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

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT03682705
Collaborator
(none)
242
115
6
17.6
2.1
0.1

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

Study Type:
Interventional
Actual Enrollment :
242 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Rheumatoid Arthritis: A Phase 2 Study to Investigate the Safety and Efficacy of ABBV-105 Given Alone or in Combination With Upadacitinib (ABBV-599 Combination) With a Background of Conventional Synthetic DMARDs in Subjects With Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs
Actual Study Start Date :
Oct 8, 2018
Actual Primary Completion Date :
Mar 26, 2020
Actual Study Completion Date :
Mar 26, 2020

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:
  • ABBV-105
  • Drug: Upadacitinib
    Upadacitinib tablet will be administered orally.
    Other Names:
  • ABT-494
  • 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:
  • ABBV-105
  • 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:
  • ABBV-105
  • 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:
  • ABBV-105
  • 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:
  • ABT-494
  • Drug: Placebo for elsubrutinib
    Placebo capsule for elsubrutinib will be administered orally.

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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)

    8. 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)

    9. 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)

    10. 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.

    11. 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.

    12. 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.

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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.

    20. 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.

    21. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT03682705
    Other Study ID Numbers:
    • M16-063
    • 2018-000666-10
    First Posted:
    Sep 25, 2018
    Last Update Posted:
    May 3, 2021
    Last Verified:
    Apr 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.:
    No
    Keywords provided by AbbVie
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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%
    5. Secondary Outcome
    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%
    6. Secondary Outcome
    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%
    7. Secondary Outcome
    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%
    8. Secondary Outcome
    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%
    9. Secondary Outcome
    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%
    10. Secondary Outcome
    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%
    11. Secondary Outcome
    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
    12. Secondary Outcome
    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
    13. Secondary Outcome
    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
    14. Secondary Outcome
    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
    15. Secondary Outcome
    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
    16. Secondary Outcome
    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
    17. Secondary Outcome
    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
    18. Secondary Outcome
    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
    19. Secondary Outcome
    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
    20. Secondary Outcome
    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
    21. Secondary Outcome
    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%
    22. Secondary Outcome
    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

    [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
    Email abbvieclinicaltrials@abbvie.com
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT03682705
    Other Study ID Numbers:
    • M16-063
    • 2018-000666-10
    First Posted:
    Sep 25, 2018
    Last Update Posted:
    May 3, 2021
    Last Verified:
    Apr 1, 2021