A Study to Evaluate the Long-Term Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Rheumatoid Arthritis Enrolled in Study GA29350
Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02983227
Collaborator
(none)
496
104
2
31.5
4.8
0.2
Study Details
Study Description
Brief Summary
A study to evaluate the long-term safety and efficacy of GDC-0853 in participants with moderate to severe active Rheumatoid Arthritis (RA) who have completed 12 weeks of study treatment in Study GA29350. Eligible participants from Study GA29350 who elect to participate will receive treatment with GDC-0853 twice daily (BID) in an open-label fashion for 52 weeks, followed by a safety follow-up period of 8 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
496 participants
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Open-Label Extension Study of Patients Previously Enrolled in Study GA29350 to Evaluate the Long-Term Safety and Efficacy of GDC-0853 in Patients With Moderate to Severe Rheumatoid Arthritis
Actual Study Start Date
:
Nov 30, 2016
Actual Primary Completion Date
:
Jul 17, 2019
Actual Study Completion Date
:
Jul 17, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GDC-0853 (200mg BID) Cohort 1 Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. |
Drug: GDC-0853
GDC-0853 was administered orally at a dose of 200mg, as per the dosing schedules described above.
Other Names:
|
| Experimental: GDC-0853 (200mg BID) Cohort 2 Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
Drug: GDC-0853
GDC-0853 was administered orally at a dose of 200mg, as per the dosing schedules described above.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Adverse Events (AEs) [Day 1 up until 8 weeks after the last dose of study drug (up to 1 year, 2 months)]
An Adverse Event (AE) 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.
- Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 52 [Week 52]
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].
Secondary Outcome Measures
- Percentage of Participants Achieving ACR50 Response up to Week 12 [Weeks 4, 8 and 12]
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 [Weeks 4, 8, 12, 24, 36 and 52]
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 70% (ACR70) Response [Weeks 4, 8, 12, 24, 36 and 52]
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].
- Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP) [Baseline, Weeks 4, 8, 12, 24, 36 and 52]
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.
- Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP) [Baseline, Weeks 4, 8, 12, 24, 36 and 52]
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.
- Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR) [Baseline, Weeks 4, 8, 12, 24, 36 and 52]
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.
- Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR) [Baseline, Weeks 4, 8, 12, 24, 36 and 52]
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 Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) [Weeks 4, 8, 12, 24, 36 and 52]
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.
- Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 [Weeks 4, 8, 12, 24, 36 and 52]
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 ACR/EULAR Remission [Weeks 4, 8, 12, 24, 36 and 52]
Assessed according to the Boolean based definition (tender joint count =<1, swollen joint count =<1, C-reactive Protein (CRP) =<1, and patient global assessment =<1)
- Change From Baseline in Simplified Disease Activity Index (SDAI) [Weeks 4, 8, 12, 24, 36 and 52]
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
- Change From Baseline in Clinical Disease Activity Index (CDAI) [Weeks 4, 8, 12, 24, 36 and 52]
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.
- Change From Baseline in Tender/Painful Joint Count Based on 68 Joints [Weeks 4, 8, 12, 24, 36 and 52]
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 Based on 66 Joints [Weeks 4, 8, 12, 24, 36 and 52]
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's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score [Weeks 4, 8, 12, 24, 36 and 52]
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's Global Assessment of Arthritis, Using VAS Score [Weeks 4, 8, 12, 24, 36 and 52]
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 of Arthritis, Using VAS Score [Weeks 4, 8, 12, 24, 36 and 52]
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 [Weeks 4, 8, 12, 24, 36 and 52]
C-reactive protein is a biological marker of inflammation and is measured in milligrams per decilitre (mg/dL)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score [Weeks 4, 8, 12, 24, 36 and 52]
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.
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components [Weeks 12, 24 and 52]
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 [Weeks 12, 24 and 52]
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).
- Area Under the Concentration Time Curve (AUC) of GDC-0853 at Steady State (AUC,ss) [Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination]
Population PK model estimated AUC of GDC-0853 at steady-state. AUC was measured in Nanograms (ng) per millilitre(mL)*hour (hr).
- Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss) [Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination]
Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss).
- Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss) [Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination]
Population PK model estimated plasma decay half life of GDC-0853 at steady-state.
- Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss) [Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination]
Population PK model estimated apparent oral clearance of GDC-0853 at steady-state.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 76 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Completion of treatment as specified in Study GA29350, including completion of the Day 84 study visit assessments
-
Acceptable safety and tolerability during Study GA29350 as determined by the investigator or Medical Monitor
-
Have not received any prohibited medications in Study GA29350
-
While taking methotrexate, must be willing to receive oral folic acid (at least 5 milligrams per week [mg/week])
-
If receiving oral corticosteroids (less than or equal to [</=] 10 milligrams per day [mg/day] prednisone or equivalent) and/or non-steroidal anti-inflammatory drugs, doses have remained stable for the duration of Study GA29350
Exclusion Criteria:
-
Met protocol defined treatment stopping criteria during Study GA29350
-
Treatment with any investigational agent (i.e., other than study drug) or live/attenuated vaccine or any other prohibited medication during Study GA29350 or since the last administration of study drug in Study GA29350
-
In the opinion of the investigator, any new (since initially enrolling in the Phase II Study GA29350), significant, uncontrolled comorbidity that would increase the risk to the participant in Study GA30067
-
Pregnant or lactating, or intending to become pregnant during the study
-
Participants who experienced a de novo or reactivated serious viral infection such as hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) during the Phase II Study GA29350
-
Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics during the Phase II Study GA29350
-
Participants who developed a malignancy during the Phase II Study GA29350
-
12-lead electrocardiogram (ECG) on Day 84 in Study GA29350 that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
-
Current treatment with medications that are well known to prolong the QT interval
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arizona Arthritis & Rheumatology Associates, P.C. | Glendale | Arizona | United States | 85306 |
| 2 | Medvin Clinical Research | Covina | California | United States | 91723 |
| 3 | TriWest Research Associates, LLC | El Cajon | California | United States | 92020 |
| 4 | Saint Jude Heritage Medical Grp | Fullerton | California | United States | 92835 |
| 5 | RASF-Clinical Research Center | Boca Raton | Florida | United States | 33486 |
| 6 | Clinical Research of West Florida | Clearwater | Florida | United States | 33765 |
| 7 | Medication Management | Greensboro | North Carolina | United States | 27408 |
| 8 | Oregon Health & Science Uni | Portland | Oregon | United States | 97239 |
| 9 | Metroplex Clinical Research Centre | Dallas | Texas | United States | 75231 |
| 10 | Baylor Research Inst. | Dallas | Texas | United States | 75246 |
| 11 | Accurate Clinical Research | Houston | Texas | United States | 77089 |
| 12 | Instituto de Investigaciones Clinicas-Mar del Plata | Buenos Aires | Argentina | B7600FZN | |
| 13 | APRILLUS | Buenos Aires | Argentina | C1194AAO | |
| 14 | Instituto centenario | Buenos Aires | Argentina | C1204AAD | |
| 15 | Centro de Investigacion en Enfermedades Reumaticas CIER | Ciudad Autonoma Buenos Aires | Argentina | C1055AAF | |
| 16 | Expertia S.A- Mautalen Salud e Investigación | Ciudad Autonoma Buenos Aires | Argentina | C1128AAE | |
| 17 | CCBR - Buenos Aires - AR; AxisMed SRL | Ciudad Autonoma Buenos Aires | Argentina | C1430CKE | |
| 18 | ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas | Cordoba | Argentina | X5000BNB | |
| 19 | Centro de Investigaciones Medicas Mar Del Plata | Mar del Plata | Argentina | B7600DHK | |
| 20 | Instituto de Investigaciones Clinicas | Rosario | Argentina | S2000CVD | |
| 21 | CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica | San Juan | Argentina | 5400 | |
| 22 | Centro Medico Privado de Reumatologia; Reumathology | San Miguel | Argentina | T4000AXL | |
| 23 | CIP - Centro Internacional de Pesquisa X; Pesquisa Clinica | Goiânia | GO | Brazil | 74110-120 |
| 24 | CMiP - Centro Mineiro de Pesquisa*X* | Juiz de Fora | MG | Brazil | 36010-570 |
| 25 | Centro de Estudos em Terapias Inovadoras - CETI | Curtiba | PR | Brazil | 80030-110 |
| 26 | CCBR Brasil Centro de Pesquisas e Análises Clínicas Ltda. | Rio de Janeiro | RJ | Brazil | 21941-913 |
| 27 | LMK Serviços Médicos S/S | Porto Alegre | RS | Brazil | 90480-000 |
| 28 | CAEP - Centro Avancado de Estudos e Pesquisas Ltda. | Campinas | SP | Brazil | 13087-567 |
| 29 | IMA Brasil - Instituto de Medicina Avancada | Sao Paulo | SP | Brazil | 05437-000 |
| 30 | MHAT "Eurohospital" - Plovdiv, OOD; Internal Department | Plovdiv | Bulgaria | 4002 | |
| 31 | UMHAT "Kaspela", EOOD | Plovdiv | Bulgaria | 4002 | |
| 32 | Medizinski Zentrar-1-Sevlievo EOOD | Sevlievo | Bulgaria | 5400 | |
| 33 | MHAT "Hadzhi Dimitar", OOD | Sliven | Bulgaria | 8800 | |
| 34 | Medical Center Excelsior OOD | Sofia | Bulgaria | 1000 | |
| 35 | NMTH "Tsar Boris III" | Sofia | Bulgaria | 1233 | |
| 36 | DCC "Alexandrovska", EOOD; Clinic of Neurology | Sofia | Bulgaria | 1431 | |
| 37 | MC "Synexus - Sofia", EOOD | Sofia | Bulgaria | 1784 | |
| 38 | UMHAT "SofiaMed", OOD; Department of Neurology | Sofia | Bulgaria | 1797 | |
| 39 | Centro de Investigacion Medico Asistencial S.A.S | Barranquilla | Colombia | 80020 | |
| 40 | Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM | Bogota | Colombia | 110221 | |
| 41 | Riesgo de Fractura S.A. | Bogota | Colombia | 110221 | |
| 42 | Consultorio Medico en Fundacion el Hospitalito de morelos A.C. | Cuernavaca | Morelos | Mexico | 62170 |
| 43 | Centro de Investigacion en Reumatologia | Merida | Yucatan | Mexico | 97070 |
| 44 | Consultorio Particular del Dr. Miguel Cortes Hernandez | Cuernavaca | Mexico | 62290 | |
| 45 | Centro de Investigacion de Tratam Innovadores de Sin SC | Culiacan | Mexico | 80230 | |
| 46 | Centro de Investigacion en Enfermedades Reumaticas y Osteoporosis | Mexicali | Mexico | 21100 | |
| 47 | Centro de Investigacion Clínica GRAMEL S.C | Mexico | Mexico | 03720 | |
| 48 | Policlinica Medica de Queretaro S.C. | Queretaro | Mexico | 76000 | |
| 49 | Clinical Research Institute | Tlalnepantla | Mexico | 54055 | |
| 50 | Unidad de Enfermedades Reumaticas y Cronicodegenerativas | Torreon | Mexico | 27000 | |
| 51 | NZOZ ZDROWIE Osteo-Medic | Bialystok | Poland | 15-351 | |
| 52 | Szpital Uniwersytecki; nr 2 im. Dr J. Biziela | Bydgoszcz | Poland | 85-168 | |
| 53 | Centrum Medyczne Pratia Katowice I | Katowice | Poland | 40-081 | |
| 54 | CCBR - Lodz - PL | Lodz | Poland | 90-368 | |
| 55 | ETYKA Osrodek Badan Kliniczynch | Olsztyn | Poland | 10-117 | |
| 56 | Ai Centrum Medyczne Sp. Z O.O Sp.K. | Poznan | Poland | 61-113 | |
| 57 | Medycyna Kliniczna | Warszawa | Poland | 00-660 | |
| 58 | Centrum Medyczne AMED | Warszawa | Poland | 03-291 | |
| 59 | KO-MED Centra Kliniczne Zamosc | Zamosc | Poland | 22400 | |
| 60 | SBIH of Yaroslavl region " Regional Clinical Hospital "; Therapy | Yaroslavl | Jaroslavl | Russian Federation | 150062 |
| 61 | Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova | Moscow | Moskovskaja Oblast | Russian Federation | 115522 |
| 62 | SBIH of Moscow "City Clinical Hospital # 1 n. a. N. I. Pirogov" | Moscow | Moskovskaja Oblast | Russian Federation | 119049 |
| 63 | SPb SBIH "Clinical Rheumatological Hospital # 25" | Saint-Petersburg | Sankt Petersburg | Russian Federation | 190068 |
| 64 | Sanavita LLC | Sankt-peterburg | Sankt Petersburg | Russian Federation | 195257 |
| 65 | LLC Medical Sanitary Unit | Sankt-peterburg | Sankt Petersburg | Russian Federation | 196066 |
| 66 | Center of Family Medicine LC | Yekaterinburg | Sankt Petersburg | Russian Federation | 620043 |
| 67 | SBHI of Yaroslavl Region Clinical Hospital #3 | Yaroslavl | Volgograd | Russian Federation | 150051 |
| 68 | SMMIH "Chelyabinsk Regional Clinical Hospital" | Chelyabinsk | Voronez | Russian Federation | 454076 |
| 69 | SAHI of Kem. "Regional Clinical Hospital for War Veterans" | Kemerovo | Russian Federation | 650000 | |
| 70 | OOO Family Polyclinic | Korolev, Moscow Region | Russian Federation | 141060 | |
| 71 | Practical Medicine | Moscow | Russian Federation | 115404 | |
| 72 | Limited Liability Company "Centre of Medical Common Practice" | Novosibirsk | Russian Federation | 630091 | |
| 73 | Ultramed | Omsk | Russian Federation | 644024 | |
| 74 | SEIHPE Saratov State Medical University n.a. V.I. Razumovskiy | Saratov | Russian Federation | 410012 | |
| 75 | NIH "Departmental Hospital on Station Smolensk of OJSC "Russian Railways" | Smolensk | Russian Federation | 214025 | |
| 76 | Siberian State Medical University | Tomsk | Russian Federation | 634050 | |
| 77 | SHI Ulyanovsk Reg Clinical Hospital | Ulyanovsk | Russian Federation | 432063 | |
| 78 | Territorial Clinical Hospital #2 | Vladivostok | Russian Federation | 690035 | |
| 79 | Institute of Rheumatology | Belgrade | Serbia | 11000 | |
| 80 | Clinical Center Kragujevac | Kragujevac | Serbia | 34000 | |
| 81 | Institute of Treatment and Rehabilitation "Niska Banja" | Niska Banja | Serbia | 18205 | |
| 82 | Special hospital for rheumatic diseases Novi Sad | Novi Sad | Serbia | 21000 | |
| 83 | General Hospital "Dr Laza K. Lazarevic" Sabac | Sabac | Serbia | 15000 | |
| 84 | MI of Healthcare Kyiv RCH P.L. Shupyk NMA of PGE | Kyiv | Chernihiv Governorate | Ukraine | 01601 |
| 85 | CI of Healthcare Kharkiv CCH #8 Dept of Therapy Kharkiv MA of PGE of MOHU | Kharkiv | Kharkiv Governorate | Ukraine | 61176 |
| 86 | CI of TRC | Ternopil | Kherson Governorate | Ukraine | 46002 |
| 87 | Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU | Ivano-Frankivsk | KIEV Governorate | Ukraine | 76008 |
| 88 | SI NSС M.D. Strazhesko Institute of Cardiology of NAMSU | Kyiv | KIEV Governorate | Ukraine | 03680 |
| 89 | Medical Center of Revmotsentr LLC | Kyiv | KIEV Governorate | Ukraine | 04070 |
| 90 | Medical Center of Limited Liability Company Medical Clinic Blagomed | Kyiv | KIEV Governorate | Ukraine | 1023 |
| 91 | Med Center of International Institute of Clinical Trials LLC; Medical Center "OK!Clinic+" | Kyiv | KIEV Governorate | Ukraine | 2091 |
| 92 | Lviv Regional Clinical Hospital Dept of Rehmuaatology D. Halytskyi Lviv NMU | Lviv | KIEV Governorate | Ukraine | 79010 |
| 93 | CH of State Border Service of Ukraine (Military Base 2522); Dept of Therapy, D.Halytskyi Lviv NMU | Lviv | KIEV Governorate | Ukraine | 79014 |
| 94 | A.Novak Transcarpathian Regional Clinical Hospital | Uzhgorod | KIEV Governorate | Ukraine | 88018 |
| 95 | National Pirogov Memorial Medical University | Vinnytsia | Podolia Governorate | Ukraine | 21018 |
| 96 | Railway Transp DCH of HealthCenter Branch of PJSC Ukr Railway Dept of Rheumatology | Dnipro | Tavria Okruha | Ukraine | 49008 |
| 97 | City Clinical Hospital #9 Dept of Therapy SI Zaporizhzhia MA of PGE of MoHU | Zaporizhzhia | Tavria Okruha | Ukraine | 69065 |
| 98 | CI City Hospital #1 | Zaporizhzhia | Tavria Okruha | Ukraine | 69104 |
| 99 | CI Lutsk CCH Volyn Regional Center of Cardiovascular Pathology and Thrombolysis | Lutsk | Volhynian Governorate | Ukraine | 43024 |
| 100 | GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine | Kharkiv | Ukraine | 61039 | |
| 101 | CNI Consultative and Diagnostic Center of Desnianskyi District of Kyiv | Kyiv | Ukraine | 02232 | |
| 102 | M.V. Sklifosovsky Poltava RCH Dept of Rheumatology HSEIU UMSA | Poltava | Ukraine | 36011 | |
| 103 | CI City Hospital #7 | Zaporizhzhia | Ukraine | 69118 | |
| 104 | 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:
NCT02983227
Other Study ID Numbers:
- GA30067
- 2016-000498-19
First Posted:
Dec 6, 2016
Last Update Posted:
Aug 3, 2020
Last Verified:
Jul 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted at 138 centers in 19 countries. |
|---|---|
| Pre-assignment Detail | 496 participants were enrolled into this OLE study and were included in the ITT and Safety populations. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Period Title: Overall Study | ||
| STARTED | 410 | 86 |
| COMPLETED | 351 | 72 |
| NOT COMPLETED | 59 | 14 |
Baseline Characteristics
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 | Total |
|---|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. | Total of all reporting groups |
| Overall Participants | 410 | 86 | 496 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
49.9
(11.7)
|
53.5
(12.5)
|
50.5
(11.9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
334
81.5%
|
64
74.4%
|
398
80.2%
|
| Male |
76
18.5%
|
22
25.6%
|
98
19.8%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Hispanic or Latino |
136
33.2%
|
30
34.9%
|
166
33.5%
|
| Not Hispanic or Latino |
267
65.1%
|
56
65.1%
|
323
65.1%
|
| Not Stated |
2
0.5%
|
0
0%
|
2
0.4%
|
| Unknown |
5
1.2%
|
0
0%
|
5
1%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| American Indian or Alaska native |
27
6.6%
|
11
12.8%
|
38
7.7%
|
| Asian |
1
0.2%
|
0
0%
|
1
0.2%
|
| Black or African American |
7
1.7%
|
2
2.3%
|
9
1.8%
|
| Multiple |
7
1.7%
|
2
2.3%
|
9
1.8%
|
| Unknown |
3
0.7%
|
0
0%
|
3
0.6%
|
| White |
365
89%
|
71
82.6%
|
436
87.9%
|
Outcome Measures
| Title | Percentage of Participants With Adverse Events (AEs) |
|---|---|
| Description | An Adverse Event (AE) 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. |
| Time Frame | Day 1 up until 8 weeks after the last dose of study drug (up to 1 year, 2 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety-Evaluable Population was defined as all participants who received any study drug and had at least one assessment of safety. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 410 | 86 |
| Number [Percentage] |
60.2
|
57.0
|
| Title | Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 52 |
|---|---|
| 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 | Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 410 | 86 |
| Number (95% Confidence Interval) [Percentage] |
57.1
|
50.0
|
| Title | Percentage of Participants Achieving ACR50 Response up to Week 12 |
|---|---|
| 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 | Weeks 4, 8 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 410 | 86 |
| Week 4 |
37.1
|
29.1
|
| Week 8 |
42.4
|
34.9
|
| Week 12 |
45.6
|
39.5
|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 410 | 86 |
| Week 4 |
69.0
|
58.1
|
| Week 8 |
72.9
|
68.6
|
| Week 12 |
74.4
|
73.3
|
| Week 24 |
75.4
|
72.1
|
| Week 36 |
75.1
|
72.1
|
| Week 52 |
75.4
|
68.6
|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 410 | 86 |
| Week 4 |
19.8
|
12.8
|
| Week 8 |
21.7
|
17.4
|
| Week 12 |
23.9
|
19.8
|
| Week 24 |
30.2
|
20.9
|
| Week 36 |
32.2
|
25.6
|
| Week 52 |
36.3
|
27.9
|
| Title | Disease Activity Score 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 | Baseline, Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 406 | 86 |
| Baseline |
5.49
(0.85)
|
5.59
(0.90)
|
| Week 4 |
3.64
(1.11)
|
4.09
(1.19)
|
| Week 8 |
3.48
(1.06)
|
3.81
(1.15)
|
| Week 12 |
3.37
(1.09)
|
3.73
(1.11)
|
| Week 24 |
3.16
(1.05)
|
3.55
(1.18)
|
| Week 36 |
3.05
(1.05)
|
3.36
(1.06)
|
| Week 52 |
2.90
(1.03)
|
3.17
(1.28)
|
| Title | Disease Activity Score 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 | Baseline, Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 391 | 86 |
| Baseline |
5.83
(0.88)
|
5.95
(0.94)
|
| Week 4 |
3.70
(1.19)
|
4.22
(1.34)
|
| Week 8 |
3.53
(1.13)
|
3.92
(1.25)
|
| Week 12 |
3.39
(1.14)
|
3.81
(1.21)
|
| Week 24 |
3.18
(1.13)
|
3.64
(1.27)
|
| Week 36 |
3.06
(1.14)
|
3.44
(1.21)
|
| Week 52 |
2.87
(1.09)
|
3.22
(1.40)
|
| Title | Disease Activity Score 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 | Baseline, Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 404 | 86 |
| Baseline |
6.17
(0.79)
|
6.38
(0.88)
|
| Week 4 |
4.25
(1.16)
|
4.80
(1.26)
|
| Week 8 |
4.04
(1.14)
|
4.51
(1.17)
|
| Week 12 |
3.89
(1.16)
|
4.40
(1.11)
|
| Week 24 |
3.65
(1.08)
|
4.15
(1.27)
|
| Week 36 |
3.46
(1.15)
|
3.96
(1.15)
|
| Week 52 |
3.35
(1.14)
|
3.74
(1.31)
|
| Title | Disease Activity Score 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 | Baseline, Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 390 | 86 |
| Baseline |
6.48
(0.85)
|
6.71
(0.96)
|
| Week 4 |
4.27
(1.25)
|
4.89
(1.41)
|
| Week 8 |
4.04
(1.23)
|
4.58
(1.29)
|
| Week 12 |
3.87
(1.23)
|
4.44
(1.25)
|
| Week 24 |
3.62
(1.16)
|
4.20
(1.37)
|
| Week 36 |
3.43
(1.24)
|
3.99
(1.30)
|
| Week 52 |
3.27
(1.20)
|
3.74
(1.42)
|
| Title | Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28) |
|---|---|
| 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. |
| Time Frame | Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 410 | 86 |
| Week 4 |
8.8
2.1%
|
7.0
8.1%
|
| Week 8 |
10.7
2.6%
|
8.1
9.4%
|
| Week 12 |
13.9
3.4%
|
8.1
9.4%
|
| Week 24 |
17.8
4.3%
|
14.0
16.3%
|
| Week 36 |
22.4
5.5%
|
11.6
13.5%
|
| Week 52 |
25.6
6.2%
|
23.3
27.1%
|
| Title | Percentage of Participants With Low Disease Activity (LDA) Based on DAS28 |
|---|---|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 410 | 86 |
| Week 4 |
20.0
4.9%
|
12.8
14.9%
|
| Week 8 |
21.2
5.2%
|
17.4
20.2%
|
| Week 12 |
26.6
6.5%
|
12.8
14.9%
|
| Week 24 |
33.7
8.2%
|
27.9
32.4%
|
| Week 36 |
38.3
9.3%
|
29.1
33.8%
|
| Week 52 |
42.2
10.3%
|
29.1
33.8%
|
| Title | Percentage of Participants With ACR/EULAR Remission |
|---|---|
| Description | Assessed according to the Boolean based definition (tender joint count =<1, swollen joint count =<1, C-reactive Protein (CRP) =<1, and patient global assessment =<1) |
| Time Frame | Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 401 | 86 |
| Week 4 |
5.0
1.2%
|
5.8
6.7%
|
| Week 8 |
7.8
1.9%
|
5.9
6.9%
|
| Week 12 |
7.4
1.8%
|
7.2
8.4%
|
| Week 24 |
13.0
3.2%
|
6.0
7%
|
| Week 36 |
15.6
3.8%
|
11.4
13.3%
|
| Week 52 |
17.8
4.3%
|
10.7
12.4%
|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 373 | 84 |
| Week 4 |
-24.36
(13.58)
|
-21.00
(13.49)
|
| Week 8 |
-26.17
(13.58)
|
-24.06
(13.57)
|
| Week 12 |
-27.91
(12.89)
|
-25.21
(13.37)
|
| Week 24 |
-29.61
(13.14)
|
-26.45
(14.17)
|
| Week 36 |
-30.47
(13.72)
|
-28.22
(14.16)
|
| Week 52 |
-31.69
(13.12)
|
-29.68
(13.77)
|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intent-To-Treat (ITT) Population was defined as all eligible participants enrolled in this OLE study. Number of participants for whom data were actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 374 | 86 |
| Week 4 |
-23.41
(13.11)
|
-19.81
(13.15)
|
| Week 8 |
-25.14
(13.06)
|
-22.48
(12.59)
|
| Week 12 |
-26.82
(12.31)
|
-23.82
(12.37)
|
| Week 24 |
-28.52
(12.52)
|
-25.09
(13.18)
|
| Week 36 |
-29.40
(12.99)
|
-26.66
(12.98)
|
| Week 52 |
-30.61
(12.43)
|
-27.43
(13.43)
|
| Title | Change From Baseline in Tender/Painful Joint Count Based on 68 Joints |
|---|---|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 406 | 86 |
| Week 4 |
-15.02
(12.38)
|
-13.23
(12.27)
|
| Week 8 |
-16.11
(12.45)
|
-15.19
(12.59)
|
| Week 12 |
-16.55
(12.39)
|
-15.99
(12.03)
|
| Week 24 |
-17.96
(12.24)
|
-16.65
(11.35)
|
| Week 36 |
-18.48
(12.77)
|
-17.51
(11.60)
|
| Week 52 |
-18.70
(12.99)
|
-17.73
(11.88)
|
| Title | Change From Baseline in Swollen Joint Count Based on 66 Joints |
|---|---|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 406 | 86 |
| Week 4 |
-10.20
(8.43)
|
-7.85
(6.71)
|
| Week 8 |
-10.95
(8.48)
|
-9.12
(6.65)
|
| Week 12 |
-11.40
(8.22)
|
-9.08
(6.84)
|
| Week 24 |
-11.93
(8.33)
|
-9.86
(6.61)
|
| Week 36 |
-12.15
(8.57)
|
-9.98
(6.96)
|
| Week 52 |
-12.17
(8.55)
|
-9.59
(8.78)
|
| Title | Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score |
|---|---|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 371 | 86 |
| Week 4 |
-30.62
(26.60)
|
-26.34
(25.98)
|
| Week 8 |
-32.57
(26.77)
|
-27.21
(23.36)
|
| Week 12 |
-35.68
(26.44)
|
-29.49
(26.70)
|
| Week 24 |
-37.19
(26.85)
|
-30.30
(26.42)
|
| Week 36 |
-39.50
(27.20)
|
-33.14
(27.22)
|
| Week 52 |
-42.40
(26.22)
|
-38.21
(26.37)
|
| Title | Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score |
|---|---|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 375 | 86 |
| Week 4 |
-30.21
(27.47)
|
-26.03
(24.50)
|
| Week 8 |
-32.67
(26.85)
|
-28.79
(23.07)
|
| Week 12 |
-35.63
(26.19)
|
-31.16
(25.32)
|
| Week 24 |
-36.94
(27.23)
|
-31.76
(25.09)
|
| Week 36 |
-39.40
(26.77)
|
-33.73
(25.82)
|
| Week 52 |
-42.91
(25.90)
|
-36.58
(24.74)
|
| Title | Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score |
|---|---|
| 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 | Weeks 4, 8, 12, 24, 36 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 399 | 86 |
| Week 4 |
-37.07
(20.75)
|
-30.65
(24.09)
|
| Week 8 |
-39.29
(20.30)
|
-35.32
(22.36)
|
| Week 12 |
-42.23
(20.20)
|
-37.37
(22.14)
|
| Week 24 |
-44.40
(20.94)
|
-41.11
(23.86)
|
| Week 36 |
-45.52
(20.76)
|
-43.13
(24.14)
|
| Week 52 |
-48.57
(19.99)
|
-44.81
(23.85)
|
| Title | Change From Baseline in C-Reactive Protein (CRP) Levels |
|---|---|
| Description | C-reactive protein is a biological marker of inflammation and is measured in milligrams per decilitre (mg/dL) |
| Time Frame | Weeks 4, 8, 12, 24, 36 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 398 | 84 |
| Week 4 |
-0.95
(2.18)
|
-1.09
(3.10)
|
| Week 8 |
-1.02
(2.41)
|
-1.58
(2.60)
|
| Week 12 |
-1.03
(2.21)
|
-1.40
(3.38)
|
| Week 24 |
-1.03
(2.48)
|
-1.46
(2.99)
|
| Week 36 |
-1.11
(2.44)
|
-1.56
(3.04)
|
| Week 52 |
-1.12
(2.55)
|
-1.81
(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 | Weeks 4, 8, 12, 24, 36 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 360 | 81 |
| Week 4 |
-0.70
(0.64)
|
-0.55
(0.56)
|
| Week 8 |
-0.77
(0.65)
|
-0.59
(0.62)
|
| Week 12 |
-0.80
(0.67)
|
-0.60
(0.59)
|
| Week 24 |
-0.83
(0.66)
|
-0.63
(0.58)
|
| Week 36 |
-0.89
(0.63)
|
-0.62
(0.66)
|
| Week 52 |
-0.98
(0.64)
|
-0.69
(0.62)
|
| 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 | Weeks 12, 24 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 356 | 83 |
| Week 12 (Physical Component Score change) |
11.35
(9.13)
|
8.22
(8.73)
|
| Week 12 (Mental Component Score change) |
6.52
(12.98)
|
4.74
(11.53)
|
| Week 24 (Physical Component Score change) |
12.31
(9.12)
|
8.28
(8.53)
|
| Week 24 (Mental Component Score change) |
6.63
(13.23)
|
6.08
(11.76)
|
| Week 52 (Physical Component Score change) |
13.89
(9.32)
|
10.42
(8.94)
|
| Week 52 (Mental Component Score change) |
7.00
(13.81)
|
6.77
(11.60)
|
| 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 | Weeks 12, 24 and 52 |
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 actually collected is indicated for each time point. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 350 | 83 |
| Week 12 |
11.44
(10.36)
|
9.28
(8.51)
|
| Week 24 |
11.74
(10.75)
|
10.41
(8.51)
|
| Week 52 |
12.87
(10.58)
|
10.87
(9.25)
|
| Title | Area Under the Concentration Time Curve (AUC) of GDC-0853 at Steady State (AUC,ss) |
|---|---|
| Description | Population PK model estimated AUC of GDC-0853 at steady-state. AUC was measured in Nanograms (ng) per millilitre(mL)*hour (hr). |
| Time Frame | Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-Evaluable population was defined as all participants that received any fenebrutinib/GDC-0853 and had sufficient data to enable estimation of key PK parameters. Participants who received incorrect therapy different from the intended therapy were summarized in the group according to the therapy actually received. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 388 | 81 |
| Mean (Standard Deviation) [Ng/mL*(hr)] |
13400
(6930)
|
15600
(7850)
|
| Title | Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss) |
|---|---|
| Description | Population PK model estimated minimal plasma concentration (Ctrough) of GDC-0853 at steady-state (ss). |
| Time Frame | Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-Evaluable population was defined as all participants that received any fenebrutinib/GDC-0853 and had sufficient data to enable estimation of key PK parameters. Participants who received incorrect therapy different from the intended therapy were summarized in the group according to the therapy actually received. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 388 | 81 |
| Mean (Standard Deviation) [ng/mL] |
387
(244)
|
467
(285)
|
| Title | Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss) |
|---|---|
| Description | Population PK model estimated plasma decay half life of GDC-0853 at steady-state. |
| Time Frame | Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-Evaluable population was defined as all participants that received any fenebrutinib/GDC-0853 and had sufficient data to enable estimation of key PK parameters. Participants who received incorrect therapy different from the intended therapy were summarized in the group according to the therapy actually received. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 388 | 81 |
| Mean (Standard Deviation) [hr] |
7.94
(3.16)
|
9.01
(4.9)
|
| Title | Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss) |
|---|---|
| Description | Population PK model estimated apparent oral clearance of GDC-0853 at steady-state. |
| Time Frame | Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK-Evaluable population was defined as all participants that received any fenebrutinib/GDC-0853 and had sufficient data to enable estimation of key PK parameters. Participants who received incorrect therapy different from the intended therapy were summarized in the group according to the therapy actually received. |
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 |
|---|---|---|
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. |
| Measure Participants | 388 | 81 |
| Mean (Standard Deviation) [L/hr] |
39.5
(12.6)
|
35.3
(10.3)
|
Adverse Events
| Time Frame | Day 1 up until 8 weeks after the last dose of study drug (up to 1 year, 2 months). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The Safety-evaluable population was defined as all participants who received any study drug and had at least one assessment of safety. AEs that were entered into the database at the time of the database lock were included in the AE analysis. | |||
| Arm/Group Title | GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 | ||
| Arm/Group Description | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo. | Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo. | ||
All Cause Mortality |
||||
| GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/410 (0.7%) | 0/86 (0%) | ||
Serious Adverse Events |
||||
| GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 26/410 (6.3%) | 4/86 (4.7%) | ||
| Blood and lymphatic system disorders | ||||
| IRON DEFICIENCY ANAEMIA | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Cardiac disorders | ||||
| ATRIAL FIBRILLATION | 0/410 (0%) | 0 | 1/86 (1.2%) | 1 |
| CARDIO-RESPIRATORY ARREST | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Gastrointestinal disorders | ||||
| DIARRHOEA | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| ENTEROCOLITIS | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| INFLAMMATORY BOWEL DISEASE | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| INGUINAL HERNIA | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Hepatobiliary disorders | ||||
| CHOLECYSTITIS ACUTE | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Infections and infestations | ||||
| CELLULITIS | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| INFECTION | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| NECROTISING SOFT TISSUE INFECTION | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| OSTEOMYELITIS | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| PNEUMONIA | 0/410 (0%) | 0 | 1/86 (1.2%) | 1 |
| PYELONEPHRITIS | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| URINARY TRACT INFECTION | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| HEAD INJURY | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| HIP FRACTURE | 1/410 (0.2%) | 1 | 1/86 (1.2%) | 1 |
| HUMERUS FRACTURE | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| JOINT DISLOCATION | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| MULTIPLE INJURIES | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| ROAD TRAFFIC ACCIDENT | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Investigations | ||||
| HEPATIC ENZYME INCREASED | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| HYPONATRAEMIA | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| ARTHRITIS | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| OSTEOARTHRITIS | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| RHEUMATOID ARTHRITIS | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| BASAL CELL CARCINOMA | 0/410 (0%) | 0 | 1/86 (1.2%) | 1 |
| LUNG CARCINOMA CELL TYPE UNSPECIFIED STAGE IV | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Nervous system disorders | ||||
| ISCHAEMIC STROKE | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| TRANSIENT ISCHAEMIC ATTACK | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| VERTEBROBASILAR INSUFFICIENCY | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Renal and urinary disorders | ||||
| ACUTE KIDNEY INJURY | 2/410 (0.5%) | 2 | 0/86 (0%) | 0 |
| URETEROLITHIASIS | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| VAGINAL HAEMORRHAGE | 2/410 (0.5%) | 2 | 0/86 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| PLEURAL EFFUSION | 1/410 (0.2%) | 1 | 0/86 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| GDC-0853 (200mg BID) Cohort 1 | GDC-0853 (200mg BID) Cohort 2 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/410 (5.4%) | 4/86 (4.7%) | ||
| Infections and infestations | ||||
| URINARY TRACT INFECTION | 22/410 (5.4%) | 28 | 4/86 (4.7%) | 7 |
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:
NCT02983227
Other Study ID Numbers:
- GA30067
- 2016-000498-19
First Posted:
Dec 6, 2016
Last Update Posted:
Aug 3, 2020
Last Verified:
Jul 1, 2020