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

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: Placebo for elsubrutinib; Drug: Placebo for upadacitinib; Drug: Elsubrutinib; Drug: Upadacitinib

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 Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven /ID# 201927
  • Bruxelles-Capitale
    • Brussels, Bruxelles-Capitale, Belgium, 1070
      • CUB Hospital Erasme /ID# 201965
    • Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium, 1200
      • Cliniques Universitaires Saint Luc /ID# 201756
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • UZ Ghent /ID# 201757
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5M 0H4
      • Rheumatology Research Assoc /ID# 207299
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Manitoba Clinic /ID# 202126
    • Winnipeg, Manitoba, Canada, R3N 0K6
      • CIADS Research Co Ltd /ID# 202125
  • Ontario
    • Mississauga, Ontario, Canada, L5M 2V8
      • Credit Valley Rheumatology /ID# 202124
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hosp.-Toronto /ID# 202652
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 3H3
      • Dr. Latha Naik /ID# 212972
• Czechia
  • Ostrava, Czechia, 702 00
    • Revmatologie MUDr. Klara Sirova /ID# 205185
  • Pardubice, Czechia, 530 02
    • CCR Czech a.s /ID# 202144
  • Jihlava
    • Jihlava 1, Jihlava, Czechia, 586 01
      • Revmatolog s.r.o. /ID# 202610
  • Praha 2
    • Prague 2, Praha 2, Czechia, 128 00
      • Revmatologicky ustav Praha /ID# 202142
• Hungary
  • Budapest, Hungary, 1027
    • Revita Reumatologiai Rendelo /ID# 202438
  • Szekesfehervar, Hungary, 8000
    • CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 205804
  • Veszprem, Hungary, 8200
    • Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 202437
  • Borsod-Abauj-Zemplen
    • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3529
      • CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 202439
  • Szabolcs-Szatmar-Bereg
    • Nyíregyháza, Szabolcs-Szatmar-Bereg, Hungary, 4400
      • Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatokorhaz /ID# 202441
• Poland
  • Warsaw, Poland, 02-691
    • Reumatika - Centrum Reumatologii NZOZ /ID# 206472
  • Malopolskie
    • Cracow, Malopolskie, Poland, 30-149
      • Malopolskie Centrum Kliniczne /ID# 206473
  • Mazowieckie
    • Grodzisk Mazowiecki, Mazowieckie, Poland, 05-825
      • McBk Sc /Id# 212575
    • Warsaw, Mazowieckie, Poland, 00-465
      • NBR Polska /ID# 206476
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-879
      • ClinicMed Daniluk, Nowak Sp.j. /ID# 212576
• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • GCM Medical Group, PSC /ID# 167983
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic /ID# 206575
  • Barcelona, Spain, 08041
    • Hospital Santa Creu i Sant Pau /ID# 206535
  • Bilbao, Spain, 48013
    • Hospital Universitario Basurto /ID# 206462
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves /ID# 209705
  • Madrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos /ID# 202135
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe /ID# 202139
  • A Coruna
    • A Coruña, A Coruna, Spain, 15006
      • Hospital Universitario A Coruña - CHUAC /ID# 202140
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Unversitario Marques de Valdecilla /ID# 202133
  • Malaga
    • Málaga, Malaga, Spain, 29010
      • Hospital Regional de Malaga /ID# 202137
• United Kingdom
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 201976
  • Oxford, United Kingdom, OX3 7LF
    • University of Oxford /ID# 201974
  • Warrington, United Kingdom, WA5 1LZ
    • Warrington and Halton Teaching Hosp NHS Foundation Trust /ID# 206002
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Rheum Assoc of North Alabama /ID# 167382
  • Arizona
    • Mesa, Arizona, United States, 85210
      • AZ Arthritis & Rheum Research /ID# 167446
    • Peoria, Arizona, United States, 85381
      • SunValley Arthritis Center, Lt /ID# 213073
    • Phoenix, Arizona, United States, 85032
      • AZ Arthritis and Rheum Researc /ID# 167448
  • California
    • Fullerton, California, United States, 92835
      • St. Joseph Heritage Healthcare /ID# 167379
    • La Mesa, California, United States, 91942
      • Purushotham, Akther & Roshan K /ID# 168121
    • Los Alamitos, California, United States, 90720
      • Valerius Medical Group /ID# 168123
    • Roseville, California, United States, 95661
      • Sierra Rheumatology /ID# 167976
    • San Diego, California, United States, 92128-2549
      • Rheumatology Center of San Diego /ID# 170690
    • Turlock, California, United States, 95382-2007
      • Iraj Sabahi Research, Inc /ID# 201923
    • Upland, California, United States, 91786
      • Inland Rheum Clin Trials Inc. /ID# 167459
    • Whittier, California, United States, 90606
      • Medvin Clinical Research /ID# 205731
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Rheumatology Consultants of De /ID# 208238
  • Florida
    • Brandon, Florida, United States, 33511
      • Bay Area Arthritis and Osteo /ID# 208111
    • Clearwater, Florida, United States, 33765
      • Clinical Res of West FL, Inc. /ID# 167462
    • DeBary, Florida, United States, 32713-2260
      • Omega Research Maitland, LLC /ID# 167376
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research /ID# 167982
    • Miami, Florida, United States, 33014
      • Lakes Research, LLC /ID# 170660
    • Miami, Florida, United States, 33185-5948
      • Kendall South Medical Center, Inc. /ID# 206857
    • Naples, Florida, United States, 34102
      • Medallion Clinical Research Institute, LLC /ID# 201710
    • Orlando, Florida, United States, 32806
      • Rheum Assoc of Central FL /ID# 170858
    • Orlando, Florida, United States, 32819
      • HMD Research LLC /ID# 208381
    • Ormond Beach, Florida, United States, 32174
      • International Medical Research - Ormond /ID# 170864
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research /ID# 167453
    • Palm Harbor, Florida, United States, 34684
      • Arthritis Center, Inc. /ID# 170695
    • Plantation, Florida, United States, 33324
      • Integral Rheumatology & Immunology Specialists /ID# 206724
    • Saint Petersburg, Florida, United States, 33705
      • BayCare Medical Group /ID# 170860
    • Saint Petersburg, Florida, United States, 33705
      • St. Anthony Comprehensive Rese /ID# 170668
    • Tampa, Florida, United States, 33606-1246
      • Clinical Research of West Florida, Inc /ID# 169099
    • Tampa, Florida, United States, 33613-1244
      • ForCare Clinical Research /ID# 206280
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Clinic /ID# 206279
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Institute of Arthritis Researc /ID# 170694
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials /ID# 167471
    • Skokie, Illinois, United States, 60076
      • Clinical Investigation Specialists - Skokie /ID# 167468
    • Vernon Hills, Illinois, United States, 60061
      • Deerbrook Medical Associates /ID# 207098
  • Kansas
    • Wichita, Kansas, United States, 67205
      • PRN of Kansas /ID# 167985
  • Louisiana
    • Monroe, Louisiana, United States, 71203
      • The Arthritis & Diabetes Clinic, Inc. /ID# 170682
  • Massachusetts
    • Mansfield, Massachusetts, United States, 02048
      • Mansfield Health Center /ID# 167372
    • Worcester, Massachusetts, United States, 01605
      • Advanced Clinical Care /ID# 167367
  • Michigan
    • Lansing, Michigan, United States, 48910
      • June DO, PC /ID# 170670
    • Lansing, Michigan, United States, 48917
      • Beals Instititute /ID# 170658
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39402
      • Arthritis Associates /ID# 209075
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Med Clinics /ID# 167377
  • Missouri
    • Saint Louis, Missouri, United States, 63119-3845
      • Clayton Medical Associates dba Saint Louis Rheumatology /ID# 170650
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC /ID# 200480
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dhmc /Id# 167476
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Ocean Rheumatology /ID# 170673
  • New Mexico
    • Las Cruces, New Mexico, United States, 88011
      • Arthritis and Osteo Assoc /ID# 167443
  • North Carolina
    • Charlotte, North Carolina, United States, 28210-8508
      • DJL Clinical Research, PLLC /ID# 167374
    • Durham, North Carolina, United States, 27704
      • EmergeOrtho, P.A. /ID# 209154
    • Leland, North Carolina, United States, 28451
      • Cape Fear Arthritis Care /ID# 167413
  • Ohio
    • Blue Ash, Ohio, United States, 45242-3763
      • New Horizons Clinical Research /ID# 170862
    • Marietta, Ohio, United States, 45750-1635
      • Marietta Memorial Hospital /ID# 210968
    • Vandalia, Ohio, United States, 45377-9464
      • STAT Research, Inc. /ID# 200485
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103-2400
      • Health Research of Oklahoma /ID# 167370
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Ctr Reading /ID# 170708
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Inst /ID# 167366
    • Nashville, Tennessee, United States, 37203
      • Nashville Arthritis and Rheumatology /ID# 206699
  • Texas
    • Amarillo, Texas, United States, 79124
      • Amarillo Ctr for Clin Research /ID# 200484
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc. /ID# 167475
    • Carrollton, Texas, United States, 75007
      • Trinity Universal Res Assoc /ID# 209252
    • College Station, Texas, United States, 77845
      • Arth and Osteo Clin Brazo Valley /ID# 209401
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research /ID# 167458
    • Houston, Texas, United States, 77004
      • Rheumatic Disease Clin Res Ctr /ID# 167474
    • Houston, Texas, United States, 77065
      • Rheumatology Clinic of Houston /ID# 203689
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research /ID# 207059
    • Lubbock, Texas, United States, 79410-1198
      • West Texas Clinical Research /ID# 205732
    • Mesquite, Texas, United States, 75150
      • SW Rheumatology Res. LLC /ID# 167383
    • Plano, Texas, United States, 75024-5283
      • Trinity Universal Research Association /ID# 209253
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute /ID# 170667
    • San Antonio, Texas, United States, 78229
      • Accurate Clinical Management /ID# 200481
    • Tomball, Texas, United States, 77375
      • DM Clinical Research /ID# 167444
    • Waco, Texas, United States, 76710
      • Arthritis & Osteoporosis Clinic /ID# 167407
  • Virginia
    • Newport News, Virginia, United States, 23606-4434
      • Tidewater Physicians Medical Center /ID# 210884
  • Washington
    • Bothell, Washington, United States, 98021
      • Western Washington Arthritis C /ID# 205821
    • Spokane, Washington, United States, 99204
      • Arthritis Northwest, PLLC /ID# 200479
  • West Virginia
    • Beckley, West Virginia, United States, 25801
      • Rheumatology and Pulmonary cli /ID# 170863
  • Wisconsin
    • Franklin, Wisconsin, United States, 53132
      • Aurora Rheumatology and Immunotherapy Center /ID# 167385

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / 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: Placebo for upadacitinib; Placebo tablet for upadacitinib will be administered orally.; Drug: Elsubrutinib; Elsubrutinib capsule will be administered orally.; Other Names: ABBV-105
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: Placebo for upadacitinib; Placebo tablet for upadacitinib will be administered orally.; Drug: Elsubrutinib; Elsubrutinib capsule will be administered orally.; Other Names: ABBV-105
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: Placebo for upadacitinib; Placebo tablet for upadacitinib will be administered orally.; Drug: Elsubrutinib; Elsubrutinib capsule will be administered orally.; Other Names: ABBV-105
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: Placebo for elsubrutinib; Placebo capsule for elsubrutinib will be administered orally.; Drug: Upadacitinib; Upadacitinib tablet will be administered orally.; Other Names: ABT-494

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) 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. A negative change from baseline indicates improvement in disease activity.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Disease Activity Index (CDAI)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Simplified Disease Activity Index (SDAI)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) 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.	At Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) 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.	At Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria	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.	Week 2, Week 4, Week 8, and Week 12
Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria	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.	Week 2, Week 4, Week 8, and Week 12
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response	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)	Baseline, Week 2, Week 4, Week 8, and Week 12
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response	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)	Baseline, Week 2, Week 4, Week 8, and Week 12
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response	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)	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Tender Joint Count 68 (TJC68)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Swollen Joint Count 66 (SJC66)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS])	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Patient's Global Assessment of Disease Activity (PGA)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Morning Stiffness Severity	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)	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.	Baseline, Week 2, Week 4, Week 8, and Week 12
Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission	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).	Baseline, Week 2, Week 4, Week 8, and Week 12

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2018
• Primary Completion (Actual): March 26, 2020
• Study Completion (Actual): March 26, 2020

Study Registration Dates

• First Submitted: September 21, 2018
• First Submitted That Met QC Criteria: September 21, 2018
• First Posted (Actual): September 25, 2018

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Upadacitinib; ABBV-599; ABBV-105; Elsubrutinib
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: M16-063; 2018-000666-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• 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