A Study to Investigate the Safety and Efficacy of ABBV-105 Alone or in Combination With Upadacitinib (ABBV-599 Combination) in Participants With Active Rheumatoid Arthritis
Study Details
Study Description
Brief Summary
This was a phase 2 study to evaluate the safety and efficacy of elsubrutinib (ELS) and ABBV-599 (ELS plus upadacitinib [UPA]) vs placebo on a background of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid arthritis (RA) at 12 weeks in biological disease-modifying anti-rheumatic drugs (bDMARD)-inadequate response (bDMARD-IR) or bDMARD-intolerant participants with moderately to severely active RA and to define optimal dose for further development.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
This was a 12-week, randomized, double-blind, parallel-group, Phase 2, dose exploratory, multicenter study. Participants who met eligibility criteria were randomized in a 3:2:2:2:2:1 ratio to 1 of 6 treatment groups: ABBV-599 [UPA 15 mg/ELS 60 mg]); ELS 60 mg/UPA placebo; ELS 20 mg/UPA placebo; ELS 5 mg/UPA placebo; UPA 15 mg/ELS placebo; and ELS placebo/UPA placebo. The study included a 35-day maximum screening period and a 12-week treatment period with 30-day follow-up.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Placebo Comparator: ELS placebo/UPA placebo Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks |
Drug: Placebo for elsubrutinib
Placebo capsule for elsubrutinib will be administered orally.
Drug: Placebo for upadacitinib
Placebo tablet for upadacitinib will be administered orally.
|
Experimental: UPA 15 mg/ELS 60 mg 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Upadacitinib
Upadacitinib tablet will be administered orally.
Other Names:
|
Experimental: ELS 60 mg/UPA placebo 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Placebo for upadacitinib
Placebo tablet for upadacitinib will be administered orally.
|
Experimental: ELS 20 mg/UPA placebo 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Placebo for upadacitinib
Placebo tablet for upadacitinib will be administered orally.
|
Experimental: ELS 5 mg/UPA placebo 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks |
Drug: Elsubrutinib
Elsubrutinib capsule will be administered orally.
Other Names:
Drug: Placebo for upadacitinib
Placebo tablet for upadacitinib will be administered orally.
|
Experimental: UPA 15 mg/ELS placebo 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Drug: Upadacitinib
Upadacitinib tablet will be administered orally.
Other Names:
Drug: Placebo for elsubrutinib
Placebo capsule for elsubrutinib will be administered orally.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 [Baseline, Week 12]
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.
Secondary Outcome Measures
- Change From Baseline in Clinical Disease Activity Index (CDAI) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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.
- Change From Baseline in Simplified Disease Activity Index (SDAI) [Baseline, Week 2, Week 4, Week 8, and Week 12]
The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global disease activity assessed by the participant on a visual analogue scale from 0 to 10 (cm), global disease activity assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein (CRP; mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86.with higher scores indicating higher disease activity. A negative change from baseline indicates improvement in disease activity.
- Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 [At Week 12]
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.
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 [At Week 12]
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 Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria [Week 2, Week 4, Week 8, and Week 12]
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 CDAI of less than or equal to 10.
- Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria [Week 2, Week 4, Week 8, and Week 12]
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 CDAI of less than or equal to 2.8.
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response [Baseline, Week 2, Week 4, Week 8, and Week 12]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 20% response (ACR20) criteria: ≥ 20% improvement in 68-tender joint count ≥ 20% improvement in 66-swollen joint count and ≥ 20% improvement in at least 3 of the 5 following parameters: 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, Week 2, Week 4, Week 8, and Week 12]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 50% response (ACR50) criteria: ≥ 50% improvement in 68-tender joint count ≥ 50% improvement in 66-swollen joint count and ≥ 50% improvement in at least 3 of the 5 following parameters: 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, Week 2, Week 4, Week 8, and Week 12]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the American College of Rheumatology 70% response (ACR70) criteria: ≥ 70% improvement in 68-tender joint count ≥ 70% improvement in 66-swollen joint count and ≥ 70% improvement in at least 3 of the 5 following parameters: 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 From Baseline in Tender Joint Count 68 (TJC68) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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 From Baseline in Swollen Joint Count 66 (SJC66) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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 From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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 From Baseline in Patient's Global Assessment of Disease Activity (PGA) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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 From Baseline in Physician's Global Assessment of Disease Activity (PhGA) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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 From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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 From Baseline in High-Sensitivity C-reactive Protein (hsCRP) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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 in indicates improvement.
- Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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.
- Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) [Baseline, Week 2, Week 4, Week 8, and Week 12]
The DAS28-ESR is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 100 mm) are included in the DAS28 -ESR score. Scores on the DAS28-ESR range from 0 to 10; higher scores indicate more disease activity.
- Change From Baseline in Morning Stiffness Severity [Baseline, Week 2, Week 4, Week 8, and Week 12]
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.
- Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) [Baseline, Week 2, Week 4, Week 8, and Week 12]
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. The minimal clinically important difference (MCID) in HAQ-DI is defined as change from Baseline ≤ -0.22 for rheumatoid arthritis.
- Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission [Baseline, Week 2, Week 4, Week 8, and Week 12]
The EULAR Boolean-based definition of remission is as follows: at any time point, a participant must satisfy all of the following: tender joint count ≤1, swollen joint count ≤1, C-reactive protein ≤1 mg/dl and Patient Global Assessment (PGA) ≤1 (on a 0-10 scale).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months based on the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA
-
Participant meets the following minimum disease activity criteria:
-
≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits
-
High-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L (central lab) at Screening Visit
-
Participants must have been treated for ≥ 3 months with ≥ 1 biologic disease-modifying anti-rheumatic drug (bDMARD) therapy but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration
-
Participants must have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug
-
Participants must have discontinued all bDMARDs prior to the first dose of study drug
Exclusion Criteria:
- Participant has prior exposure to any Janus Kinase (JAK) inhibitor for greater than 2 weeks (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib). A washout period of ≥ 30 days is required for any JAK inhibitor prior to the first dose of study drug.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Rheum Assoc of North Alabama /ID# 167382 | Huntsville | Alabama | United States | 35801 |
2 | AZ Arthritis & Rheum Research /ID# 167446 | Mesa | Arizona | United States | 85210 |
3 | SunValley Arthritis Center, Lt /ID# 213073 | Peoria | Arizona | United States | 85381 |
4 | AZ Arthritis and Rheum Researc /ID# 167448 | Phoenix | Arizona | United States | 85032 |
5 | St. Joseph Heritage Healthcare /ID# 167379 | Fullerton | California | United States | 92835 |
6 | Purushotham, Akther & Roshan K /ID# 168121 | La Mesa | California | United States | 91942 |
7 | Valerius Medical Group /ID# 168123 | Los Alamitos | California | United States | 90720 |
8 | Sierra Rheumatology /ID# 167976 | Roseville | California | United States | 95661 |
9 | Rheumatology Center of San Diego /ID# 170690 | San Diego | California | United States | 92128-2549 |
10 | Iraj Sabahi Research, Inc /ID# 201923 | Turlock | California | United States | 95382-2007 |
11 | Inland Rheum Clin Trials Inc. /ID# 167459 | Upland | California | United States | 91786 |
12 | Medvin Clinical Research /ID# 205731 | Whittier | California | United States | 90606 |
13 | Rheumatology Consultants of De /ID# 208238 | Lewes | Delaware | United States | 19958 |
14 | Bay Area Arthritis and Osteo /ID# 208111 | Brandon | Florida | United States | 33511 |
15 | Clinical Res of West FL, Inc. /ID# 167462 | Clearwater | Florida | United States | 33765 |
16 | Omega Research Maitland, LLC /ID# 167376 | DeBary | Florida | United States | 32713-2260 |
17 | Riverside Clinical Research /ID# 167982 | Edgewater | Florida | United States | 32132 |
18 | Lakes Research, LLC /ID# 170660 | Miami | Florida | United States | 33014 |
19 | Kendall South Medical Center, Inc. /ID# 206857 | Miami | Florida | United States | 33185-5948 |
20 | Medallion Clinical Research Institute, LLC /ID# 201710 | Naples | Florida | United States | 34102 |
21 | Rheum Assoc of Central FL /ID# 170858 | Orlando | Florida | United States | 32806 |
22 | HMD Research LLC /ID# 208381 | Orlando | Florida | United States | 32819 |
23 | International Medical Research - Ormond /ID# 170864 | Ormond Beach | Florida | United States | 32174 |
24 | Millennium Research /ID# 167453 | Ormond Beach | Florida | United States | 32174 |
25 | Arthritis Center, Inc. /ID# 170695 | Palm Harbor | Florida | United States | 34684 |
26 | Integral Rheumatology & Immunology Specialists /ID# 206724 | Plantation | Florida | United States | 33324 |
27 | BayCare Medical Group /ID# 170860 | Saint Petersburg | Florida | United States | 33705 |
28 | St. Anthony Comprehensive Rese /ID# 170668 | Saint Petersburg | Florida | United States | 33705 |
29 | Clinical Research of West Florida, Inc /ID# 169099 | Tampa | Florida | United States | 33606-1246 |
30 | ForCare Clinical Research /ID# 206280 | Tampa | Florida | United States | 33613-1244 |
31 | Florida Medical Clinic /ID# 206279 | Zephyrhills | Florida | United States | 33542 |
32 | Institute of Arthritis Researc /ID# 170694 | Idaho Falls | Idaho | United States | 83404 |
33 | Great Lakes Clinical Trials /ID# 167471 | Chicago | Illinois | United States | 60640 |
34 | Clinical Investigation Specialists - Skokie /ID# 167468 | Skokie | Illinois | United States | 60076 |
35 | Deerbrook Medical Associates /ID# 207098 | Vernon Hills | Illinois | United States | 60061 |
36 | PRN of Kansas /ID# 167985 | Wichita | Kansas | United States | 67205 |
37 | The Arthritis & Diabetes Clinic, Inc. /ID# 170682 | Monroe | Louisiana | United States | 71203 |
38 | Mansfield Health Center /ID# 167372 | Mansfield | Massachusetts | United States | 02048 |
39 | Advanced Clinical Care /ID# 167367 | Worcester | Massachusetts | United States | 01605 |
40 | June DO, PC /ID# 170670 | Lansing | Michigan | United States | 48910 |
41 | Beals Instititute /ID# 170658 | Lansing | Michigan | United States | 48917 |
42 | Arthritis Associates /ID# 209075 | Hattiesburg | Mississippi | United States | 39402 |
43 | North Mississippi Med Clinics /ID# 167377 | Tupelo | Mississippi | United States | 38801 |
44 | Clayton Medical Associates dba Saint Louis Rheumatology /ID# 170650 | Saint Louis | Missouri | United States | 63119-3845 |
45 | Physician Research Collaboration, LLC /ID# 200480 | Lincoln | Nebraska | United States | 68516 |
46 | Dhmc /Id# 167476 | Lebanon | New Hampshire | United States | 03756 |
47 | Ocean Rheumatology /ID# 170673 | Toms River | New Jersey | United States | 08755 |
48 | Arthritis and Osteo Assoc /ID# 167443 | Las Cruces | New Mexico | United States | 88011 |
49 | DJL Clinical Research, PLLC /ID# 167374 | Charlotte | North Carolina | United States | 28210-8508 |
50 | EmergeOrtho, P.A. /ID# 209154 | Durham | North Carolina | United States | 27704 |
51 | Cape Fear Arthritis Care /ID# 167413 | Leland | North Carolina | United States | 28451 |
52 | New Horizons Clinical Research /ID# 170862 | Blue Ash | Ohio | United States | 45242-3763 |
53 | Marietta Memorial Hospital /ID# 210968 | Marietta | Ohio | United States | 45750-1635 |
54 | STAT Research, Inc. /ID# 200485 | Vandalia | Ohio | United States | 45377-9464 |
55 | Health Research of Oklahoma /ID# 167370 | Oklahoma City | Oklahoma | United States | 73103-2400 |
56 | Clinical Research Ctr Reading /ID# 170708 | Wyomissing | Pennsylvania | United States | 19610 |
57 | West Tennessee Research Inst /ID# 167366 | Jackson | Tennessee | United States | 38305 |
58 | Nashville Arthritis and Rheumatology /ID# 206699 | Nashville | Tennessee | United States | 37203 |
59 | Amarillo Ctr for Clin Research /ID# 200484 | Amarillo | Texas | United States | 79124 |
60 | Tekton Research, Inc. /ID# 167475 | Austin | Texas | United States | 78745 |
61 | Trinity Universal Res Assoc /ID# 209252 | Carrollton | Texas | United States | 75007 |
62 | Arth and Osteo Clin Brazo Valley /ID# 209401 | College Station | Texas | United States | 77845 |
63 | Metroplex Clinical Research /ID# 167458 | Dallas | Texas | United States | 75231 |
64 | Rheumatic Disease Clin Res Ctr /ID# 167474 | Houston | Texas | United States | 77004 |
65 | Rheumatology Clinic of Houston /ID# 203689 | Houston | Texas | United States | 77065 |
66 | Accurate Clinical Research /ID# 207059 | Houston | Texas | United States | 77089 |
67 | West Texas Clinical Research /ID# 205732 | Lubbock | Texas | United States | 79410-1198 |
68 | SW Rheumatology Res. LLC /ID# 167383 | Mesquite | Texas | United States | 75150 |
69 | Trinity Universal Research Association /ID# 209253 | Plano | Texas | United States | 75024-5283 |
70 | Sun Research Institute /ID# 170667 | San Antonio | Texas | United States | 78215 |
71 | Accurate Clinical Management /ID# 200481 | San Antonio | Texas | United States | 78229 |
72 | DM Clinical Research /ID# 167444 | Tomball | Texas | United States | 77375 |
73 | Arthritis & Osteoporosis Clinic /ID# 167407 | Waco | Texas | United States | 76710 |
74 | Tidewater Physicians Medical Center /ID# 210884 | Newport News | Virginia | United States | 23606-4434 |
75 | Western Washington Arthritis C /ID# 205821 | Bothell | Washington | United States | 98021 |
76 | Arthritis Northwest, PLLC /ID# 200479 | Spokane | Washington | United States | 99204 |
77 | Rheumatology and Pulmonary cli /ID# 170863 | Beckley | West Virginia | United States | 25801 |
78 | Aurora Rheumatology and Immunotherapy Center /ID# 167385 | Franklin | Wisconsin | United States | 53132 |
79 | CUB Hospital Erasme /ID# 201965 | Brussels | Bruxelles-Capitale | Belgium | 1070 |
80 | Cliniques Universitaires Saint Luc /ID# 201756 | Woluwe-Saint-Lambert | Bruxelles-Capitale | Belgium | 1200 |
81 | UZ Ghent /ID# 201757 | Ghent | Oost-Vlaanderen | Belgium | 9000 |
82 | UZ Leuven /ID# 201927 | Leuven | Belgium | 3000 | |
83 | Rheumatology Research Assoc /ID# 207299 | Edmonton | Alberta | Canada | T5M 0H4 |
84 | Manitoba Clinic /ID# 202126 | Winnipeg | Manitoba | Canada | R3A 1M3 |
85 | CIADS Research Co Ltd /ID# 202125 | Winnipeg | Manitoba | Canada | R3N 0K6 |
86 | Credit Valley Rheumatology /ID# 202124 | Mississauga | Ontario | Canada | L5M 2V8 |
87 | Mount Sinai Hosp.-Toronto /ID# 202652 | Toronto | Ontario | Canada | M5G 1X5 |
88 | Dr. Latha Naik /ID# 212972 | Saskatoon | Saskatchewan | Canada | S7K 3H3 |
89 | Revmatolog s.r.o. /ID# 202610 | Jihlava 1 | Jihlava | Czechia | 586 01 |
90 | Revmatologicky ustav Praha /ID# 202142 | Prague 2 | Praha 2 | Czechia | 128 00 |
91 | Revmatologie MUDr. Klara Sirova /ID# 205185 | Ostrava | Czechia | 702 00 | |
92 | CCR Czech a.s /ID# 202144 | Pardubice | Czechia | 530 02 | |
93 | CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 202439 | Miskolc | Borsod-Abauj-Zemplen | Hungary | 3529 |
94 | Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatokorhaz /ID# 202441 | Nyíregyháza | Szabolcs-Szatmar-Bereg | Hungary | 4400 |
95 | Revita Reumatologiai Rendelo /ID# 202438 | Budapest | Hungary | 1027 | |
96 | CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 205804 | Szekesfehervar | Hungary | 8000 | |
97 | Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 202437 | Veszprem | Hungary | 8200 | |
98 | Malopolskie Centrum Kliniczne /ID# 206473 | Cracow | Malopolskie | Poland | 30-149 |
99 | McBk Sc /Id# 212575 | Grodzisk Mazowiecki | Mazowieckie | Poland | 05-825 |
100 | NBR Polska /ID# 206476 | Warsaw | Mazowieckie | Poland | 00-465 |
101 | ClinicMed Daniluk, Nowak Sp.j. /ID# 212576 | Białystok | Podlaskie | Poland | 15-879 |
102 | Reumatika - Centrum Reumatologii NZOZ /ID# 206472 | Warsaw | Poland | 02-691 | |
103 | GCM Medical Group, PSC /ID# 167983 | San Juan | Puerto Rico | 00909 | |
104 | Hospital Universitario A Coruña - CHUAC /ID# 202140 | A Coruña | A Coruna | Spain | 15006 |
105 | Hospital Unversitario Marques de Valdecilla /ID# 202133 | Santander | Cantabria | Spain | 39008 |
106 | Hospital Regional de Malaga /ID# 202137 | Málaga | Malaga | Spain | 29010 |
107 | Hospital Clinic /ID# 206575 | Barcelona | Spain | 08036 | |
108 | Hospital Santa Creu i Sant Pau /ID# 206535 | Barcelona | Spain | 08041 | |
109 | Hospital Universitario Basurto /ID# 206462 | Bilbao | Spain | 48013 | |
110 | Hospital Universitario Virgen de las Nieves /ID# 209705 | Granada | Spain | 18014 | |
111 | Hospital Clinico Universitario San Carlos /ID# 202135 | Madrid | Spain | 28040 | |
112 | Hospital Universitario y Politecnico La Fe /ID# 202139 | Valencia | Spain | 46026 | |
113 | The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 201976 | Newcastle Upon Tyne | United Kingdom | NE1 4LP | |
114 | University of Oxford /ID# 201974 | Oxford | United Kingdom | OX3 7LF | |
115 | Warrington and Halton Teaching Hosp NHS Foundation Trust /ID# 206002 | Warrington | United Kingdom | WA5 1LZ |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: AbbVie Inc., AbbVie
Study Documents (Full-Text)
More Information
Publications
None provided.- M16-063
- 2018-000666-10
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Period Title: Overall Study | ||||||
STARTED | 19 | 62 | 41 | 39 | 41 | 40 |
COMPLETED | 17 | 58 | 38 | 34 | 35 | 38 |
NOT COMPLETED | 2 | 4 | 3 | 5 | 6 | 2 |
Baseline Characteristics
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo | Total |
---|---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks | Total of all reporting groups |
Overall Participants | 19 | 62 | 41 | 39 | 41 | 40 | 242 |
Age (years) [Mean (Standard Deviation) ] | |||||||
Mean (Standard Deviation) [years] |
57.6
(9.12)
|
56.2
(12.82)
|
59.2
(11.11)
|
59.7
(10.95)
|
58.1
(11.01)
|
57.7
(10.60)
|
58.0
(11.27)
|
Sex: Female, Male (Count of Participants) | |||||||
Female |
17
89.5%
|
48
77.4%
|
36
87.8%
|
35
89.7%
|
33
80.5%
|
35
87.5%
|
204
84.3%
|
Male |
2
10.5%
|
14
22.6%
|
5
12.2%
|
4
10.3%
|
8
19.5%
|
5
12.5%
|
38
15.7%
|
Race/Ethnicity, Customized (Count of Participants) | |||||||
White |
19
100%
|
58
93.5%
|
36
87.8%
|
35
89.7%
|
35
85.4%
|
37
92.5%
|
220
90.9%
|
Black or African American |
0
0%
|
3
4.8%
|
4
9.8%
|
4
10.3%
|
3
7.3%
|
3
7.5%
|
17
7%
|
American Indian or Alaska Native |
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
1
2.4%
|
0
0%
|
2
0.8%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
1
1.6%
|
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
2
0.8%
|
Multiple |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.4%
|
0
0%
|
1
0.4%
|
Outcome Measures
Title | Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 |
---|---|
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, Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 18 | 54 | 35 | 29 | 34 | 37 |
Least Squares Mean (90% Confidence Interval) [units on a scale] |
-1.12
|
-2.56
|
-1.52
|
-1.32
|
-1.33
|
-2.87
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | ELS Placebo/UPA Placebo, UPA 15 mg/ELS 60 mg |
---|---|---|
Comments | Mixed-Effect Model Repeated Measure (MMRM) analysis was conducted, testing the superiority of the combination of upadacitinib 15 mg and elsubrutinib 60 mg compared to placebo at Week 12. Data collected after a participant discontinued study drug was considered as missing. The mixed model included the categorical fixed effects of treatment, visit and treatment-by-visit interaction, prior bDMARD use, and baseline DAS28 (CRP) measurement. | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | t-test, 2 sided | |
Comments | ||
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | -1.44 | |
Confidence Interval |
(2-Sided) 90% -2.03 to -0.85 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.36 |
|
Estimation Comments |
Title | Change From Baseline in Clinical Disease Activity Index (CDAI) |
---|---|
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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 18 | 57 | 38 | 35 | 37 | 37 |
Week 2 |
-6.08
|
-16.00
|
-8.95
|
-7.36
|
-8.38
|
-14.03
|
Week 4 |
-11.60
|
-20.24
|
-11.67
|
-10.10
|
-12.90
|
-20.30
|
Week 8 |
-12.46
|
-24.95
|
-15.07
|
-17.10
|
-14.84
|
-23.72
|
Week 12 |
-14.57
|
-27.00
|
-17.50
|
-16.70
|
-16.51
|
-28.85
|
Title | Change From Baseline in Simplified Disease Activity Index (SDAI) |
---|---|
Description | The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global disease activity assessed by the participant on a visual analogue scale from 0 to 10 (cm), global disease activity assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein (CRP; mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86.with higher scores indicating higher disease activity. A negative change from baseline indicates improvement in disease activity. |
Time Frame | Baseline, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 18 | 57 | 38 | 35 | 37 | 37 |
Week 2 |
-6.17
|
-17.01
|
-8.79
|
-7.42
|
-8.54
|
-15.30
|
Week 4 |
-11.80
|
-21.24
|
-11.46
|
-10.15
|
-12.87
|
-21.59
|
Week 8 |
-12.15
|
-25.96
|
-15.26
|
-17.32
|
-15.21
|
-25.07
|
Week 12 |
-14.44
|
-28.06
|
-18.01
|
-17.12
|
-16.73
|
-29.65
|
Title | Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 |
---|---|
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 | At Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Number (90% Confidence Interval) [percentage of participants] |
10.5
55.3%
|
32.3
52.1%
|
19.5
47.6%
|
7.7
19.7%
|
9.8
23.9%
|
42.5
106.3%
|
Title | Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12 |
---|---|
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 | At Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Number (90% Confidence Interval) [percentage of participants] |
21.1
111.1%
|
41.9
67.6%
|
22.0
53.7%
|
10.3
26.4%
|
14.6
35.6%
|
55.0
137.5%
|
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 CDAI of less than or equal to 10. |
Time Frame | Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Week 2 |
10.5
55.3%
|
16.1
26%
|
9.8
23.9%
|
0
0%
|
2.4
5.9%
|
12.5
31.3%
|
Week 4 |
10.5
55.3%
|
29.0
46.8%
|
12.2
29.8%
|
7.7
19.7%
|
12.2
29.8%
|
22.5
56.3%
|
Week 8 |
5.3
27.9%
|
46.8
75.5%
|
17.1
41.7%
|
20.5
52.6%
|
24.4
59.5%
|
35.0
87.5%
|
Week 12 |
26.3
138.4%
|
37.1
59.8%
|
34.1
83.2%
|
17.9
45.9%
|
17.1
41.7%
|
57.5
143.8%
|
Title | Percentage of Participants Achieving Complete 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 CDAI of less than or equal to 2.8. |
Time Frame | Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Week 2 |
0
0%
|
3.2
5.2%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Week 4 |
0
0%
|
6.5
10.5%
|
2.4
5.9%
|
2.6
6.7%
|
0
0%
|
2.5
6.3%
|
Week 8 |
0
0%
|
12.9
20.8%
|
7.3
17.8%
|
2.6
6.7%
|
2.4
5.9%
|
12.5
31.3%
|
Week 12 |
5.3
27.9%
|
14.5
23.4%
|
7.3
17.8%
|
5.1
13.1%
|
0
0%
|
15.0
37.5%
|
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 were classified as meeting the American College of Rheumatology 20% response (ACR20) criteria: ≥ 20% improvement in 68-tender joint count ≥ 20% improvement in 66-swollen joint count and ≥ 20% improvement in at least 3 of the 5 following parameters: 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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Week 2 |
21.1
111.1%
|
45.2
72.9%
|
24.4
59.5%
|
12.8
32.8%
|
14.6
35.6%
|
52.5
131.3%
|
Week 4 |
42.1
221.6%
|
51.6
83.2%
|
29.3
71.5%
|
23.1
59.2%
|
22.0
53.7%
|
55.0
137.5%
|
Week 8 |
36.8
193.7%
|
64.5
104%
|
39.0
95.1%
|
30.8
79%
|
39.0
95.1%
|
67.5
168.8%
|
Week 12 |
47.4
249.5%
|
64.5
104%
|
41.5
101.2%
|
30.8
79%
|
34.1
83.2%
|
72.5
181.3%
|
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 were classified as meeting the American College of Rheumatology 50% response (ACR50) criteria: ≥ 50% improvement in 68-tender joint count ≥ 50% improvement in 66-swollen joint count and ≥ 50% improvement in at least 3 of the 5 following parameters: 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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Week 2 |
0
0%
|
16.1
26%
|
4.9
12%
|
0
0%
|
0
0%
|
12.5
31.3%
|
Week 4 |
10.5
55.3%
|
19.4
31.3%
|
17.1
41.7%
|
2.6
6.7%
|
4.9
12%
|
30.0
75%
|
Week 8 |
5.3
27.9%
|
41.9
67.6%
|
19.5
47.6%
|
12.8
32.8%
|
7.3
17.8%
|
40.0
100%
|
Week 12 |
21.1
111.1%
|
45.2
72.9%
|
29.3
71.5%
|
12.8
32.8%
|
17.1
41.7%
|
47.5
118.8%
|
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 were classified as meeting the American College of Rheumatology 70% response (ACR70) criteria: ≥ 70% improvement in 68-tender joint count ≥ 70% improvement in 66-swollen joint count and ≥ 70% improvement in at least 3 of the 5 following parameters: 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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Week 2 |
0
0%
|
8.1
13.1%
|
2.4
5.9%
|
0
0%
|
0
0%
|
0
0%
|
Week 4 |
0
0%
|
9.7
15.6%
|
4.9
12%
|
2.6
6.7%
|
0
0%
|
15.0
37.5%
|
Week 8 |
0
0%
|
17.7
28.5%
|
4.9
12%
|
2.6
6.7%
|
0
0%
|
25.0
62.5%
|
Week 12 |
15.8
83.2%
|
25.8
41.6%
|
14.6
35.6%
|
5.1
13.1%
|
9.8
23.9%
|
27.5
68.8%
|
Title | Change From Baseline in Tender Joint Count 68 (TJC68) |
---|---|
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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 61 | 39 | 37 | 40 | 40 |
Week 2 |
-2.47
|
-8.42
|
-3.65
|
-3.86
|
-4.88
|
-8.57
|
Week 4 |
-9.21
|
-11.86
|
-5.16
|
-5.39
|
-8.08
|
-12.76
|
Week 8 |
-8.82
|
-15.44
|
-8.43
|
-10.83
|
-9.08
|
-14.76
|
Week 12 |
-8.47
|
-16.33
|
-9.14
|
-9.33
|
-12.58
|
-17.56
|
Title | Change From Baseline in Swollen Joint Count 66 (SJC66) |
---|---|
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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 61 | 39 | 37 | 40 | 40 |
Week 2 |
-3.12
|
-6.06
|
-3.61
|
-3.30
|
-4.13
|
-6.02
|
Week 4 |
-4.70
|
-7.96
|
-5.11
|
-4.67
|
-6.05
|
-8.81
|
Week 8 |
-4.32
|
-10.28
|
-6.15
|
-8.08
|
-7.58
|
-10.11
|
Week 12 |
-5.58
|
-10.86
|
-6.68
|
-7.85
|
-8.59
|
-11.14
|
Title | Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS]) |
---|---|
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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 59 | 39 | 35 | 40 | 39 |
Week 2 |
-14.97
|
-24.02
|
-10.22
|
-8.78
|
-7.61
|
-15.99
|
Week 4 |
-20.87
|
-28.17
|
-12.95
|
-8.41
|
-9.91
|
-25.58
|
Week 8 |
-16.21
|
-31.86
|
-20.92
|
-11.12
|
-13.90
|
-30.70
|
Week 12 |
-23.37
|
-32.27
|
-19.52
|
-10.46
|
-17.84
|
-38.34
|
Title | Change From Baseline in Patient's Global Assessment of Disease Activity (PGA) |
---|---|
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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 59 | 39 | 35 | 40 | 39 |
Week 2 |
-11.87
|
-23.44
|
-11.16
|
-6.47
|
-5.95
|
-14.76
|
Week 4 |
-20.93
|
-25.97
|
-12.79
|
-7.15
|
-8.73
|
-23.02
|
Week 8 |
-15.14
|
-28.05
|
-17.25
|
-6.27
|
-14.25
|
-26.79
|
Week 12 |
-19.55
|
-30.52
|
-19.47
|
-8.45
|
-16.40
|
-33.53
|
Title | Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA) |
---|---|
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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 18 | 58 | 38 | 35 | 37 | 38 |
Week 2 |
-16.31
|
-22.35
|
-19.01
|
-16.12
|
-11.64
|
-24.71
|
Week 4 |
-25.20
|
-33.54
|
-25.33
|
-19.59
|
-18.31
|
-34.17
|
Week 8 |
-24.47
|
-40.00
|
-30.06
|
-33.93
|
-25.21
|
-41.02
|
Week 12 |
-23.19
|
-46.98
|
-30.15
|
-31.68
|
-24.55
|
-50.89
|
Title | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) |
---|---|
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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 59 | 39 | 35 | 40 | 38 |
Week 2 |
-0.22
|
-0.34
|
-0.13
|
-0.06
|
-0.16
|
-0.22
|
Week 4 |
-0.36
|
-0.39
|
-0.11
|
-0.14
|
-0.21
|
-0.33
|
Week 8 |
-0.24
|
-0.47
|
-0.29
|
-0.15
|
-0.15
|
-0.47
|
Week 12 |
-0.30
|
-0.52
|
-0.31
|
-0.12
|
-0.18
|
-0.54
|
Title | Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) |
---|---|
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 in indicates improvement. |
Time Frame | Baseline, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 61 | 39 | 37 | 40 | 40 |
Week 2 |
-0.51
|
-9.29
|
2.26
|
-0.34
|
-0.72
|
-12.27
|
Week 4 |
1.54
|
-10.08
|
2.71
|
-0.78
|
0.72
|
-12.59
|
Week 8 |
3.23
|
-9.97
|
-1.39
|
-2.58
|
-2.93
|
-13.13
|
Week 12 |
1.45
|
-10.95
|
-4.58
|
-5.78
|
-0.81
|
-7.44
|
Title | Change From Baseline in 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. A negative change from baseline indicates improvement in disease activity. |
Time Frame | Baseline, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 59 | 39 | 35 | 40 | 39 |
Week 2 |
-0.46
|
-1.53
|
-0.63
|
-0.44
|
-0.56
|
-1.43
|
Week 4 |
-0.90
|
-1.96
|
-0.87
|
-0.68
|
-0.82
|
-1.98
|
Week 8 |
-0.78
|
-2.40
|
-1.21
|
-1.24
|
-1.11
|
-2.34
|
Week 12 |
-1.12
|
-2.56
|
-1.52
|
-1.32
|
-1.33
|
-2.87
|
Title | Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR) |
---|---|
Description | The DAS28-ESR is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 100 mm) are included in the DAS28 -ESR score. Scores on the DAS28-ESR range from 0 to 10; higher scores indicate more disease activity. |
Time Frame | Baseline, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 59 | 39 | 34 | 40 | 39 |
Week 2 |
-0.46
|
-1.48
|
-0.52
|
-0.46
|
-0.57
|
-1.32
|
Week 4 |
-0.86
|
-1.93
|
-0.79
|
-0.59
|
-0.92
|
-1.90
|
Week 8 |
-0.80
|
-2.41
|
-1.07
|
-1.15
|
-1.20
|
-2.31
|
Week 12 |
-1.18
|
-2.53
|
-1.41
|
-1.24
|
-1.44
|
-2.88
|
Title | Change From Baseline in Morning Stiffness Severity |
---|---|
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, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, had non-missing baseline values, and at least one post-baseline value. Baseline is defined as the last non-missing value prior to the first dose of study drug. |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 59 | 39 | 35 | 40 | 38 |
Week 2 |
-1.76
|
-2.02
|
-0.91
|
-0.68
|
-0.59
|
-1.84
|
Week 4 |
-1.76
|
-2.71
|
-0.82
|
-0.83
|
-1.08
|
-2.51
|
Week 8 |
-1.67
|
-3.07
|
-1.30
|
-0.97
|
-1.50
|
-3.07
|
Week 12 |
-1.61
|
-3.23
|
-1.27
|
-1.30
|
-1.66
|
-3.36
|
Title | Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) |
---|---|
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. The minimal clinically important difference (MCID) in HAQ-DI is defined as change from Baseline ≤ -0.22 for rheumatoid arthritis. |
Time Frame | Baseline, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Week 2 |
52.6
276.8%
|
51.6
83.2%
|
36.6
89.3%
|
30.8
79%
|
36.6
89.3%
|
52.5
131.3%
|
Week 4 |
68.4
360%
|
54.8
88.4%
|
34.1
83.2%
|
41.0
105.1%
|
53.7
131%
|
45.0
112.5%
|
Week 8 |
52.6
276.8%
|
58.1
93.7%
|
51.2
124.9%
|
51.3
131.5%
|
36.6
89.3%
|
65.0
162.5%
|
Week 12 |
47.4
249.5%
|
58.1
93.7%
|
53.7
131%
|
43.6
111.8%
|
43.9
107.1%
|
55.0
137.5%
|
Title | Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission |
---|---|
Description | The EULAR Boolean-based definition of remission is as follows: at any time point, a participant must satisfy all of the following: tender joint count ≤1, swollen joint count ≤1, C-reactive protein ≤1 mg/dl and Patient Global Assessment (PGA) ≤1 (on a 0-10 scale). |
Time Frame | Baseline, Week 2, Week 4, Week 8, and Week 12 |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set: all randomized participants who received at least 1 dose of randomized study drug, nonresponder imputation was used for missing data |
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo |
---|---|---|---|---|---|---|
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks |
Measure Participants | 19 | 62 | 41 | 39 | 41 | 40 |
Week 2 |
0
0%
|
1.6
2.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Week 4 |
0
0%
|
6.5
10.5%
|
2.4
5.9%
|
0
0%
|
0
0%
|
2.5
6.3%
|
Week 8 |
0
0%
|
6.5
10.5%
|
2.4
5.9%
|
5.1
13.1%
|
0
0%
|
12.5
31.3%
|
Week 12 |
0
0%
|
11.3
18.2%
|
9.8
23.9%
|
2.6
6.7%
|
2.4
5.9%
|
10.0
25%
|
Adverse Events
Time Frame | Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after last study drug administration, up to 16 weeks. In addition, serious adverse events and protocol-related nonserious adverse events were collected from the time the participant signed the study-specific informed consent. | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | TEAEs and SAEs are defined as any AE or SAE with onset or worsening reported by a participant from the time that the first dose of study drug is administered until 30 days have elapsed following discontinuation of study drug. TEAEs were collected whether elicited or spontaneously reported by the participant. | |||||||||||
Arm/Group Title | ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo | ||||||
Arm/Group Description | Placebo capsule for elsubrutinib once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; 60 mg elsubrutinib capsule once a day by mouth for 12 weeks | 60 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 20 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 5 mg elsubrutinib capsule once a day by mouth for 12 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for 12 weeks | 15 mg film-coated upadacitinib tablet once a day by mouth for 12 weeks; placebo capsule for elsubrutinib once a day by mouth for 12 weeks | ||||||
All Cause Mortality |
||||||||||||
ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/19 (0%) | 0/62 (0%) | 0/41 (0%) | 0/39 (0%) | 1/41 (2.4%) | 0/40 (0%) | ||||||
Serious Adverse Events |
||||||||||||
ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/19 (5.3%) | 0/62 (0%) | 0/41 (0%) | 2/39 (5.1%) | 3/41 (7.3%) | 0/40 (0%) | ||||||
Cardiac disorders | ||||||||||||
CARDIAC ARREST | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 1/41 (2.4%) | 1 | 0/40 (0%) | 0 |
CORONARY ARTERY DISEASE | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 1/39 (2.6%) | 1 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Infections and infestations | ||||||||||||
PYELONEPHRITIS | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 1/41 (2.4%) | 1 | 0/40 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||
CLAVICLE FRACTURE | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 1/41 (2.4%) | 1 | 0/40 (0%) | 0 |
RIB FRACTURE | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 1/41 (2.4%) | 1 | 0/40 (0%) | 0 |
ROAD TRAFFIC ACCIDENT | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 1/41 (2.4%) | 1 | 0/40 (0%) | 0 |
Investigations | ||||||||||||
PROSTATIC SPECIFIC ANTIGEN INCREASED | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Nervous system disorders | ||||||||||||
LUMBAR RADICULOPATHY | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 1/39 (2.6%) | 1 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||
ELS Placebo/UPA Placebo | UPA 15 mg/ELS 60 mg | ELS 60 mg/UPA Placebo | ELS 20 mg/UPA Placebo | ELS 5 mg/UPA Placebo | UPA 15 mg/ELS Placebo | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 10/19 (52.6%) | 7/62 (11.3%) | 17/41 (41.5%) | 10/39 (25.6%) | 8/41 (19.5%) | 9/40 (22.5%) | ||||||
Gastrointestinal disorders | ||||||||||||
DIARRHOEA | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 3/41 (7.3%) | 3 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
General disorders | ||||||||||||
PERIPHERAL SWELLING | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 1/41 (2.4%) | 1 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Infections and infestations | ||||||||||||
BRONCHITIS | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 1/41 (2.4%) | 1 | 0/39 (0%) | 0 | 1/41 (2.4%) | 1 | 0/40 (0%) | 0 |
SINUSITIS | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 1/41 (2.4%) | 1 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
TOOTH INFECTION | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 1/39 (2.6%) | 1 | 0/41 (0%) | 0 | 1/40 (2.5%) | 1 |
UPPER RESPIRATORY TRACT INFECTION | 1/19 (5.3%) | 1 | 4/62 (6.5%) | 4 | 2/41 (4.9%) | 2 | 3/39 (7.7%) | 3 | 2/41 (4.9%) | 2 | 2/40 (5%) | 2 |
URINARY TRACT INFECTION | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 4/41 (9.8%) | 5 | 2/39 (5.1%) | 2 | 2/41 (4.9%) | 2 | 3/40 (7.5%) | 4 |
Injury, poisoning and procedural complications | ||||||||||||
ANIMAL BITE | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Investigations | ||||||||||||
ALANINE AMINOTRANSFERASE INCREASED | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 2/40 (5%) | 2 |
BLOOD GLUCOSE INCREASED | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||
VITAMIN D DEFICIENCY | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||
ARTHRALGIA | 1/19 (5.3%) | 1 | 1/62 (1.6%) | 1 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
ARTHRITIS | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 1/41 (2.4%) | 1 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
BONE DEFORMITY | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
PAIN IN EXTREMITY | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
RHEUMATOID ARTHRITIS | 2/19 (10.5%) | 2 | 0/62 (0%) | 0 | 3/41 (7.3%) | 3 | 3/39 (7.7%) | 3 | 3/41 (7.3%) | 3 | 0/40 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
ENDOMETRIAL ADENOCARCINOMA | 1/19 (5.3%) | 1 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||
COUGH | 0/19 (0%) | 0 | 1/62 (1.6%) | 1 | 2/41 (4.9%) | 2 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 2/40 (5%) | 2 |
Skin and subcutaneous tissue disorders | ||||||||||||
ALOPECIA | 0/19 (0%) | 0 | 0/62 (0%) | 0 | 0/41 (0%) | 0 | 2/39 (5.1%) | 2 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
ERYTHEMA | 1/19 (5.3%) | 1 | 1/62 (1.6%) | 1 | 0/41 (0%) | 0 | 0/39 (0%) | 0 | 0/41 (0%) | 0 | 0/40 (0%) | 0 |
Limitations/Caveats
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 |
- M16-063
- 2018-000666-10