A Study in Rheumatoid Arthritis Patients Who Have Completed a Preceding Study With ABBV-105 Given Alone or in Combination With Upadacitinib
Sponsor
AbbVie (Industry)
Overall Status
Terminated
CT.gov ID
NCT03823378
Collaborator
(none)
97
30
6
15.9
3.2
0.2
Study Details
Study Description
Brief Summary
This was a long-term extension (LTE) study to assess the safety, tolerability, and efficacy of ABBV-105 (elsubrutinib [ELS]) and ABBV-599 (ELS 60 mg and upadacitinib [UPA] 15 mg) in participants with rheumatoid arthritis (RA) who completed Study M16-063 (NCT03682705).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This was a Phase 2, double-blind, multicenter, long-term extension (LTE) study to assess the safety, tolerability, and efficacy of 3 doses of ABBV-105 (elsubrutinib [ELS] 5 mg, 20 mg, and 60 mg) and ABBV-599 (ELS 60 mg and upadacitinib [UPA] 15 mg) in adults with active rheumatoid arthritis with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARDs). Participants who successfully completed treatment in the feeder Study M16-063, a Phase 2 dose exploratory study, were eligible to participate in this study. Those who met eligibility criteria and entered this study receiving ELS, ABBV-599, or UPA from Study M16-063 continued on their previously assigned treatment through termination of this study. Participants originally randomized to placebo in Study M16-063 rolled over to ABBV-599 in a blinded fashion in this study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
97 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Double-Blind, Parallel Group Long Term Extension Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial With ABBV-105 Given Alone or in Combination With Upadacitinib (ABBV-599)
Actual Study Start Date
:
May 13, 2019
Actual Primary Completion Date
:
Sep 9, 2020
Actual Study Completion Date
:
Sep 9, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ABBV-599 in M16-063/ABBV-599 in M16-763 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Upadacitinib
Upadacitinib tablet will be administered orally.
Other Names:
|
| Experimental: ABBV-105 60 mg/UPA placebo 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Placebo for upadacitinib
Upadacitinib placebo tablet will be administered orally.
|
| Experimental: ABBV-105 20 mg/UPA placebo 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Placebo for upadacitinib
Upadacitinib placebo tablet will be administered orally.
|
| Experimental: ABBV-105 5 mg/UPA placebo 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Placebo for upadacitinib
Upadacitinib placebo tablet will be administered orally.
|
| Experimental: UPA 15 mg/ABBV-105 placebo 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks |
Drug: Upadacitinib
Upadacitinib tablet will be administered orally.
Other Names:
Drug: Placebo for elsubrutinib
Placebo capsule for elsubrutinib will be administered orally.
|
| Experimental: Placebo in M16-063/ABBV-599 in M16-763 Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Upadacitinib
Upadacitinib tablet will be administered orally.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (AEs) [On or after the first dose of study drug in Study M16-763, and up to 30 days after the last dose of study drug in Study M16-763, up to 52 weeks]
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug as either having a reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug.
Secondary Outcome Measures
- Change in Disease Activity Score 28 C-reactive Protein (DAS28-CRP) From Baseline of Study M16-063 at Each Study Visit in Study M16-763 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP) [Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.
- Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP) [Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical Remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.
- Change in Clinical Disease Activity Index (CDAI) From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria [Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Low Disease Activity (LDA) based on CDAI is defined as achieving a total CDAI score of less than or equal to 10.
- Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria [Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Complete Remission (CR) based on CDAI is defined as achieving a total CDAI score of less than or equal to 2.8.
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 20% response (ACR20) criteria: ≥ 20% improvement in 68-tender joint count from Baseline of Study M16-063 ≥ 20% improvement in 66-swollen joint count from Baseline of Study M16-063 and ≥ 20% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]) Patient's Global Assessment of Disease Activity (PtGA) Physician's Global Assessment of Disease Activity (PhGA) Health Assessment Questionnaire Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP)
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 50% response (ACR50) criteria: ≥ 50% improvement in 68-tender joint count from Baseline of Study M16-063 ≥ 50% improvement in 66-swollen joint count from Baseline of Study M16-063 and ≥ 50% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]) Patient's Global Assessment of Disease Activity (PtGA) Physician's Global Assessment of Disease Activity (PhGA) Health Assessment Questionnaire Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP)
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 70% response (ACR70) criteria: ≥ 70% improvement in 68-tender joint count from Baseline of Study M16-063 ≥ 70% improvement in 66-swollen joint count from Baseline of Study M16-063 and ≥ 70% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]) Patient's Global Assessment of Disease Activity (PtGA) Physician's Global Assessment of Disease Activity (PhGA) Health Assessment Questionnaire Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP)
- Change in Swollen Joint Count 66 (SJC66) From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.
- Change in Tender Joint Count 68 (TJC68) From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.
- Change in Participant's Assessment of Pain (Visual Analog Scale [VAS]) From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
Participants rated their pain on a visual analogue scale (VAS) of 0 to 100 (mm), with 0 representing no pain and 100 representing the worst possible pain. Negative values indicate improvement from baseline.
- Change in Patient's Global Assessment of Disease Activity (PtGA) From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.
- Change in Physician's Global Assessment of Disease Activity (PhGA) From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
The physician assessed a participant's disease activity at the time of the visit using a Physician's Global Assessment of Disease visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.
- Change in Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from baseline in the overall score indicates improvement.
- Change in High-Sensitivity C-Reactive Protein (Hs-CRP) From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
C-reactive protein is a blood test marker for inflammation in the body, and levels rise in response to inflammation. A negative change from baseline indicates improvement.
- Change in Morning Stiffness Severity From Baseline of Study M16-063 [Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763]
Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Participant has completed Study M16-063
-
Participant has not developed any laboratory or clinical discontinuation criteria as defined in the Study M16-063 protocol
-
Participant is willing and/or able to comply with procedures required in the current study protocol
Exclusion Criteria:
-
Participant is currently enrolled or planning to enroll in another interventional clinical study while participating in this study (except the preceding study M16-063)
-
Participant requires vaccination with any live vaccine during study participation, including at least 30 days after the last dose of study drug
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cliniques Universitaires Saint Luc /ID# 207719 | Woluwe-Saint-Lambert | Bruxelles-Capitale | Belgium | 1200 |
| 2 | UZ Leuven /ID# 207722 | Leuven | Belgium | 3000 | |
| 3 | Rheumatology Research Assoc /ID# 207769 | Edmonton | Alberta | Canada | T5M 0H4 |
| 4 | Manitoba Clinic /ID# 206852 | Winnipeg | Manitoba | Canada | R3A 1M3 |
| 5 | CIADS Research Co Ltd /ID# 206853 | Winnipeg | Manitoba | Canada | R3N 0K6 |
| 6 | Mount Sinai Hosp.-Toronto /ID# 206851 | Toronto | Ontario | Canada | M5G 1X5 |
| 7 | Dr. Latha Naik /ID# 213440 | Saskatoon | Saskatchewan | Canada | S7K 3H3 |
| 8 | Revmatolog s.r.o. /ID# 209941 | Jihlava 1 | Jihlava | Czechia | 586 01 |
| 9 | Revmatologicky ustav Praha /ID# 209943 | Prague 2 | Praha 2 | Czechia | 128 00 |
| 10 | Revmatologie MUDr. Klara Sirova /ID# 209944 | Ostrava | Czechia | 702 00 | |
| 11 | CCR Czech a.s /ID# 209942 | Pardubice | Czechia | 530 02 | |
| 12 | CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 208186 | Miskolc | Borsod-Abauj-Zemplen | Hungary | 3529 |
| 13 | Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatokorhaz /ID# 208184 | Nyíregyháza | Szabolcs-Szatmar-Bereg | Hungary | 4400 |
| 14 | Revita Reumatologiai Rendelo /ID# 208187 | Budapest | Hungary | 1027 | |
| 15 | CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 208188 | Szekesfehervar | Hungary | 8000 | |
| 16 | Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 208185 | Veszprem | Hungary | 8200 | |
| 17 | Malopolskie Centrum Kliniczne /ID# 209902 | Cracow | Malopolskie | Poland | 30-149 |
| 18 | McBk Sc /Id# 212577 | Grodzisk Mazowiecki | Mazowieckie | Poland | 05-825 |
| 19 | NBR Polska /ID# 209904 | Warsaw | Mazowieckie | Poland | 00-465 |
| 20 | ClinicMed Daniluk, Nowak Sp.j. /ID# 212578 | Białystok | Podlaskie | Poland | 15-879 |
| 21 | Reumatika - Centrum Reumatologii NZOZ /ID# 209903 | Warsaw | Poland | 02-691 | |
| 22 | Hospital Universitario A Coruña - CHUAC /ID# 207732 | A Coruña | A Coruna | Spain | 15006 |
| 23 | Hospital Unversitario Marques de Valdecilla /ID# 207729 | Santander | Cantabria | Spain | 39008 |
| 24 | Hospital Regional de Malaga /ID# 207735 | Málaga | Malaga | Spain | 29010 |
| 25 | Hospital Clinic /ID# 207740 | Barcelona | Spain | 08036 | |
| 26 | Hospital Universitario Basurto /ID# 207737 | Bilbao | Spain | 48013 | |
| 27 | Hospital Universitario Virgen de las Nieves /ID# 209975 | Granada | Spain | 18014 | |
| 28 | Hospital Clinico Universitario San Carlos /ID# 207738 | Madrid | Spain | 28040 | |
| 29 | Hospital Universitario y Politecnico La Fe /ID# 207739 | Valencia | Spain | 46026 | |
| 30 | University of Oxford /ID# 210571 | Oxford | United Kingdom | OX3 7LF |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: AbbVie Inc., AbbVie
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT03823378
Other Study ID Numbers:
- M16-763
- 2018-002306-31
First Posted:
Jan 30, 2019
Last Update Posted:
Sep 16, 2021
Last Verified:
Aug 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by AbbVie
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | All randomized participants |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Period Title: Overall Study | ||||||
| STARTED | 28 | 16 | 12 | 12 | 20 | 9 |
| COMPLETED | 7 | 0 | 2 | 2 | 2 | 1 |
| NOT COMPLETED | 21 | 16 | 10 | 10 | 18 | 8 |
Baseline Characteristics
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 | Total of all reporting groups |
| Overall Participants | 28 | 16 | 12 | 12 | 20 | 9 | 97 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
57.5
(12.64)
|
58.6
(8.75)
|
58.5
(12.07)
|
54.5
(12.21)
|
61.7
(8.99)
|
59.4
(9.48)
|
58.5
(10.89)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
18
64.3%
|
14
87.5%
|
12
100%
|
8
66.7%
|
18
90%
|
7
77.8%
|
77
79.4%
|
| Male |
10
35.7%
|
2
12.5%
|
0
0%
|
4
33.3%
|
2
10%
|
2
22.2%
|
20
20.6%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||
| White |
27
96.4%
|
15
93.8%
|
12
100%
|
12
100%
|
20
100%
|
9
100%
|
95
97.9%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| American Indian or Alaska Native |
0
0%
|
1
6.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1%
|
| Native Hawaiian or other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
1
3.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1%
|
| Duration of Rheumatoid Arthritis Diagnosis (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
10.024
(5.6087)
|
14.212
(9.0327)
|
5.435
(3.2458)
|
9.466
(6.6508)
|
13.571
(7.8086)
|
9.684
(5.6087)
|
10.778
(7.0861)
|
Outcome Measures
| Title | Number of Participants With Adverse Events (AEs) |
|---|---|
| Description | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug as either having a reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug. |
| Time Frame | On or after the first dose of study drug in Study M16-763, and up to 30 days after the last dose of study drug in Study M16-763, up to 52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 28 | 16 | 12 | 12 | 20 | 9 |
| Count of Participants [Participants] |
11
39.3%
|
10
62.5%
|
3
25%
|
5
41.7%
|
7
35%
|
3
33.3%
|
| Title | Change in Disease Activity Score 28 C-reactive Protein (DAS28-CRP) From Baseline of Study M16-063 at Each Study Visit in Study M16-763 |
|---|---|
| Description | The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 26 | 15 | 7 | 10 | 18 | 8 |
| Week 18 |
-3.27
|
-1.98
|
-1.93
|
-2.55
|
-3.88
|
-2.87
|
| Week 24 |
-3.43
|
-2.62
|
-2.02
|
-3.20
|
-4.02
|
-3.61
|
| Week 30 |
-3.17
|
-2.37
|
-1.45
|
-3.30
|
-3.84
|
-4.08
|
| Week 36 |
-3.45
|
-3.12
|
-1.63
|
-3.00
|
-4.15
|
-3.77
|
| Week 48 |
-3.55
|
-2.77
|
-1.68
|
-3.16
|
-4.38
|
-3.86
|
| Week 60 |
-4.06
|
-3.21
|
-2.55
|
-3.41
|
-4.12
|
-3.69
|
| Title | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP) |
|---|---|
| Description | The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2. |
| Time Frame | Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 27 | 15 | 9 | 10 | 18 | 8 |
| Week 18 |
78.3
279.6%
|
26.7
166.9%
|
44.4
370%
|
20.0
166.7%
|
77.8
389%
|
62.5
694.4%
|
| Week 24 |
77.8
277.9%
|
53.8
336.3%
|
44.4
370%
|
50.0
416.7%
|
88.2
441%
|
85.7
952.2%
|
| Week 30 |
78.3
279.6%
|
76.9
480.6%
|
28.6
238.3%
|
60.0
500%
|
87.5
437.5%
|
100
1111.1%
|
| Week 36 |
87.5
312.5%
|
87.5
546.9%
|
25.0
208.3%
|
40.0
333.3%
|
91.7
458.5%
|
100
1111.1%
|
| Week 48 |
77.8
277.9%
|
66.7
416.9%
|
50.0
416.7%
|
37.5
312.5%
|
87.5
437.5%
|
100
1111.1%
|
| Week 60 |
100
357.1%
|
50.0
312.5%
|
100
833.3%
|
60.0
500%
|
100
500%
|
75.0
833.3%
|
| Title | Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP) |
|---|---|
| Description | The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical Remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6. |
| Time Frame | Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 27 | 15 | 9 | 10 | 18 | 8 |
| Week 18 |
56.5
201.8%
|
20.0
125%
|
11.1
92.5%
|
20.0
166.7%
|
77.8
389%
|
50.0
555.6%
|
| Week 24 |
70.4
251.4%
|
53.8
336.3%
|
33.3
277.5%
|
30.0
250%
|
70.6
353%
|
71.4
793.3%
|
| Week 30 |
65.2
232.9%
|
46.2
288.8%
|
0
0%
|
40.0
333.3%
|
87.5
437.5%
|
100
1111.1%
|
| Week 36 |
66.7
238.2%
|
62.5
390.6%
|
0
0%
|
20.0
166.7%
|
75.0
375%
|
66.7
741.1%
|
| Week 48 |
72.2
257.9%
|
66.7
416.9%
|
0
0%
|
25.0
208.3%
|
62.5
312.5%
|
83.3
925.6%
|
| Week 60 |
77.8
277.9%
|
50.0
312.5%
|
50.0
416.7%
|
0
0%
|
60.0
300%
|
75.0
833.3%
|
| Title | Change in Clinical Disease Activity Index (CDAI) From Baseline of Study M16-063 |
|---|---|
| Description | The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 26 | 15 | 7 | 9 | 17 | 8 |
| Week 18 |
-33.68
|
-23.77
|
-19.16
|
-27.00
|
-36.01
|
-28.65
|
| Week 24 |
-33.47
|
-27.20
|
-19.84
|
-35.59
|
-38.27
|
-32.93
|
| Week 30 |
-32.07
|
-22.40
|
-16.72
|
-35.92
|
-36.86
|
-34.00
|
| Week 36 |
-35.28
|
-28.86
|
-19.17
|
-33.99
|
-42.20
|
-32.92
|
| Week 48 |
-36.26
|
-22.58
|
-18.87
|
-34.77
|
-45.69
|
-35.72
|
| Week 60 |
-37.99
|
-29.70
|
-24.95
|
-37.20
|
-43.98
|
-34.38
|
| Title | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria |
|---|---|
| Description | The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Low Disease Activity (LDA) based on CDAI is defined as achieving a total CDAI score of less than or equal to 10. |
| Time Frame | Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 27 | 15 | 9 | 10 | 18 | 8 |
| Week 18 |
82.6
295%
|
40.0
250%
|
44.4
370%
|
50.0
416.7%
|
77.8
389%
|
62.5
694.4%
|
| Week 24 |
88.9
317.5%
|
69.2
432.5%
|
55.6
463.3%
|
80.0
666.7%
|
88.2
441%
|
100
1111.1%
|
| Week 30 |
78.3
279.6%
|
76.9
480.6%
|
42.9
357.5%
|
80.0
666.7%
|
81.3
406.5%
|
100
1111.1%
|
| Week 36 |
86.4
308.6%
|
87.5
546.9%
|
75.0
625%
|
70.0
583.3%
|
83.3
416.5%
|
100
1111.1%
|
| Week 48 |
77.8
277.9%
|
66.7
416.9%
|
75.0
625%
|
62.5
520.8%
|
87.5
437.5%
|
100
1111.1%
|
| Week 60 |
100
357.1%
|
50.0
312.5%
|
100
833.3%
|
80.0
666.7%
|
80.0
400%
|
75.0
833.3%
|
| Title | Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria |
|---|---|
| Description | The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Complete Remission (CR) based on CDAI is defined as achieving a total CDAI score of less than or equal to 2.8. |
| Time Frame | Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 27 | 15 | 9 | 10 | 18 | 8 |
| Week 18 |
17.4
62.1%
|
13.3
83.1%
|
11.1
92.5%
|
12.5
104.2%
|
55.6
278%
|
25.0
277.8%
|
| Week 24 |
29.6
105.7%
|
23.1
144.4%
|
11.1
92.5%
|
10.0
83.3%
|
58.8
294%
|
50.0
555.6%
|
| Week 30 |
26.1
93.2%
|
30.8
192.5%
|
14.3
119.2%
|
30.0
250%
|
43.8
219%
|
87.5
972.2%
|
| Week 36 |
36.4
130%
|
25.0
156.3%
|
25.0
208.3%
|
10.0
83.3%
|
41.7
208.5%
|
50.0
555.6%
|
| Week 48 |
44.4
158.6%
|
33.3
208.1%
|
0
0%
|
12.5
104.2%
|
50.0
250%
|
100
1111.1%
|
| Week 60 |
33.3
118.9%
|
50.0
312.5%
|
50.0
416.7%
|
20.0
166.7%
|
60.0
300%
|
50.0
555.6%
|
| Title | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 20% response (ACR20) criteria: ≥ 20% improvement in 68-tender joint count from Baseline of Study M16-063 ≥ 20% improvement in 66-swollen joint count from Baseline of Study M16-063 and ≥ 20% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]) Patient's Global Assessment of Disease Activity (PtGA) Physician's Global Assessment of Disease Activity (PhGA) Health Assessment Questionnaire Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP) |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 26 | 15 | 7 | 10 | 17 | 8 |
| Week 18 |
90.9
324.6%
|
80.0
500%
|
57.1
475.8%
|
66.7
555.8%
|
88.2
441%
|
75.0
833.3%
|
| Week 24 |
96.2
343.6%
|
92.9
580.6%
|
85.7
714.2%
|
77.8
648.3%
|
93.8
469%
|
100
1111.1%
|
| Week 30 |
86.4
308.6%
|
69.2
432.5%
|
50.0
416.7%
|
80.0
666.7%
|
87.5
437.5%
|
100
1111.1%
|
| Week 36 |
87.0
310.7%
|
87.5
546.9%
|
66.7
555.8%
|
88.9
740.8%
|
91.7
458.5%
|
83.3
925.6%
|
| Week 48 |
94.1
336.1%
|
83.3
520.6%
|
66.7
555.8%
|
85.7
714.2%
|
87.5
437.5%
|
100
1111.1%
|
| Week 60 |
88.9
317.5%
|
100
625%
|
100
833.3%
|
75.0
625%
|
100
500%
|
100
1111.1%
|
| Title | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 50% response (ACR50) criteria: ≥ 50% improvement in 68-tender joint count from Baseline of Study M16-063 ≥ 50% improvement in 66-swollen joint count from Baseline of Study M16-063 and ≥ 50% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]) Patient's Global Assessment of Disease Activity (PtGA) Physician's Global Assessment of Disease Activity (PhGA) Health Assessment Questionnaire Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP) |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 26 | 15 | 10 | 10 | 17 | 8 |
| Week 18 |
68.2
243.6%
|
46.7
291.9%
|
40.0
333.3%
|
40.0
333.3%
|
70.6
353%
|
62.5
694.4%
|
| Week 24 |
76.9
274.6%
|
64.3
401.9%
|
42.9
357.5%
|
66.7
555.8%
|
87.5
437.5%
|
100
1111.1%
|
| Week 30 |
63.6
227.1%
|
61.5
384.4%
|
16.7
139.2%
|
60.0
500%
|
87.5
437.5%
|
100
1111.1%
|
| Week 36 |
82.6
295%
|
62.5
390.6%
|
33.3
277.5%
|
66.7
555.8%
|
75.0
375%
|
66.7
741.1%
|
| Week 48 |
82.4
294.3%
|
66.7
416.9%
|
66.7
555.8%
|
71.4
595%
|
87.5
437.5%
|
83.3
925.6%
|
| Week 60 |
88.9
317.5%
|
50.0
312.5%
|
100
833.3%
|
75.0
625%
|
100
500%
|
100
1111.1%
|
| Title | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 70% response (ACR70) criteria: ≥ 70% improvement in 68-tender joint count from Baseline of Study M16-063 ≥ 70% improvement in 66-swollen joint count from Baseline of Study M16-063 and ≥ 70% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]) Patient's Global Assessment of Disease Activity (PtGA) Physician's Global Assessment of Disease Activity (PhGA) Health Assessment Questionnaire Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP) |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 26 | 15 | 10 | 12 | 18 | 8 |
| Week 18 |
47.8
170.7%
|
33.3
208.1%
|
20.0
166.7%
|
25.0
208.3%
|
55.6
278%
|
37.5
416.7%
|
| Week 24 |
57.7
206.1%
|
42.9
268.1%
|
12.5
104.2%
|
55.6
463.3%
|
62.5
312.5%
|
87.5
972.2%
|
| Week 30 |
63.6
227.1%
|
46.2
288.8%
|
14.3
119.2%
|
60.0
500%
|
68.8
344%
|
87.5
972.2%
|
| Week 36 |
78.3
279.6%
|
50.0
312.5%
|
25.0
208.3%
|
44.4
370%
|
75.0
375%
|
66.7
741.1%
|
| Week 48 |
58.8
210%
|
50.0
312.5%
|
25.0
208.3%
|
42.9
357.5%
|
75.0
375%
|
83.3
925.6%
|
| Week 60 |
88.9
317.5%
|
50.0
312.5%
|
50.0
416.7%
|
25.0
208.3%
|
60.0
300%
|
75.0
833.3%
|
| Title | Change in Swollen Joint Count 66 (SJC66) From Baseline of Study M16-063 |
|---|---|
| Description | Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 28 | 16 | 11 | 12 | 20 | 9 |
| Week 18 |
-11.50
|
-9.88
|
-8.00
|
-13.42
|
-12.80
|
-9.78
|
| Week 24 |
-11.67
|
-10.54
|
-7.67
|
-15.60
|
-13.24
|
-10.38
|
| Week 30 |
-11.87
|
-7.69
|
-5.86
|
-15.50
|
-13.44
|
-10.75
|
| Week 36 |
-12.38
|
-10.13
|
-7.75
|
-14.60
|
-14.25
|
-10.50
|
| Week 48 |
-13.67
|
-8.00
|
-8.00
|
-15.88
|
-15.75
|
-10.67
|
| Week 60 |
-14.44
|
-12.50
|
-7.50
|
-15.40
|
-13.00
|
-11.25
|
| Title | Change in Tender Joint Count 68 (TJC68) From Baseline of Study M16-063 |
|---|---|
| Description | Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 28 | 16 | 11 | 12 | 20 | 9 |
| Week 18 |
-17.29
|
-12.69
|
-9.82
|
-14.17
|
-19.75
|
-10.67
|
| Week 24 |
-17.93
|
-15.77
|
-8.11
|
-20.20
|
-20.76
|
-14.25
|
| Week 30 |
-16.30
|
-9.54
|
-4.57
|
-19.80
|
-20.50
|
-14.88
|
| Week 36 |
-16.42
|
-15.25
|
-8.00
|
-18.40
|
-24.92
|
-14.83
|
| Week 48 |
-17.33
|
-12.33
|
-5.50
|
-18.88
|
-28.88
|
-15.00
|
| Week 60 |
-19.78
|
-19.00
|
-11.50
|
-20.20
|
-26.20
|
-15.50
|
| Title | Change in Participant's Assessment of Pain (Visual Analog Scale [VAS]) From Baseline of Study M16-063 |
|---|---|
| Description | Participants rated their pain on a visual analogue scale (VAS) of 0 to 100 (mm), with 0 representing no pain and 100 representing the worst possible pain. Negative values indicate improvement from baseline. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 26 | 15 | 7 | 10 | 18 | 8 |
| Week 18 |
-49.68
|
-34.67
|
-25.57
|
-32.50
|
-56.17
|
-47.88
|
| Week 24 |
-45.46
|
-48.36
|
-29.43
|
-42.00
|
-57.76
|
-59.38
|
| Week 30 |
-48.18
|
-40.62
|
-20.00
|
-45.90
|
-53.63
|
-60.25
|
| Week 36 |
-49.22
|
-47.13
|
-25.67
|
-46.70
|
-58.83
|
-54.83
|
| Week 48 |
-60.06
|
-49.00
|
-35.00
|
-56.13
|
-58.75
|
-61.50
|
| Week 60 |
-54.67
|
-52.00
|
-45.50
|
-58.80
|
-61.00
|
-55.00
|
| Title | Change in Patient's Global Assessment of Disease Activity (PtGA) From Baseline of Study M16-063 |
|---|---|
| Description | Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 26 | 15 | 7 | 10 | 18 | 8 |
| Week 18 |
-45.18
|
-34.07
|
-28.57
|
-35.70
|
-56.56
|
-40.13
|
| Week 24 |
-48.62
|
-45.93
|
-33.29
|
-45.20
|
-62.47
|
-58.13
|
| Week 30 |
-46.18
|
-39.69
|
-21.40
|
-45.20
|
-56.31
|
-57.75
|
| Week 36 |
-51.70
|
-48.63
|
-31.67
|
-46.20
|
-61.00
|
-53.33
|
| Week 48 |
-54.24
|
-44.00
|
-38.67
|
-53.13
|
-60.75
|
-56.67
|
| Week 60 |
-56.67
|
-56.00
|
-54.50
|
-54.60
|
-59.80
|
-57.00
|
| Title | Change in Physician's Global Assessment of Disease Activity (PhGA) From Baseline of Study M16-063 |
|---|---|
| Description | The physician assessed a participant's disease activity at the time of the visit using a Physician's Global Assessment of Disease visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 27 | 15 | 7 | 9 | 17 | 8 |
| Week 18 |
-57.22
|
-41.00
|
-33.00
|
-35.00
|
-59.06
|
-55.13
|
| Week 24 |
-57.93
|
-48.36
|
-39.43
|
-50.89
|
-61.19
|
-62.38
|
| Week 30 |
-55.04
|
-41.23
|
-41.80
|
-54.78
|
-56.20
|
-63.50
|
| Week 36 |
-57.55
|
-53.75
|
-60.00
|
-54.78
|
-68.45
|
-65.83
|
| Week 48 |
-56.39
|
-36.83
|
-56.67
|
-57.14
|
-66.13
|
-66.40
|
| Week 60 |
-64.33
|
-56.00
|
-65.00
|
-61.50
|
-60.00
|
-56.75
|
| Title | Change in Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline of Study M16-063 |
|---|---|
| Description | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from baseline in the overall score indicates improvement. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 25 | 15 | 7 | 10 | 17 | 8 |
| Week 18 |
-0.57
|
-0.49
|
-0.61
|
-0.61
|
-0.85
|
-0.47
|
| Week 24 |
-0.59
|
-0.46
|
-0.57
|
-0.54
|
-0.59
|
-0.78
|
| Week 30 |
-0.64
|
-0.45
|
-0.15
|
-0.51
|
-0.73
|
-0.75
|
| Week 36 |
-0.67
|
-0.70
|
-0.33
|
-0.30
|
-0.51
|
-0.56
|
| Week 48 |
-0.70
|
-0.63
|
-0.29
|
-0.42
|
-0.39
|
-0.71
|
| Week 60 |
-0.78
|
-0.75
|
-0.31
|
-0.58
|
-0.48
|
-0.72
|
| Title | Change in High-Sensitivity C-Reactive Protein (Hs-CRP) From Baseline of Study M16-063 |
|---|---|
| Description | C-reactive protein is a blood test marker for inflammation in the body, and levels rise in response to inflammation. A negative change from baseline indicates improvement. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 28 | 16 | 11 | 12 | 20 | 9 |
| Week 18 |
-16.04
|
5.34
|
-0.96
|
-14.85
|
-11.48
|
-10.00
|
| Week 24 |
-15.08
|
-0.20
|
-2.18
|
-15.09
|
-9.48
|
-13.16
|
| Week 30 |
-16.61
|
-6.00
|
-1.66
|
-17.11
|
-9.55
|
-16.22
|
| Week 36 |
-13.88
|
-12.43
|
-1.58
|
-13.61
|
-7.76
|
-18.34
|
| Week 48 |
-16.41
|
-18.38
|
-5.99
|
-20.18
|
-7.22
|
-18.30
|
| Week 60 |
-25.69
|
-31.46
|
-3.98
|
-25.58
|
-3.34
|
-12.47
|
| Title | Change in Morning Stiffness Severity From Baseline of Study M16-063 |
|---|---|
| Description | Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline. |
| Time Frame | Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set: all participants who completed Study M16-063 and received at least 1 dose of assigned study drug in Study M16-763 with available data |
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 |
| Measure Participants | 25 | 15 | 7 | 10 | 17 | 8 |
| Week 18 |
-4.27
|
-2.27
|
-2.14
|
-3.40
|
-5.29
|
-2.38
|
| Week 24 |
-4.48
|
-2.64
|
-3.29
|
-3.70
|
-4.88
|
-3.50
|
| Week 30 |
-4.36
|
-2.23
|
-1.20
|
-4.20
|
-4.53
|
-3.13
|
| Week 36 |
-4.43
|
-3.38
|
-1.00
|
-4.00
|
-5.55
|
-3.00
|
| Week 48 |
-5.47
|
-3.33
|
-1.00
|
-4.13
|
-5.38
|
-3.67
|
| Week 60 |
-4.89
|
-4.50
|
-3.00
|
-4.40
|
-4.80
|
-3.00
|
Adverse Events
| Time Frame | All-cause mortality is reported from enrollment to the end of study; median time on follow-up was ABBV-599 in M16-063/M16-763 (279 days); ABBV-105 60 mg/UPA placebo (183 days); ABBV-105 20 mg/UPA placebo (159 days); ABBV-105 5 mg/UPA placebo (337 days); UPA 15 mg/ABBV-105 placebo (229 days); and Placebo in M16-063/ABBV-599 in M16-763 (281 days). TEAEs/SAEs were collected from the first dose in M16-763 until 30 days after last dose, up to 52 weeks. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All-cause mortality and adverse events: all participants who completed Study M16-063 and received at least one dose of assigned study drug in Study M16-763, grouped according to treatments actually received in Study M16-763 | |||||||||||
| Arm/Group Title | ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 | ||||||
| Arm/Group Description | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks | 60 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 20 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 5 mg elsubrutinib capsule once a day by mouth for 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 48 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks; placebo capsule for elsubrutinib once a day by mouth for 48 weeks | Placebo in M16-063; 60 mg elsubrutinib capsule once a day by mouth for 48 weeks and 15 mg film-coated upadacitinib tablet once a day by mouth for 48 weeks in M16-763 | ||||||
All Cause Mortality |
||||||||||||
| ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/28 (0%) | 0/16 (0%) | 0/12 (0%) | 0/12 (0%) | 0/20 (0%) | 0/9 (0%) | ||||||
Serious Adverse Events |
||||||||||||
| ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/28 (3.6%) | 0/16 (0%) | 0/12 (0%) | 0/12 (0%) | 1/20 (5%) | 0/9 (0%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| PERIPROSTHETIC FRACTURE | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| LUNG ADENOCARCINOMA | 1/28 (3.6%) | 1 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| ABBV-599 in M16-063/ABBV-599 in M16-763 | ABBV-105 60 mg/UPA Placebo | ABBV-105 20 mg/UPA Placebo | ABBV-105 5 mg/UPA Placebo | UPA 15 mg/ABBV-105 Placebo | Placebo in M16-063/ABBV-599 in M16-763 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/28 (28.6%) | 10/16 (62.5%) | 3/12 (25%) | 5/12 (41.7%) | 7/20 (35%) | 3/9 (33.3%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| ANAEMIA | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| MICROCYTIC ANAEMIA | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| ABDOMINAL PAIN | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| DIARRHOEA | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| NAUSEA | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| VOMITING | 1/28 (3.6%) | 1 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| General disorders | ||||||||||||
| ASTHENIA | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| DRUG INTOLERANCE | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| DRUG WITHDRAWAL SYNDROME | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 1/9 (11.1%) | 1 |
| INFLUENZA LIKE ILLNESS | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 1/9 (11.1%) | 1 |
| NON-CARDIAC CHEST PAIN | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| PYREXIA | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| Infections and infestations | ||||||||||||
| BRONCHITIS | 1/28 (3.6%) | 1 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| EAR INFECTION | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| GASTROENTERITIS | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| NASOPHARYNGITIS | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| ORAL CANDIDIASIS | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| RESPIRATORY TRACT INFECTION VIRAL | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| TOOTH INFECTION | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| UPPER RESPIRATORY TRACT INFECTION | 3/28 (10.7%) | 3 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 1/12 (8.3%) | 2 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| URETHRITIS | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| URINARY TRACT INFECTION | 1/28 (3.6%) | 1 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 2/20 (10%) | 2 | 1/9 (11.1%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||
| FALL | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| Investigations | ||||||||||||
| URINE ANALYSIS ABNORMAL | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| DIABETES MELLITUS | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| HYPERGLYCAEMIA | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 1/9 (11.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| JOINT SWELLING | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 1/12 (8.3%) | 1 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| RHEUMATOID ARTHRITIS | 2/28 (7.1%) | 2 | 4/16 (25%) | 4 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| BASAL CELL CARCINOMA | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 1/9 (11.1%) | 1 |
| Nervous system disorders | ||||||||||||
| DIZZINESS | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 1/9 (11.1%) | 1 |
| HEADACHE | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 1/12 (8.3%) | 1 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| TREMOR | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| ANXIETY | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| DEPRESSION | 0/28 (0%) | 0 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 1/9 (11.1%) | 1 |
| Renal and urinary disorders | ||||||||||||
| RENAL CYST | 1/28 (3.6%) | 1 | 0/16 (0%) | 0 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 1/20 (5%) | 1 | 0/9 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| DERMATITIS | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
| Vascular disorders | ||||||||||||
| HYPERTENSION | 0/28 (0%) | 0 | 1/16 (6.3%) | 1 | 0/12 (0%) | 0 | 0/12 (0%) | 0 | 0/20 (0%) | 0 | 0/9 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
| abbvieclinicaltrials@abbvie.com |
Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT03823378
Other Study ID Numbers:
- M16-763
- 2018-002306-31
First Posted:
Jan 30, 2019
Last Update Posted:
Sep 16, 2021
Last Verified:
Aug 1, 2021