine | 02232 | |
| 140 | MI of Helathcare Kyiv RCH P.L. Shupy NMA of PGE | Kyiv | Ukraine | 04107 | |
| 141 | Gerontology Institute of the Ukrainian AMS | Kyiv | Ukraine | 04114 | |
| 142 | Oleksandrivska Clinical Hospital | Kyiv | Ukraine | 1023 | |
| 143 | Volyn Regional Center of Cardiovascular Pathology and Thrombolysis | Lutsk | Ukraine | 43024 | |
| 144 | City Hospital #1 | Mykolaiv | Ukraine | 54003 | |
| 145 | M.V. Sklifosovsky Poltava RCH Dept of Rheumatology HSEIU UMSA | Poltava | Ukraine | 36011 | |
| 146 | Private Small Enterprise Medical Center Pulse | Vinnytsia | Ukraine | 21001 | |
| 147 | M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU | Vinnytsia | Ukraine | 21018 | |
| 148 | City Clinical Hospital #9 Dept of Gastrosurgery SI Zaporizhzhia MA of PGE of MoHU | Zaporizhzhia | Ukraine | 69096 | |
| 149 | CI City Hospital #7 | Zaporizhzhia | Ukraine | 69118 | |
| 150 | CI Zaporizhzhia Regional Clinical Hospital of ZRC | Zaporizhzhia | Ukraine | 69600 |
Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT02833350
Other Study ID Numbers:
- GA29350
- 2016-000335-40
First Posted:
Jul 14, 2016
Last Update Posted:
Jun 12, 2020
Last Verified:
Jun 1, 2020
Study Results
Participant Flow
| Recruitment Details | 578 participants were enrolled in the study and 578 were dosed. One (1) subject in Cohort 2 in the Placebo arm was incorrectly dosed with the High Dose. The ITT data set included participants according to their randomization while SAF data set included participants according to the treatment administered. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Period Title: Overall Study | |||||||
| STARTED | 40 | 109 | 110 | 110 | 111 | 49 | 49 |
| Randomized | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| COMPLETED | 37 | 100 | 102 | 102 | 108 | 48 | 44 |
| NOT COMPLETED | 3 | 9 | 8 | 8 | 3 | 1 | 5 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Total of all reporting groups |
| Overall Participants | 40 | 109 | 110 | 110 | 111 | 49 | 49 | 578 |
| Age (Count of Participants) | ||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
35
87.5%
|
95
87.2%
|
99
90%
|
98
89.1%
|
98
88.3%
|
41
83.7%
|
40
81.6%
|
506
87.5%
|
| >=65 years |
5
12.5%
|
14
12.8%
|
11
10%
|
12
10.9%
|
13
11.7%
|
8
16.3%
|
9
18.4%
|
72
12.5%
|
| Age (Years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [Years] |
52.3
(12.0)
|
50.4
(11.0)
|
49.9
(12.4)
|
50.2
(11.6)
|
49.9
(12.4)
|
51.3
(13.2)
|
54.6
(11.5)
|
50.7
(12.0)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
35
87.5%
|
92
84.4%
|
85
77.3%
|
90
81.8%
|
87
78.4%
|
37
75.5%
|
37
75.5%
|
463
80.1%
|
| Male |
5
12.5%
|
17
15.6%
|
25
22.7%
|
20
18.2%
|
24
21.6%
|
12
24.5%
|
12
24.5%
|
115
19.9%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||
| American Indian or Alaska native |
0
0%
|
8
7.3%
|
12
10.9%
|
11
10%
|
9
8.1%
|
6
12.2%
|
5
10.2%
|
51
8.8%
|
| Asian |
1
2.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.2%
|
| Black of African American |
0
0%
|
1
0.9%
|
2
1.8%
|
3
2.7%
|
1
0.9%
|
1
2%
|
2
4.1%
|
10
1.7%
|
| White |
36
90%
|
96
88.1%
|
96
87.3%
|
95
86.4%
|
99
89.2%
|
42
85.7%
|
42
85.7%
|
506
87.5%
|
| Multiple |
3
7.5%
|
2
1.8%
|
0
0%
|
1
0.9%
|
1
0.9%
|
0
0%
|
0
0%
|
7
1.2%
|
| Unknown |
0
0%
|
2
1.8%
|
0
0%
|
0
0%
|
1
0.9%
|
0
0%
|
0
0%
|
3
0.5%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||||||
| Hispanic or Latino |
8
20%
|
38
34.9%
|
40
36.4%
|
38
34.5%
|
39
35.1%
|
17
34.7%
|
15
30.6%
|
195
33.7%
|
| Not Hispanic or Latino |
31
77.5%
|
68
62.4%
|
69
62.7%
|
72
65.5%
|
70
63.1%
|
32
65.3%
|
33
67.3%
|
375
64.9%
|
| Not Stated |
0
0%
|
1
0.9%
|
1
0.9%
|
0
0%
|
0
0%
|
0
0%
|
1
2%
|
3
0.5%
|
| Unknown |
1
2.5%
|
2
1.8%
|
0
0%
|
0
0%
|
2
1.8%
|
0
0%
|
0
0%
|
5
0.9%
|
Outcome Measures
| Title | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1) |
|---|---|
| Description | ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 |
| Number (95% Confidence Interval) [Percentage] |
17.5
|
27.5
|
34.5
|
14.5
|
36.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2503 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted difference |
| Estimated Value | 8.00 | |
| Confidence Interval |
(2-Sided) 95% -5.64 to 21.64 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0164 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted difference |
| Estimated Value | 12.93 | |
| Confidence Interval |
(2-Sided) 95% 2.37 to 23.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted difference |
| Estimated Value | 20.00 | |
| Confidence Interval |
(2-Sided) 95% 9.21 to 30.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Adverse Events |
|---|---|
| Description | An Adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE was any experience that suggested a significant hazard, contraindication, side effect or precaution that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. |
| Time Frame | Day 1 up to 8 weeks after last dose (up to Week 20) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all participants according to treatment administered. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 49 | 49 |
| Number [Percentage] |
37.5
|
42.2
|
50.9
|
45.5
|
45.0
|
22.4
|
44.9
|
| Title | Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1) |
|---|---|
| Description | ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 |
| Number (95% Confidence Interval) [Percentage] |
17.5
|
27.5
|
34.5
|
14.5
|
36.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1694 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted difference |
| Estimated Value | -8.58 | |
| Confidence Interval |
(2-Sided) 95% -20.82 to 3.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8132 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted difference |
| Estimated Value | -1.50 | |
| Confidence Interval |
() 95% -13.96 to 10.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2) |
|---|---|
| Description | ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Arm/Group Description | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 48 | 50 |
| Number (95% Confidence Interval) [Percentage] |
25.0
|
12.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0717 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Weighted difference |
| Estimated Value | 13.7 | |
| Confidence Interval |
(2-Sided) 95% -1.21 to 28.61 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response |
|---|---|
| Description | ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate] |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
10.0
|
14.7
|
13.6
|
10.0
|
25.2
|
22.9
|
2.0
|
| Week 2 Day 14 |
12.5
|
19.3
|
27.3
|
16.4
|
48.6
|
25.0
|
10.0
|
| Week 4 Day 28 |
30.0
|
34.9
|
41.8
|
25.5
|
59.5
|
35.4
|
24.0
|
| Week 8 Day 56 |
50.0
|
52.3
|
58.2
|
37.3
|
71.2
|
47.9
|
18.0
|
| Week 12 Day 84 |
60.0
|
56.0
|
59.1
|
36.4
|
72.1
|
58.3
|
24.0
|
| Title | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response |
|---|---|
| Description | ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
2.5
|
2.8
|
3.6
|
2.7
|
4.5
|
6.3
|
2.0
|
| Week 2 Day 14 |
0.0
|
1.8
|
7.3
|
2.7
|
9.0
|
10.4
|
0.00
|
| Week 4 day 28 |
5.0
|
9.2
|
10.0
|
6.4
|
25.2
|
10.4
|
6.0
|
| Week 8 Day 56 |
15.0
|
18.3
|
22.7
|
17.3
|
32.4
|
22.9
|
10.0
|
| Week 12 Day 84 |
17.5
|
27.5
|
34.5
|
14.5
|
36.0
|
25.0
|
12.0
|
| Title | Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response |
|---|---|
| Description | ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
0.0
|
0.9
|
0.9
|
0.0
|
0.0
|
0.0
|
0.0
|
| Week 2 Day 14 |
0.0
|
0.9
|
0.0
|
0.00
|
3.6
|
4.2
|
0.0
|
| Week 4 Day 28 |
0
|
2.8
|
4.5
|
0.9
|
6.3
|
2.1
|
2.0
|
| Week 8 Day 56 |
0.0
|
7.3
|
9.1
|
3.6
|
14.4
|
6.3
|
4.0
|
| Week 12 Day 84 |
5.0
|
9.2
|
12.7
|
7.3
|
18.0
|
14.6
|
4.0
|
| Title | Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) |
|---|---|
| Description | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-0.34
(0.60)
|
-0.35
(0.66)
|
-0.37
(0.80)
|
-0.33
(0.84)
|
-0.92
(0.71)
|
-0.49
(0.84)
|
-0.36
(0.63)
|
| Week 2 Day 14 |
-0.47
(0.72)
|
-0.63
(0.84)
|
-0.70
(0.80)
|
-.54
(0.90)
|
-1.09
(0.81)
|
-0.65
(0.87)
|
-0.45
(0.69)
|
| Week 4 Day 28 |
-0.75
(0.86)
|
-0.90
(0.96)
|
-0.91
(0.97)
|
-0.62
(1.04)
|
-1.45
(0.87)
|
-0.77
(0.90)
|
-0.44
(0.84)
|
| Week 8 Day 56 |
-1.14
(0.90)
|
-1.35
(1.12)
|
-1.37
(1.11)
|
-1.08
(1.19)
|
-1.75
(0.98)
|
-1.33
(0.98)
|
-0.56
(0.87)
|
| Week 12 Day 84 |
-1.30
(0.95)
|
-1.72
(1.11)
|
-1.70
(1.02)
|
-1.17
(1.24)
|
-1.87
(1.02)
|
-1.62
(1.15)
|
-0.86
(1.03)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8504 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | adjusted difference |
| Estimated Value | -0.11 | |
| Confidence Interval |
(2-Sided) 95% -0.45 to 0.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | At week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9884 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.28 to 0.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1 Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9230 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.31 to 0.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9853 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.43 to 0.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6826 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.38 to 0.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2634 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.18 | |
| Confidence Interval |
(2-Sided) 95% -0.45 to 0.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2885 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.29 | |
| Confidence Interval |
(2-Sided) 95% -0.72 to 0.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0598 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.30 | |
| Confidence Interval |
(2-Sided) 95% -0.61 to 0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0440 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.62 to -0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4271 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.76 to 0.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0969 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.66 to 0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0612 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.33 | |
| Confidence Interval |
(2-Sided) 95% -0.68 to 0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2079 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.36 | |
| Confidence Interval |
(2-Sided) 95% -0.84 to 0.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.57 | |
| Confidence Interval |
(2-Sided) 95% -0.92 to -0.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.57 | |
| Confidence Interval |
(2-Sided) 95% -0.92 to -0.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.58 | |
| Confidence Interval |
(2-Sided) 95% 0.34 to 0.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.55 | |
| Confidence Interval |
(2-Sided) 95% 0.31 to 0.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.47 | |
| Confidence Interval |
(2-Sided) 95% 0.20 to 0.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.40 | |
| Confidence Interval |
(2-Sided) 95% 0.13 to 0.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.56 | |
| Confidence Interval |
(2-Sided) 95% 0.25 to 0.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.55 | |
| Confidence Interval |
(2-Sided) 95% 0.24 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0095 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.42 | |
| Confidence Interval |
(2-Sided) 95% 0.08 to 0.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0153 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.40 | |
| Confidence Interval |
(2-Sided) 95% 0.06 to 0.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4839 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.19 | |
| Confidence Interval |
(2-Sided) 95% -0.16 to 0.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5035 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.19 | |
| Confidence Interval |
(2-Sided) 95% -0.16 to 0.53 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4286 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.11 | |
| Confidence Interval |
(2-Sided) 95% -0.38 to 0.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1831 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.20 | |
| Confidence Interval |
(2-Sided) 95% -0.50 to 0.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0667 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.65 to 0.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.77 | |
| Confidence Interval |
(2-Sided) 95% -1.11 to -0.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.76 | |
| Confidence Interval |
(2-Sided) 95% -1.15 to -0.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) |
|---|---|
| Description | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-0.43
(0.67)
|
-0.48
(0.73)
|
-0.49
(0.86)
|
-0.37
(0.91)
|
-1.10
(0.75)
|
-0.63
(0.91)
|
-.40
(0.69)
|
| Week 2 Day 14 |
-0.51
(0.85)
|
-0.77
(0.86)
|
-0.84
(0.86)
|
-0.57
(1.00)
|
-1.26
(0.89)
|
-0.81
(0.98)
|
-0.54
(0.80)
|
| Week 4 Day 28 |
-0.88
(0.90)
|
-1.06
(1.02)
|
-1.08
(1.03)
|
-0.65
(1.16)
|
-1.61
(0.94)
|
-0.95
(1.04)
|
-0.55
(0.94)
|
| Week 8 Day 56 |
-1.31
(0.91)
|
-1.56
(1.21)
|
-1.57
(1.16)
|
1.20
(1.30)
|
-1.97
(1.03)
|
-1.51
(1.05)
|
-0.67
(1.01)
|
| Week 12 Day 84 |
-1.53
(0.95)
|
-1.97
(1.20)
|
-1.93
(1.11)
|
-1.33
(1.33)
|
-2.06
(1.08)
|
-1.83
(1.22)
|
-1.00
(1.11)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5807 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.18 | |
| Confidence Interval |
(2-Sided) 95% -0.55 to 0.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6270 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.12 | |
| Confidence Interval |
(2-Sided) 95% -0.39 to 0.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4475 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.42 to 0.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9891 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.47 to 0.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2244 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.21 | |
| Confidence Interval |
(2-Sided) 95% -0.51 to 0.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0586 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.58 to 0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1338 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.39 | |
| Confidence Interval |
(2-Sided) 95% -0.85 to 0.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0119 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 95% -0.74 to -0.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0046 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.44 | |
| Confidence Interval |
(2-Sided) 95% -0.77 to -0.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3943 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.82 to 0.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0526 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.37 | |
| Confidence Interval |
(2-Sided) 95% -0.74 to 0.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0365 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.39 | |
| Confidence Interval |
(2-Sided) 95% -0.76 to -0.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1696 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.41 | |
| Confidence Interval |
(2-Sided) 95% -0.93 to 0.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.63 | |
| Confidence Interval |
(2-Sided) 95% -1.01 to -0.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.62 | |
| Confidence Interval |
(2-Sided) 95% -1.00 to -0.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.64 | |
| Confidence Interval |
(2-Sided) 95% 0.37 to 0.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.61 | |
| Confidence Interval |
(2-Sided) 95% 0.34 to 0.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) 95% 0.21 to 0.79 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0012 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.43 | |
| Confidence Interval |
(2-Sided) 95% 0.14 to 0.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.58 | |
| Confidence Interval |
(2-Sided) 95% 0.25 to 0.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.54 | |
| Confidence Interval |
(2-Sided) 95% 0.21 to 0.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0084 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.46 | |
| Confidence Interval |
(2-Sided) 95% 0.09 to 0.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0124 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.44 | |
| Confidence Interval |
(2-Sided) 95% 0.07 to 0.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7565 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.15 | |
| Confidence Interval |
(2-Sided) 95% -0.23 to 0.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7158 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.16 | |
| Confidence Interval |
(2-Sided) 95% -0.22 to 0.53 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1368 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.22 | |
| Confidence Interval |
(2-Sided) 95% -0.52 to 0.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0974 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.62 to 0.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0479 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.38 | |
| Confidence Interval |
(2-Sided) 95% -0.76 to -0.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.84 | |
| Confidence Interval |
(2-Sided) 95% -1.22 to -0.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.83 | |
| Confidence Interval |
(2-Sided) 95% -1.24 to -0.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR]) |
|---|---|
| Description | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-0.35
(0.57)
|
-0.42
(0.65)
|
-0.39
(0.68)
|
-0.34
(0.86)
|
-0.72
(0.72)
|
-0.50
(0.73)
|
-0.31
(0.60)
|
| Week 2 Day 14 |
-0.60
(0.89)
|
-0.69
(0.84)
|
-0.68
(0.74)
|
-0.55
(0.92)
|
-1.02
(0.84)
|
-0.64
(0.81)
|
-0.51
(0.73)
|
| Week 4 Day 28 |
-0.88
(0.89)
|
-0.99
(0.98)
|
-0.97
(0.90)
|
-0.75
(1.02)
|
-1.47
(1.02)
|
-0.85
(0.81)
|
-0.50
(0.83)
|
| Week 8 Day 56 |
-1.25
(0.85)
|
-1.44
(1.14)
|
-1.40
(1.06)
|
-1.15
(1.19)
|
-1.74
(0.98)
|
-1.35
(0.96)
|
-0.70
(0.98)
|
| Week 12 Day 84 |
-1.51
(1.01)
|
-1.80
(1.25)
|
-1.80
(0.99)
|
-1.30
(1.22)
|
-1.85
(1.06)
|
-1.65
(1.06)
|
-0.94
(10.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9193 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.41 to 0.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7062 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.10 | |
| Confidence Interval |
(2-Sided) 95% -0.33 to 0.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8542 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.31 to 0.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8095 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.13 | |
| Confidence Interval |
(2-Sided) 95% -0.51 to 0.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3862 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.17 | |
| Confidence Interval |
(2-Sided) 95% -0.44 to 0.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4328 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.16 | |
| Confidence Interval |
(2-Sided) 95% -0.43 to 0.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4915 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.24 | |
| Confidence Interval |
(2-Sided) 95% -0.68 to 0.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1441 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.26 | |
| Confidence Interval |
(2-Sided) 95% -0.58 to 0.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1890 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.24 | |
| Confidence Interval |
(2-Sided) 95% -0.56 to 0.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5566 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.25 | |
| Confidence Interval |
(2-Sided) 95% -0.74 to -0.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0920 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.32 | |
| Confidence Interval |
(2-Sided) 95% -0.68 to 0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1391 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.29 | |
| Confidence Interval |
(2-Sided) 95% -0.65 to 0.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2873 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.35 | |
| Confidence Interval |
(2-Sided) 95% -0.86 to 0.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0020 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.54 | |
| Confidence Interval |
(2-Sided) 95% -0.91 to -0.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0016 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.54 | |
| Confidence Interval |
(2-Sided) 95% -0.92 to -0.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0050 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.31 | |
| Confidence Interval |
(2-Sided) 95% 0.07 to 0.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0020 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.33 | |
| Confidence Interval |
(2-Sided) 95% 0.10 to 0.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0082 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.35 | |
| Confidence Interval |
(2-Sided) 95% 0.07 to 0.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0056 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.35 | |
| Confidence Interval |
(2-Sided) 95% 0.08 to 0.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.50 | |
| Confidence Interval |
(2-Sided) 95% 0.19 to 0.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.52 | |
| Confidence Interval |
(2-Sided) 95% 0.21 to 0.84 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0650 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.34 | |
| Confidence Interval |
(2-Sided) 95% -0.01 to 0.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0365 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.37 | |
| Confidence Interval |
(2-Sided) 95% 0.02 to 0.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9338 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.28 to 0.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9520 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.29 to 0.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1496 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.19 | |
| Confidence Interval |
(2-Sided) 95% -0.45 to 0.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3936 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.13 | |
| Confidence Interval |
(2-Sided) 95% -0.43 to 0.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0346 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.35 | |
| Confidence Interval |
(2-Sided) 95% -0.68 to -0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.68 | |
| Confidence Interval |
(2-Sided) 95% -1.04 to -0.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.73 | |
| Confidence Interval |
(2-Sided) 95% -1.11 to -0.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) |
|---|---|
| Description | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-0.45
(0.63)
|
-0.54
(0.72)
|
-0.52
(0.77)
|
-0.37
(0.95)
|
-0.93
(0.76)
|
-0.65
(0.80)
|
-0.36
(0.66)
|
| Week 2 Day 14 |
-0.63
(0.98)
|
-0.85
(0.85)
|
-0.84
(0.82)
|
-0.58
(1.03)
|
-1.22
(0.94)
|
-0.81
(0.92)
|
-0.60
(0.84)
|
| Week 4 Day 28 |
-1.00
(0.95)
|
-1.16
(1.06)
|
-1.15
(0.98)
|
-0.79
(1.16)
|
-1.65
(1.11)
|
-1.04
(0.95)
|
-0.61
(0.96)
|
| Week 8 Day 56 |
-1.43
(0.88)
|
-1.67
(1.25)
|
-1.63
(1.14)
|
-1.29
(1.31)
|
-2.00
(1.06)
|
-1.54
(1.04)
|
-0.81
(1.12)
|
| Week 12 Day 84 |
-1.76
(1.04)
|
-2.06
(1.36)
|
-2.05
(1.08)
|
-1.46
(1.32)
|
-2.08
(1.14)
|
-1.89
(1.15)
|
-1.08
(1.17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6083 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.17 | |
| Confidence Interval |
(2-Sided) 95% -0.53 to 0.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2672 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.18 | |
| Confidence Interval |
(2-Sided) 95% -0.44 to 0.08 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3158 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.17 | |
| Confidence Interval |
(2-Sided) 95% -0.43 to 0.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8495 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.14 | |
| Confidence Interval |
(2-Sided) 95% -0.55 to 0.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0856 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.58 to 0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1021 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.27 | |
| Confidence Interval |
(2-Sided) 95% -0.57 to 0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2762 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.33 | |
| Confidence Interval |
(2-Sided) 95% -0.82 to 0.15 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0286 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.38 | |
| Confidence Interval |
(2-Sided) 95% -0.73 to -0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0274 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.38 | |
| Confidence Interval |
(2-Sided) 95% -0.73 to -0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4981 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.81 to 0.24 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0472 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.39 | |
| Confidence Interval |
(2-Sided) 95% -0.78 to -0.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0753 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.36 | |
| Confidence Interval |
(2-Sided) 95% -0.75 to 0.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1853 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.43 | |
| Confidence Interval |
(2-Sided) 95% -0.99 to 0.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.62 | |
| Confidence Interval |
(2-Sided) 95% -1.03 to -0.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.62 | |
| Confidence Interval |
(2-Sided) 95% -1.03 to -0.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0005 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.41 | |
| Confidence Interval |
(2-Sided) 95% 0.15 to 0.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.42 | |
| Confidence Interval |
(2-Sided) 95% 0.16 to 0.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0060 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.39 | |
| Confidence Interval |
(2-Sided) 95% 0.09 to 0.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0039 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.40 | |
| Confidence Interval |
(2-Sided) 95% 0.10 to 0.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.53 | |
| Confidence Interval |
(2-Sided) 95% 0.18 to 0.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.53 | |
| Confidence Interval |
(2-Sided) 95% 0.19 to 0.88 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0450 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.39 | |
| Confidence Interval |
(2-Sided) 95% 0.01 to 0.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0259 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.42 | |
| Confidence Interval |
(2-Sided) 95% 0.04 to 0.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9881 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.34 to 0.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9891 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.06 | |
| Confidence Interval |
(2-Sided) 95% -0.34 to 0.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0463 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.29 | |
| Confidence Interval |
(2-Sided) 95% -0.57 to -0.00 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1867 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.23 | |
| Confidence Interval |
(2-Sided) 95% -0.56 to 0.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0213 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.44 | |
| Confidence Interval |
(2-Sided) 95% -0.81 to -0.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8. Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.78 | |
| Confidence Interval |
(2-Sided) 95% -1.19 to -0.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.82 | |
| Confidence Interval |
(2-Sided) 95% -1.24 to -0.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With DAS Low Disease Activity |
|---|---|
| Description | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2 |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
0.0
0%
|
0.9
0.8%
|
1.8
1.6%
|
0.0
0%
|
1.8
1.6%
|
2.1
4.3%
|
0.0
0%
|
| Week 2 day 14 |
0.0
0%
|
0.0
0%
|
1.8
1.6%
|
0.9
0.8%
|
4.5
4.1%
|
2.1
4.3%
|
2.0
4.1%
|
| Week 4 Day 28 |
0.0
0%
|
1.8
1.7%
|
6.4
5.8%
|
1.8
1.6%
|
11.7
10.5%
|
2.1
4.3%
|
0.0
0%
|
| Week 8 Day 56 |
0.0
0%
|
8.3
7.6%
|
11.8
10.7%
|
3.6
3.3%
|
18.0
16.2%
|
2.1
4.3%
|
2.0
4.1%
|
| Week 12 Day 84 |
7.5
18.8%
|
19.3
17.7%
|
14.5
13.2%
|
3.6
3.3%
|
17.1
15.4%
|
14.6
29.8%
|
4.0
8.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.48 to 4.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3482 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 1.82 | |
| Confidence Interval |
(2-Sided) 95% -1.98 to 5.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8979 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 95% -6.51 to 5.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.91 | |
| Confidence Interval |
(2-Sided) 95% -4.30 to 2.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6546 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -3.07 to 4.89 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4 Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7988 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.80 | |
| Confidence Interval |
(2-Sided) 95% -6.95 to 5.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4 Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9975 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.01 | |
| Confidence Interval |
(2-Sided) 95% -4.35 to 4.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1185 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.55 | |
| Confidence Interval |
(2-Sided) 95% -1.16 to 10.25 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4765 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.40 | |
| Confidence Interval |
(2-Sided) 95% -9.01 to 4.21 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1655 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.61 | |
| Confidence Interval |
(2-Sided) 95% -1.90 to 11.12 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0234 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 8.18 | |
| Confidence Interval |
(2-Sided) 95% 1.11 to 15.26 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5490 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.20 | |
| Confidence Interval |
(2-Sided) 95% -7.27 to 13.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 15.62 | |
| Confidence Interval |
(2-Sided) 95% 7.22 to 24.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0044 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 10.91 | |
| Confidence Interval |
(2-Sided) 95% 3.39 to 18.43 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6588 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.05 | |
| Confidence Interval |
(2-Sided) 95% -7.07 to 11.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8853 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.68 | |
| Confidence Interval |
(2-Sided) 95% -8.62 to 9.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6564 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.05 | |
| Confidence Interval |
(2-Sided) 95% -7.00 to 11.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8853 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.68 | |
| Confidence Interval |
(2-Sided) 95% -8.62 to 9.99 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0584 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 11.64 | |
| Confidence Interval |
(2-Sided) 95% -0.41 to 23.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With DAS Remission |
|---|---|
| Description | The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6 |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
2.1
4.3%
|
0.0
0%
|
| Week 2 Day 14 |
0.0
0%
|
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
0.9
0.8%
|
0.00
0%
|
0.0
0%
|
| Week 4 Day 28 |
0.0
0%
|
0.0
0%
|
1.8
1.6%
|
0.9
0.8%
|
4.5
4.1%
|
0.00
0%
|
0.0
0%
|
| Week 8 Day 56 |
0.0
0%
|
3.7
3.4%
|
4.5
4.1%
|
1.8
1.6%
|
9.0
8.1%
|
0.00
0%
|
0.0
0%
|
| Week 12 Day 84 |
2.5
6.3%
|
7.3
6.7%
|
8.2
7.5%
|
3.6
3.3%
|
9.0
8.1%
|
4.2
8.6%
|
4.0
8.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.92 to 2.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.91 to 2.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.92 to 2.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.47 to 4.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8979 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 95% -6.51 to 5.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4 Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.91 | |
| Confidence Interval |
(2-Sided) 95% -4.30 to 2.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6669 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -3.23 to 5.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6309 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -1.60 | |
| Confidence Interval |
(2-Sided) 95% -8.13 to 4.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4473 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 1.83 | |
| Confidence Interval |
(2-Sided) 95% -2.90 to 6.56 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3021 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.73 | |
| Confidence Interval |
(2-Sided) 95% -2.45 to 7.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7134 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -1.60 | |
| Confidence Interval |
(2-Sided) 95% -10.14 to 6.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2635 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.70 | |
| Confidence Interval |
(2-Sided) 95% -2.79 to 10.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1749 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.55 | |
| Confidence Interval |
(2-Sided) 95% -2.02 to 11.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6588 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.05 | |
| Confidence Interval |
(2-Sided) 95% -7.07 to 11.18 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2 Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.31 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.31 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.31 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7848 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 1.37 | |
| Confidence Interval |
(2-Sided) 95% -8.46 to 11.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Meeting the Boolean-based Remission Criteria |
|---|---|
| Description | Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale). |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
0.0
0%
|
0.9
0.8%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Week 2 Day 14 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Week 4 Day 28 |
0.0
0%
|
1.0
0.9%
|
0.0
0%
|
0.9
0.8%
|
2.8
2.5%
|
2.1
4.3%
|
0.0
0%
|
| Week 8 Day 56 |
0.0
0%
|
2.0
1.8%
|
1.90
1.7%
|
1.0
0.9%
|
3.7
3.3%
|
0.0
0%
|
0.0
0%
|
| Week 12 Day 84 |
0.0
0%
|
2.0
1.8%
|
4.1
3.7%
|
1.0
0.9%
|
6.5
5.9%
|
8.5
17.3%
|
0.0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.28 to 6.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5941 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.93 | |
| Confidence Interval |
(2-Sided) 95% -2.50 to 4.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.93 to 2.93 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.17 to 6.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.95 to 2.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.92 to 2.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8929 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.43 | |
| Confidence Interval |
(2-Sided) 95% -6.62 to 5.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9424 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.13 | |
| Confidence Interval |
(2-Sided) 95% -3.78 to 3.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5927 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.94 | |
| Confidence Interval |
(2-Sided) 95% -4.40 to 2.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8788 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.46 | |
| Confidence Interval |
(2-Sided) 95% -6.31 to 5.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8 Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6876 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% -3.36 to 5.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6656 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.97 | |
| Confidence Interval |
(2-Sided) 95% -3.42 to 5.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12 Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8787 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.46 | |
| Confidence Interval |
(2-Sided) 95% -6.34 to 5.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7101 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% -3.17 to 4.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2425 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.20 | |
| Confidence Interval |
(2-Sided) 95% -2.16 to 8.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.68 to 8.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2 Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.39 to 8.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6658 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.03 | |
| Confidence Interval |
(2-Sided) 95% -7.17 to 11.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.77 to 8.77 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2457 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 6.57 | |
| Confidence Interval |
(2-Sided) 95% -4.52 to 17.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Clinical Disease Activity Index (CDAI) |
|---|---|
| Description | CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest. Negative values indicate improvement/reduction in RA disease activity. |
| Time Frame | Baseline, Days 7, 14, 28, 56 and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-5.45
(7.69)
|
-6.70
(8.26)
|
-7.40
(9.97)
|
-4.71
(12.91)
|
-9.64
(8.93)
|
-8.61
(10.67)
|
-5.26
(9.79)
|
| Week 2 Day 14 |
-6.85
(11.10)
|
-10.33
(10.45)
|
-11.33
(10.47)
|
-7.44
(13.39)
|
-13.44
(10.52)
|
-9.64
(12.17)
|
-7.70
(10.64)
|
| Week 4 Day 28 |
-10.36
(10.88)
|
-13.84
(12.11)
|
-13.78
(11.46)
|
-9.43
(14.77)
|
-17.74
(10.84)
|
-11.83
(11.08)
|
-7.49
(11.46)
|
| Week 8 Day 56 |
-14.76
(10.04)
|
-18.61
(13.48)
|
-18.10
(12.99)
|
-15.49
(15.74)
|
-21.36
(11.69)
|
-17.38
(12.39)
|
-7.57
(10.51)
|
| Week 12 Day 84 |
-16.99
(11.21)
|
-22.05
(12.19)
|
-22.10
(11.83)
|
-17.02
(16.24)
|
-22.22
(11.76)
|
-20.42
(13.20)
|
-12.23
(12.06)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4960 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.36 | |
| Confidence Interval |
(2-Sided) 95% -6.73 to 2.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2736 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.18 | |
| Confidence Interval |
(2-Sided) 95% -5.34 to 0.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0608 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.08 | |
| Confidence Interval |
(2-Sided) 95% -6.26 to 0.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9237 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -1.25 | |
| Confidence Interval |
(2-Sided) 95% -6.02 to 3.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0893 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.14 | |
| Confidence Interval |
(2-Sided) 95% -6.60 to 0.33 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0138 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -4.07 | |
| Confidence Interval |
(2-Sided) 95% -7.51 to -0.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3358 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.22 | |
| Confidence Interval |
(2-Sided) 95% -8.24 to 1.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0078 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -4.57 | |
| Confidence Interval |
(2-Sided) 95% -8.20 to -0.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0059 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -4.68 | |
| Confidence Interval |
(2-Sided) 95% -8.30 to -1.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6503 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.29 | |
| Confidence Interval |
(2-Sided) 95% -7.39 to 2.80 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1282 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.12 | |
| Confidence Interval |
(2-Sided) 95% -6.84 to 0.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1675 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.94 | |
| Confidence Interval |
(2-Sided) 95% -6.65 to 0.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4220 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.94 | |
| Confidence Interval |
(2-Sided) 95% -7.96 to 2.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0027 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -5.10 | |
| Confidence Interval |
(2-Sided) 95% -8.77 to -1.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0011 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -5.47 | |
| Confidence Interval |
(2-Sided) 95% -9.15 to -1.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0455 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.21 | |
| Confidence Interval |
(2-Sided) 95% 0.05 to 6.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2309 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.31 | |
| Confidence Interval |
(2-Sided) 95% -0.87 to 5.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0698 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.27 | |
| Confidence Interval |
(2-Sided) 95% -0.18 to 6.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2851 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.33 | |
| Confidence Interval |
(2-Sided) 95% -1.09 to 5.76 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0131 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.29 | |
| Confidence Interval |
(2-Sided) 95% 0.69 to 7.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0161 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.18 | |
| Confidence Interval |
(2-Sided) 95% 0.59 to 7.78 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0360 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.85 | |
| Confidence Interval |
(2-Sided) 95% 0.18 to 7.51 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0252 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.04 | |
| Confidence Interval |
(2-Sided) 95% 0.37 to 7.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9032 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 1.03 | |
| Confidence Interval |
(2-Sided) 95% -2.59 to 4.66 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9791 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.66 | |
| Confidence Interval |
(2-Sided) 95% -2.97 to 4.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0927 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.22 | |
| Confidence Interval |
(2-Sided) 95% -6.98 to 0.54 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3202 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.12 | |
| Confidence Interval |
(2-Sided) 95% -6.33 to 2.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0476 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -4.20 | |
| Confidence Interval |
(2-Sided) 95% -8.36 to -0.04 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 54 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -9.93 | |
| Confidence Interval |
(2-Sided) 95% -14.31 to -5.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -8.23 | |
| Confidence Interval |
(2-Sided) 95% -12.56 to -3.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Meeting the CDAI-based Remission Criteria |
|---|---|
| Description | Clinical Disease Activity Index is defined as CDAI= : SJC(28) + TJC(28) + PGA + MDG where TJC and SJC are the tender and swollen joint counts from 28 joints, PGA is the patient's global assessment of disease activity (on a 0-10 scale) and MDG is physician global assessment of disease activity (on a 0-10 scale). The cutoff value for CDAI remission is <=2.8. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
0.0
0%
|
0.9
0.8%
|
0.9
0.8%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Week 2 Day 14 |
0.0
0%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
1.8
1.6%
|
0.0
0%
|
0.0
0%
|
| Week 4 Day 28 |
0.0
0%
|
0.9
0.8%
|
0.9
0.8%
|
0.0
0%
|
4.5
4.1%
|
2.1
4.3%
|
0.0
0%
|
| Week 8 Day 56 |
0.0
0%
|
2.8
2.6%
|
5.5
5%
|
0.00
0%
|
7.2
6.5%
|
4.2
8.6%
|
0.0
0%
|
| Week 12 Day 84 |
0.0
0%
|
5.5
5%
|
6.4
5.8%
|
0.9
0.8%
|
9.9
8.9%
|
6.3
12.9%
|
6.0
12.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.48 to 4.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.47 to 4.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.92 to 2.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.91 to 2.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5726 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.26 to 4.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.47 to 4.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1446 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.74 | |
| Confidence Interval |
(2-Sided) 95% -0.94 to 6.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0286 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 5.45 | |
| Confidence Interval |
(2-Sided) 95% 0.57 to 10.34 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8979 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 95% -6.51 to 5.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0708 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.57 | |
| Confidence Interval |
(2-Sided) 95% -0.39 to 9.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0478 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 5.45 | |
| Confidence Interval |
(2-Sided) 95% 0.05 to 10.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.31 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.31 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6564 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.05 | |
| Confidence Interval |
(2-Sided) 95% -7.00 to 11.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3838 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.11 | |
| Confidence Interval |
(2-Sided) 95% -5.14 to 13.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9009 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.68 | |
| Confidence Interval |
(2-Sided) 95% -10.10 to 11.47 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Simplified Disease Activity Index (SDAI) |
|---|---|
| Description | Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity |
| Time Frame | Baseline, Days 7, 14, 28, 56 and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-5.36
(7.86)
|
-6.48
(8.87)
|
-6.99
(10.49)
|
-4.75
(13.25)
|
-10.86
(9.33)
|
-8.73
(11.21)
|
-5.37
(9.49)
|
| Week 2 Day 14 |
-6.50
(10.54)
|
-10.46
(10.97)
|
-11.44
(10.85)
|
-7.54
(13.74)
|
-14.39
(10.99)
|
-9.84
(12.29)
|
-8.13
(11.01)
|
| Week 4 Day 28 |
-10.53
(11.03)
|
-14.47
(12.41)
|
-14.21
(12.20)
|
-8.92
(15.17)
|
-18.87
(11.20)
|
-12.13
(11.13)
|
-7.74
(12.02)
|
| Week 8 Day 56 |
-15.25
(10.41)
|
-18.95
(13.80)
|
-18.97
(13.91)
|
-15.74
(16.18)
|
-22.62
(11.97)
|
-18.57
(12.80)
|
-7.82
(11.20)
|
| Week 12 Day 84 |
-17.54
(11.36)
|
-22.89
(12.52)
|
-23.24
(12.50)
|
-17.47
(16.70)
|
-23.33
(11.97)
|
-21.97
(13.78)
|
-12.92
(12.61)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5455 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.36 | |
| Confidence Interval |
(2-Sided) 95% -7.00 to 2.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4114 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -1.97 | |
| Confidence Interval |
(2-Sided) 95% -5.30 to 1.36 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1739 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.62 | |
| Confidence Interval |
(2-Sided) 95% -5.97 to 0.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Week 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9761 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.94 | |
| Confidence Interval |
(2-Sided) 95% -5.93 to 4.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Week 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0998 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.18 | |
| Confidence Interval |
(2-Sided) 95% -6.78 to 0.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Week 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0239 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.97 | |
| Confidence Interval |
(2-Sided) 95% -7.54 to -0.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2018 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.98 | |
| Confidence Interval |
(2-Sided) 95% -9.25 to 1.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0011 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -5.67 | |
| Confidence Interval |
(2-Sided) 95% -9.48 to -1.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0026 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -5.27 | |
| Confidence Interval |
(2-Sided) 95% -9.06 to -1.48 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6336 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.47 | |
| Confidence Interval |
(2-Sided) 95% -7.84 to 2.90 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0950 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.49 | |
| Confidence Interval |
(2-Sided) 95% -7.38 to 0.41 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1451 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.18 | |
| Confidence Interval |
(2-Sided) 95% -7.06 to 0.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3434 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.28 | |
| Confidence Interval |
(2-Sided) 95% -8.43 to 1.87 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0016 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -5.45 | |
| Confidence Interval |
(2-Sided) 95% -9.23 to -1.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0006 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -5.88 | |
| Confidence Interval |
(2-Sided) 95% -9.65 to -2.10 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0025 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.64 | |
| Confidence Interval |
(2-Sided) 95% 1.31 to 7.96 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0129 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.98 | |
| Confidence Interval |
(2-Sided) 95% 0.64 to 7.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0206 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.04 | |
| Confidence Interval |
(2-Sided) 95% 0.46 to 7.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0841 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.26 | |
| Confidence Interval |
(2-Sided) 95% -0.30 to 6.82 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0088 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.67 | |
| Confidence Interval |
(2-Sided) 95% 0.91 to 8.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0034 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 5.07 | |
| Confidence Interval |
(2-Sided) 95% 1.34 to 8.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0138 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.55 | |
| Confidence Interval |
(2-Sided) 95% 0.71 to 8.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0073 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 4.85 | |
| Confidence Interval |
(2-Sided) 95% 1.02 to 8.69 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8284 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 1.29 | |
| Confidence Interval |
(2-Sided) 95% -2.46 to 5.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9525 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.86 | |
| Confidence Interval |
(2-Sided) 95% -2.88 to 4.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0856 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -3.22 | |
| Confidence Interval |
(2-Sided) 95% -6.91 to 0.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3374 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -2.08 | |
| Confidence Interval |
(2-Sided) 95% -6.36 to 2.20 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0534 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -4.24 | |
| Confidence Interval |
(2-Sided) 95% -8.53 to 0.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -10.8 | |
| Confidence Interval |
(2-Sided) 95% -15.33 to -6.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -9.22 | |
| Confidence Interval |
(2-Sided) 95% -13.63 to -4.81 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Meeting the SDAI-based Remission Criteria |
|---|---|
| Description | The SDAI was the numerical sum of five outcome parameter: SJC and TJC (based on a 28-joint assessment), PGA and MDG (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. The SDAI =< 3.3 indicates disease remission |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
0.00
0%
|
0.9
0.8%
|
0.00
0%
|
0.00
0%
|
0.00
0%
|
0.00
0%
|
0.00
0%
|
| Week 2 Day 14 |
0.00
0%
|
0.00
0%
|
0.00
0%
|
0.00
0%
|
1.8
1.6%
|
0.00
0%
|
0.00
0%
|
| Week 4 Day 28 |
0.00
0%
|
0.9
0.8%
|
0.9
0.8%
|
0.00
0%
|
4.5
4.1%
|
2.1
4.3%
|
0.00
0%
|
| Week 8 Day 56 |
0.00
0%
|
2.8
2.6%
|
3.6
3.3%
|
0.00
0%
|
6.3
5.7%
|
0.00
0%
|
0.00
0%
|
| Week 12 Day 84 |
0.00
0%
|
4.6
4.2%
|
6.4
5.8%
|
0.9
0.8%
|
9.0
8.1%
|
6.3
12.9%
|
6.0
12.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.48 to 4.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.91 to 2.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.92 to 2.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -2.91 to 2.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5726 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.26 to 4.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5976 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.91 | |
| Confidence Interval |
(2-Sided) 95% -2.47 to 4.28 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -6.06 to 6.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1446 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.74 | |
| Confidence Interval |
(2-Sided) 95% -0.94 to 6.42 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1050 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.64 | |
| Confidence Interval |
(2-Sided) 95% -0.76 to 8.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8979 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | -0.40 | |
| Confidence Interval |
(2-Sided) 95% -6.51 to 5.71 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1270 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 3.65 | |
| Confidence Interval |
(2-Sided) 95% -1.04 to 8.35 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0501 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 5.45 | |
| Confidence Interval |
(2-Sided) 95% -0.00 to 10.91 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 1, Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.31 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 2, Day 14 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.31 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 4, Day 28 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6564 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 2.05 | |
| Confidence Interval |
(2-Sided) 95% -7.00 to 11.11 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 8, Day 56 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -8.31 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo |
|---|---|---|
| Comments | Week 12, Day 84 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9051 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted Difference |
| Estimated Value | 0.68 | |
| Confidence Interval |
(2-Sided) 95% -10.58 to 11.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components |
|---|---|
| Description | The 36-Item Short Form Health Survey (SF-36v2) is a questionnaire used to assess functional health and well-being and consists of eight domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The SF-36v2 is summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. The PCS and MCS scores range from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement. |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Physical component score change: baseline-week 12 |
5.57
(5.98)
|
5.71
(6.85)
|
6.59
(7.54)
|
3.54
(6.81)
|
6.41
(6.43)
|
5.35
(7.48)
|
1.75
(6.39)
|
| Mental component score change: baseline-week 12 |
7.04
(9.32)
|
4.89
(10.57)
|
6.92
(12.06)
|
4.29
(10.51)
|
6.50
(10.79)
|
5.76
(10.22)
|
5.11
(10.10)
|
| Title | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score |
|---|---|
| Description | The FACIT-Fatigue Scale consists of 13 items designed to measure the degree of fatigue experienced by the patient in the previous 7 days. For each question, there are five possible responses: 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit), 4 (very much). A total fatigue score is calculated by summing all items, and possible total scores range from 0 (maximum fatigue) to 52 (no fatigue). A positive change from baseline indicates an improvement in the patient's fatigue (less fatigue). |
| Time Frame | Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Mean (Standard Deviation) [Score on a scale] |
9.00
(10.57)
|
8.21
(10.22)
|
8.95
(10.04)
|
7.08
(10.88)
|
9.59
(9.02)
|
8.85
(9.57)
|
5.71
(9.24)
|
| Title | Change From Baseline in Tender/Painful Joint Count (68 Joint Count) |
|---|---|
| Description | Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness. 68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-2.79
(7.25)
|
-4.12
(8.14)
|
-3.33
(9.27)
|
-3.81
(10.85)
|
-5.58
(9.41)
|
-6.57
(8.66)
|
-3.06
(11.01)
|
| Week 2 Day 19 |
-4.33
(12.31)
|
-6.36
(10.88)
|
-5.91
(9.38)
|
-5.78
(11.50)
|
-8.62
(10.46)
|
-6.08
(8.53)
|
-3.92
(10.77)
|
| Week 4 Day 28 |
-6.00
(8.89)
|
-7.90
(11.28)
|
-6.84
(9.53)
|
-7.55
(12.97)
|
-11.61
(11.43)
|
-7.79
(7.93)
|
-4.40
(12.37)
|
| Week 8 Day 56 |
-9.72
(8.20)
|
-11.57
(12.18)
|
-9.75
(10.93)
|
-10.75
(14.37)
|
-14.12
(11.33)
|
-11.65
(10.34)
|
-4.60
(12.41)
|
| Week 12 Day 84 |
-10.33
(9.40)
|
-12.72
(12.05)
|
-11.49
(11.15)
|
-10.55
(14.37)
|
-15.49
(12.31)
|
-13.73
(12.81)
|
-7.14
(13.32)
|
| Title | Change From Baseline in Swollen Joint Count (66 Joint Count) |
|---|---|
| Description | Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling. 66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-1.84
(5.19)
|
-2.89
(5.01)
|
-3.45
(6.02)
|
-3.35
(9.38)
|
-3.94
(5.33)
|
-3.45
(4.90)
|
-1.49
(4.49)
|
| Week 2 Day 14 |
-3.95
(6.44)
|
-4.78
(5.99)
|
-5.06
(5.14)
|
-4.23
(9.88)
|
-6.26
(5.98)
|
-3.29
(5.69)
|
-2.96
(6.27)
|
| Week 4 Day 28 |
-4.38
(4.55)
|
-6.33
(7.98)
|
-5.95
(6.09)
|
-5.47
(9.26)
|
-8.50
(6.39)
|
-4.21
(6.39)
|
-3.46
(5.62)
|
| Week 8 Day 56 |
-6.54
(5.78)
|
-8.06
(8.13)
|
-7.72
(7.44)
|
-7.41
(10.82)
|
-9.60
(6.94)
|
-6.81
(6.16)
|
-3.02
(7.76)
|
| Week 12 Day 84 |
-7.36
(5.88)
|
-8.89
(8.23)
|
-8.48
(7.01)
|
-8.26
(11.48)
|
-9.94
(6.91)
|
-7.65
(6.75)
|
-4.86
(5.84)
|
| Title | Change From Baseline in Patient Assessment Score of Arthritis Pain |
|---|---|
| Description | Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-9.00
(18.66)
|
-9.20
(20.56)
|
-11.18
(21.64)
|
-4.12
(22.43)
|
-15.75
(18.71)
|
-11.94
(21.25)
|
-2.76
(18.24)
|
| Week 2 Day 14 |
-6.08
(21.64)
|
-12.16
(20.09)
|
-17.08
(23.46)
|
-8.22
(25.72)
|
-18.13
(17.71)
|
-15.08
(21.87)
|
-4.72
(17.64)
|
| Week 4 Day 28 |
-13.41
(16.79)
|
-15.75
(21.97)
|
-18.63
(24.87)
|
-10.08
(27.16)
|
-20.21
(21.97)
|
-16.64
(27.86)
|
-7.54
(23.80)
|
| Week 8 Day 56 |
-18.38
(19.35)
|
-23.21
(22.10)
|
-25.95
(27.50)
|
-16.37
(27.65)
|
-24.70
(22.23)
|
-21.21
(27.13)
|
-7.13
(25.73)
|
| Week 12 Day 84 |
-23.14
(21.14)
|
-26.48
(23.30)
|
-30.63
(28.49)
|
-17.88
(29.42)
|
-26.30
(23.87)
|
-26.49
(27.65)
|
-13.98
(25.32)
|
| Title | Change From Baseline in Patient Global Assessment Score of Arthritis Pain |
|---|---|
| Description | Participant-assessed arthritis pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of arthritis pain (0 mm=none; 100 mm=very severe). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change indicated a decrease in participant-assessed arthritis pain. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-9.00
(15.88)
|
-10.30
(20.82)
|
-11.82
(22.52)
|
-3.07
(20.83)
|
-18.33
(20.81)
|
-13.15
(22.17)
|
-4.96
(19.18)
|
| Week 2 Day 14 |
-5.50
(20.98)
|
-13.70
(19.63)
|
-14.84
(24.08)
|
-5.39
(26.13)
|
-18.94
(22.33)
|
-15.46
(21.67)
|
-8.64
(19.43)
|
| Week 4 Day 28 |
-12.11
(16.68)
|
16.10
(23.48)
|
-17.75
(22.73)
|
-6.36
(25.99)
|
-21.78
(25.53)
|
-18.26
(27.53)
|
-10.96
(21.54)
|
| Week 8 Day 56 |
-19.19
(16.88)
|
-24.06
(24.99)
|
-22.59
(26.81)
|
-14.19
(29.80)
|
-26.77
(25.69)
|
-21.17
(25.98)
|
-11.82
(21.66)
|
| Week 12 Day 84 |
-23.33
(22.03)
|
-26.67
(26.89)
|
-27.33
(27.33)
|
-16.87
(28.68)
|
-26.24
(27.02)
|
-25.55
(27.52)
|
-13.80
(22.17)
|
| Title | Change From Baseline in Physician's Global Assessment Score of Arthritis |
|---|---|
| Description | Physician's assessment of participant's disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's assessment of the participant's disease activity (0 mm=very good; 100 mm=very poor). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change from baseline indicated an improvement in physician-assessed disease activity. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-7.89
(13.16)
|
-10.68
(15.41)
|
-12.82
(17.03)
|
-5.85
(15.44)
|
-14.23
(16.13)
|
-9.57
(17.10)
|
-7.66
(18.33)
|
| Week 2 Day 14 |
-11.10
(15.65)
|
-15.86
(16.77)
|
-18.30
(19.04)
|
-9.01
(18.07)
|
-21.33
(19.61)
|
-14.23
(18.50)
|
-9.85
(17.55)
|
| Week 4 Day 28 |
-16.89
(19.06)
|
-22.02
(18.61)
|
-20.92
(17.71)
|
-14.01
(21.03)
|
-28.81
(19.34)
|
-17.70
(20.49)
|
-12.73
(20.42)
|
| Week 8 Day 56 |
-24.59
(15.06)
|
-28.52
(21.11)
|
-29.67
(20.01)
|
-20.87
(23.85)
|
-36.16
(21.82)
|
-22.40
(20.43)
|
-9.91
(19.67)
|
| Week 12 Day 84 |
-26.81
(16.20)
|
-32.43
(19.24)
|
-34.48
(19.49)
|
-23.19
(23.39)
|
-37.18
(21.02)
|
-30.82
(21.95)
|
-18.44
(21.86)
|
| Title | Change From Baseline in C-Reactive Protein (CRP) Levels |
|---|---|
| Description | C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL) |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
0.14
(2.09)
|
0.30
(2.58)
|
0.22
(2.49)
|
0.01
(1.29)
|
-1.21
(2.37)
|
-0.12
(2.60)
|
-0.10
(1.76)
|
| Week 2 Day 14 |
0.27
(1.78)
|
-0.10
(1.92)
|
-0.21
(2.29)
|
-0.12
(1.53)
|
-0.93
(2.70)
|
-0.20
(2.38)
|
-0.25
(2.60)
|
| Week 4 Day 28 |
0.15
(2.45)
|
-0.25
(2.55)
|
-0.44
(2.30)
|
0.14
(2.00)
|
-1.11
(2.17)
|
-0.30
(2.58)
|
-0.24
(2.80)
|
| Week 8 Day 56 |
-0.49
(1.66)
|
-0.52
(1.83)
|
-0.89
(3.16)
|
-0.39
(1.64)
|
-1.14
(2.39)
|
-1.19
(2.18)
|
-0.26
(2.55)
|
| Week 12 Day 84 |
-0.59
(1.43)
|
-0.77
(1.89)
|
-1.30
(2.88)
|
-0.45
(1.71)
|
-1.03
(2.01)
|
-1.55
(2.35)
|
-0.56
(2.75)
|
| Title | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score |
|---|---|
| Description | The Stanford Health Assessment Questionnaire disability index is a patient-reported outcome used to assess difficulty in performing activities of daily living. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. To respond to each question, a four-level response with higher scores showing larger functional limitations, was chosen. Scoring is as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. The composite HAQ-DI score is the mean of the eight domain scores and the score ranges from 0 (no functional impairment) to 3 (maximum functional impairment). A negative change from baseline indicates improvement. |
| Time Frame | Days 7, 14, 28, 56, and 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 40 | 109 | 110 | 110 | 111 | 48 | 50 |
| Week 1 Day 7 |
-0.20
(0.37)
|
-0.15
(0.35)
|
-0.22
(0.48)
|
-0.10
(0.38)
|
-0.26
(0.42)
|
-0.19
(0.36)
|
-0.14
(0.46)
|
| Week 2 Day 14 |
-0.24
(0.39)
|
-0.23
(0.46)
|
-0.28
(0.50)
|
-0.17
(0.45)
|
-0.35
(0.47)
|
-0.23
(0.45)
|
-0.13
(0.49)
|
| Week 4 Day 28 |
-0.34
(0.47)
|
-0.32
(0.48)
|
-0.40
(0.50)
|
-0.19
(0.56)
|
-0.50
(0.50)
|
-0.23
(0.42)
|
-0.17
(0.44)
|
| Week 8 Day 56 |
-0.49
(0.47)
|
-0.44
(0.56)
|
-0.56
(0.55)
|
-0.40
(0.64)
|
-0.60
(0.55)
|
-0.45
(0.50)
|
-0.23
(0.55)
|
| Week 12 Day 84 |
-0.51
(0.57)
|
-0.57
(0.57)
|
-0.65
(0.60)
|
-0.35
(0.68)
|
-0.65
(0.61)
|
-0.53
(0.61)
|
-0.30
(0.62)
|
| Title | Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss) |
|---|---|
| Description | The Pharmacokinetics (PK) evaluation may include, but will not be limited to, plasma GDC-0853 concentrations and population PK model estimated PK exposures (area under the plasma concentration-time curve [AUC]. AUC was measured in Nanograms(ng) per millilitre(mL)*hour (hr) |
| Time Frame | Pre-dose (0 hours) up to 10 hours post-dose on Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. Data were presented only for arms in which GDC-0853 was administered. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 2: GDC-0853 High Dose |
|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 39 | 106 | 108 | 48 |
| Mean (Standard Deviation) [Ng/mL*(hr)] |
1170
(1600)
|
2910
(3180)
|
9380
(4860)
|
9890
(5480)
|
| Title | Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss) |
|---|---|
| Description | Cmax is the maximum (peak) plasma concentration over the dosing interval at steady state (ss) |
| Time Frame | Pre-dose (0 hours) up to 10 hours post-dose on Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. Data were presented only for arms in which GDC-0853 was administered. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 2: GDC-0853 High Dose |
|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 39 | 106 | 108 | 48 |
| Mean (Standard Deviation) [Nanogram per Milliliter (ng/mL)] |
110
(116)
|
280
(223)
|
591
(282)
|
621
(302)
|
| Title | Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss) |
|---|---|
| Description | Cmin is the minimum concentration over the dosing interval at steady state (ss) |
| Time Frame | Pre-dose (0 hours) up to 10 hours post-dose on Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point. Data were presented only for arms in which GDC-0853 was administered. |
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 2: GDC-0853 High Dose |
|---|---|---|---|---|
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. |
| Measure Participants | 39 | 106 | 108 | 48 |
| Mean (Standard Deviation) [Nanogram per Milliliter (ng/mL)] |
22.4
(41.0)
|
54.7
(83.4)
|
250
(146)
|
263
(170)
|
Adverse Events
| Time Frame | From randomization to end of study (approximately 22 months) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||
| Arm/Group Title | Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo | |||||||
| Arm/Group Description | Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigators discretion. | |||||||
All Cause Mortality |
||||||||||||||
| Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 0/109 (0%) | 1/110 (0.9%) | 0/110 (0%) | 0/111 (0%) | 0/49 (0%) | 0/49 (0%) | |||||||
Serious Adverse Events |
||||||||||||||
| Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/40 (0%) | 1/109 (0.9%) | 3/110 (2.7%) | 1/110 (0.9%) | 2/111 (1.8%) | 0/49 (0%) | 0/49 (0%) | |||||||
| Cardiac disorders | ||||||||||||||
| MYOCARDIAL INFARCTION | 0/40 (0%) | 0 | 0/109 (0%) | 0 | 1/110 (0.9%) | 1 | 0/110 (0%) | 0 | 0/111 (0%) | 0 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||
| SMALL INTESTINAL DISORDERS | 0/40 (0%) | 0 | 0/109 (0%) | 0 | 0/110 (0%) | 0 | 0/110 (0%) | 0 | 1/111 (0.9%) | 1 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| Infections and infestations | ||||||||||||||
| CELLULITS | 0/40 (0%) | 0 | 0/109 (0%) | 0 | 1/110 (0.9%) | 1 | 0/110 (0%) | 0 | 0/111 (0%) | 0 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| PNEUMONIA | 0/40 (0%) | 0 | 1/109 (0.9%) | 1 | 0/110 (0%) | 0 | 1/110 (0.9%) | 1 | 0/111 (0%) | 0 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| PYELONEPHRITIS OBSTRUCTION | 0/40 (0%) | 0 | 0/109 (0%) | 0 | 1/110 (0.9%) | 1 | 0/110 (0%) | 0 | 0/111 (0%) | 0 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| Nervous system disorders | ||||||||||||||
| SEIZURE | 0/40 (0%) | 0 | 0/109 (0%) | 0 | 0/110 (0%) | 0 | 0/110 (0%) | 0 | 1/111 (0.9%) | 1 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 0/40 (0%) | 0 | 0/109 (0%) | 0 | 0/110 (0%) | 0 | 1/110 (0.9%) | 1 | 0/111 (0%) | 0 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| PLEURAL EFFUSION | 0/40 (0%) | 0 | 0/109 (0%) | 0 | 0/110 (0%) | 0 | 1/110 (0.9%) | 1 | 0/111 (0%) | 0 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo | Cohort 1: GDC-0853 High Dose + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab Placebo | Cohort 1: GDC-0853 Placebo + Adalimumab | Cohort 2: GDC-0853 High Dose | Cohort 2: GDC-0853 Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/40 (22.5%) | 18/109 (16.5%) | 11/110 (10%) | 15/110 (13.6%) | 16/111 (14.4%) | 3/49 (6.1%) | 7/49 (14.3%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| NAUSEA | 2/40 (5%) | 2 | 5/109 (4.6%) | 5 | 3/110 (2.7%) | 3 | 5/110 (4.5%) | 6 | 1/111 (0.9%) | 1 | 3/49 (6.1%) | 4 | 1/49 (2%) | 1 |
| VOMITING | 2/40 (5%) | 2 | 1/109 (0.9%) | 1 | 0/110 (0%) | 0 | 0/110 (0%) | 0 | 1/111 (0.9%) | 1 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| Infections and infestations | ||||||||||||||
| UPPER RESPIRATORY TRACT INFECTION | 1/40 (2.5%) | 1 | 3/109 (2.8%) | 3 | 3/110 (2.7%) | 3 | 2/110 (1.8%) | 2 | 6/111 (5.4%) | 6 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| URINARY TRACT INFECTION | 2/40 (5%) | 3 | 2/109 (1.8%) | 3 | 0/110 (0%) | 0 | 2/110 (1.8%) | 2 | 8/111 (7.2%) | 10 | 0/49 (0%) | 0 | 3/49 (6.1%) | 3 |
| Investigations | ||||||||||||||
| ALANINE AMINOTRANFERASE INCREASED | 2/40 (5%) | 3 | 5/109 (4.6%) | 5 | 4/110 (3.6%) | 4 | 1/110 (0.9%) | 1 | 1/111 (0.9%) | 1 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 2/40 (5%) | 2 | 4/109 (3.7%) | 4 | 3/110 (2.7%) | 4 | 1/110 (0.9%) | 1 | 1/111 (0.9%) | 1 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| Nervous system disorders | ||||||||||||||
| HEADACHE | 2/40 (5%) | 2 | 4/109 (3.7%) | 5 | 5/110 (4.5%) | 5 | 5/110 (4.5%) | 5 | 0/111 (0%) | 0 | 0/49 (0%) | 0 | 0/49 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||
| ANXIETY | 0/40 (0%) | 0 | 0/109 (0%) | 0 | 0/110 (0%) | 0 | 0/110 (0%) | 0 | 0/111 (0%) | 0 | 0/49 (0%) | 0 | 3/49 (6.1%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-La Roche |
| Phone | 800 821-8590 |
| genentech@druginfo.com |
Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT02833350
Other Study ID Numbers:
- GA29350
- 2016-000335-40
First Posted:
Jul 14, 2016
Last Update Posted:
Jun 12, 2020
Last Verified:
Jun 1, 2020