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
2 other identifiers
interventional
242
9 countries
115
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2018
Shorter than P25 for phase_2
115 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 21, 2018
CompletedFirst Posted
Study publicly available on registry
September 25, 2018
CompletedStudy Start
First participant enrolled
October 8, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 26, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 26, 2020
CompletedResults Posted
Study results publicly available
May 3, 2021
CompletedMay 3, 2021
April 1, 2021
1.5 years
September 21, 2018
March 4, 2021
April 6, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (21)
Change From Baseline in Clinical Disease Activity Index (CDAI)
Baseline, Week 2, Week 4, Week 8, and Week 12
Change From Baseline in Simplified Disease Activity Index (SDAI)
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
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
At Week 12
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
- +16 more secondary outcomes
Study Arms (6)
ELS placebo/UPA placebo
PLACEBO COMPARATORPlacebo 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
UPA 15 mg/ELS 60 mg
EXPERIMENTAL15 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
ELS 60 mg/UPA placebo
EXPERIMENTAL60 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
ELS 20 mg/UPA placebo
EXPERIMENTAL20 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
ELS 5 mg/UPA placebo
EXPERIMENTAL5 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
UPA 15 mg/ELS placebo
EXPERIMENTAL15 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
Interventions
Elsubrutinib capsule will be administered orally.
Upadacitinib tablet will be administered orally.
Placebo capsule for elsubrutinib will be administered orally.
Placebo tablet for upadacitinib will be administered orally.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- \- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AbbVielead
Study Sites (115)
Rheum Assoc of North Alabama /ID# 167382
Huntsville, Alabama, 35801, United States
AZ Arthritis & Rheum Research /ID# 167446
Mesa, Arizona, 85210, United States
SunValley Arthritis Center, Lt /ID# 213073
Peoria, Arizona, 85381, United States
AZ Arthritis and Rheum Researc /ID# 167448
Phoenix, Arizona, 85032, United States
St. Joseph Heritage Healthcare /ID# 167379
Fullerton, California, 92835, United States
Purushotham, Akther & Roshan K /ID# 168121
La Mesa, California, 91942, United States
Valerius Medical Group /ID# 168123
Los Alamitos, California, 90720, United States
Sierra Rheumatology /ID# 167976
Roseville, California, 95661, United States
Rheumatology Center of San Diego /ID# 170690
San Diego, California, 92128-2549, United States
Iraj Sabahi Research, Inc /ID# 201923
Turlock, California, 95382-2007, United States
Inland Rheum Clin Trials Inc. /ID# 167459
Upland, California, 91786, United States
Medvin Clinical Research /ID# 205731
Whittier, California, 90606, United States
Rheumatology Consultants of De /ID# 208238
Lewes, Delaware, 19958, United States
Bay Area Arthritis and Osteo /ID# 208111
Brandon, Florida, 33511, United States
Clinical Res of West FL, Inc. /ID# 167462
Clearwater, Florida, 33765, United States
Omega Research Maitland, LLC /ID# 167376
DeBary, Florida, 32713-2260, United States
Riverside Clinical Research /ID# 167982
Edgewater, Florida, 32132, United States
Lakes Research, LLC /ID# 170660
Miami, Florida, 33014, United States
Kendall South Medical Center, Inc. /ID# 206857
Miami, Florida, 33185-5948, United States
Medallion Clinical Research Institute, LLC /ID# 201710
Naples, Florida, 34102, United States
Rheum Assoc of Central FL /ID# 170858
Orlando, Florida, 32806, United States
HMD Research LLC /ID# 208381
Orlando, Florida, 32819, United States
International Medical Research - Ormond /ID# 170864
Ormond Beach, Florida, 32174, United States
Millennium Research /ID# 167453
Ormond Beach, Florida, 32174, United States
Arthritis Center, Inc. /ID# 170695
Palm Harbor, Florida, 34684, United States
Integral Rheumatology & Immunology Specialists /ID# 206724
Plantation, Florida, 33324, United States
BayCare Medical Group /ID# 170860
St. Petersburg, Florida, 33705, United States
St. Anthony Comprehensive Rese /ID# 170668
St. Petersburg, Florida, 33705, United States
Clinical Research of West Florida, Inc /ID# 169099
Tampa, Florida, 33606-1246, United States
ForCare Clinical Research /ID# 206280
Tampa, Florida, 33613-1244, United States
Florida Medical Clinic /ID# 206279
Zephyrhills, Florida, 33542, United States
Institute of Arthritis Researc /ID# 170694
Idaho Falls, Idaho, 83404, United States
Great Lakes Clinical Trials /ID# 167471
Chicago, Illinois, 60640, United States
Clinical Investigation Specialists - Skokie /ID# 167468
Skokie, Illinois, 60076, United States
Deerbrook Medical Associates /ID# 207098
Vernon Hills, Illinois, 60061, United States
PRN of Kansas /ID# 167985
Wichita, Kansas, 67205, United States
The Arthritis & Diabetes Clinic, Inc. /ID# 170682
Monroe, Louisiana, 71203, United States
Mansfield Health Center /ID# 167372
Mansfield, Massachusetts, 02048, United States
Advanced Clinical Care /ID# 167367
Worcester, Massachusetts, 01605, United States
June DO, PC /ID# 170670
Lansing, Michigan, 48910, United States
Beals Instititute /ID# 170658
Lansing, Michigan, 48917, United States
Arthritis Associates /ID# 209075
Hattiesburg, Mississippi, 39402, United States
North Mississippi Med Clinics /ID# 167377
Tupelo, Mississippi, 38801, United States
Clayton Medical Associates dba Saint Louis Rheumatology /ID# 170650
St Louis, Missouri, 63119-3845, United States
Physician Research Collaboration, LLC /ID# 200480
Lincoln, Nebraska, 68516, United States
Dhmc /Id# 167476
Lebanon, New Hampshire, 03756, United States
Ocean Rheumatology /ID# 170673
Toms River, New Jersey, 08755, United States
Arthritis and Osteo Assoc /ID# 167443
Las Cruces, New Mexico, 88011, United States
DJL Clinical Research, PLLC /ID# 167374
Charlotte, North Carolina, 28210-8508, United States
EmergeOrtho, P.A. /ID# 209154
Durham, North Carolina, 27704, United States
Cape Fear Arthritis Care /ID# 167413
Leland, North Carolina, 28451, United States
New Horizons Clinical Research /ID# 170862
Blue Ash, Ohio, 45242-3763, United States
Marietta Memorial Hospital /ID# 210968
Marietta, Ohio, 45750-1635, United States
STAT Research, Inc. /ID# 200485
Vandalia, Ohio, 45377-9464, United States
Health Research of Oklahoma /ID# 167370
Oklahoma City, Oklahoma, 73103-2400, United States
Clinical Research Ctr Reading /ID# 170708
Wyomissing, Pennsylvania, 19610, United States
West Tennessee Research Inst /ID# 167366
Jackson, Tennessee, 38305, United States
Nashville Arthritis and Rheumatology /ID# 206699
Nashville, Tennessee, 37203, United States
Amarillo Ctr for Clin Research /ID# 200484
Amarillo, Texas, 79124, United States
Tekton Research, Inc. /ID# 167475
Austin, Texas, 78745, United States
Trinity Universal Res Assoc /ID# 209252
Carrollton, Texas, 75007, United States
Arth and Osteo Clin Brazo Valley /ID# 209401
College Station, Texas, 77845, United States
Metroplex Clinical Research /ID# 167458
Dallas, Texas, 75231, United States
Rheumatic Disease Clin Res Ctr /ID# 167474
Houston, Texas, 77004, United States
Rheumatology Clinic of Houston /ID# 203689
Houston, Texas, 77065, United States
Accurate Clinical Research /ID# 207059
Houston, Texas, 77089, United States
West Texas Clinical Research /ID# 205732
Lubbock, Texas, 79410-1198, United States
SW Rheumatology Res. LLC /ID# 167383
Mesquite, Texas, 75150, United States
Trinity Universal Research Association /ID# 209253
Plano, Texas, 75024-5283, United States
Sun Research Institute /ID# 170667
San Antonio, Texas, 78215, United States
Accurate Clinical Management /ID# 200481
San Antonio, Texas, 78229, United States
DM Clinical Research /ID# 167444
Tomball, Texas, 77375, United States
Arthritis & Osteoporosis Clinic /ID# 167407
Waco, Texas, 76710, United States
Tidewater Physicians Medical Center /ID# 210884
Newport News, Virginia, 23606-4434, United States
Western Washington Arthritis C /ID# 205821
Bothell, Washington, 98021, United States
Arthritis Northwest, PLLC /ID# 200479
Spokane, Washington, 99204, United States
Rheumatology and Pulmonary cli /ID# 170863
Beckley, West Virginia, 25801, United States
Aurora Rheumatology and Immunotherapy Center /ID# 167385
Franklin, Wisconsin, 53132, United States
CUB Hospital Erasme /ID# 201965
Brussels, Brussels Capital, 1070, Belgium
Cliniques Universitaires Saint Luc /ID# 201756
Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium
UZ Ghent /ID# 201757
Ghent, Oost-Vlaanderen, 9000, Belgium
UZ Leuven /ID# 201927
Leuven, 3000, Belgium
Rheumatology Research Assoc /ID# 207299
Edmonton, Alberta, T5M 0H4, Canada
Manitoba Clinic /ID# 202126
Winnipeg, Manitoba, R3A 1M3, Canada
CIADS Research Co Ltd /ID# 202125
Winnipeg, Manitoba, R3N 0K6, Canada
Credit Valley Rheumatology /ID# 202124
Mississauga, Ontario, L5M 2V8, Canada
Mount Sinai Hosp.-Toronto /ID# 202652
Toronto, Ontario, M5G 1X5, Canada
Dr. Latha Naik /ID# 212972
Saskatoon, Saskatchewan, S7K 3H3, Canada
Revmatolog s.r.o. /ID# 202610
Jihlava, Jihlava, 586 01, Czechia
Revmatologicky ustav Praha /ID# 202142
Prague, Praha 2, 128 00, Czechia
Revmatologie MUDr. Klara Sirova /ID# 205185
Ostrava, 702 00, Czechia
CCR Czech a.s /ID# 202144
Pardubice, 530 02, Czechia
CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 202439
Miskolc, Borsod-Abauj Zemplen county, 3529, Hungary
Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatokorhaz /ID# 202441
Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary
Revita Reumatologiai Rendelo /ID# 202438
Budapest, 1027, Hungary
CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 205804
Székesfehérvár, 8000, Hungary
Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 202437
Veszprém, 8200, Hungary
Malopolskie Centrum Kliniczne /ID# 206473
Krakow, Lesser Poland Voivodeship, 30-149, Poland
McBk Sc /Id# 212575
Grodzisk Mazowiecki, Masovian Voivodeship, 05-825, Poland
NBR Polska /ID# 206476
Warsaw, Masovian Voivodeship, 00-465, Poland
ClinicMed Daniluk, Nowak Sp.j. /ID# 212576
Bialystok, Podlaskie Voivodeship, 15-879, Poland
Reumatika - Centrum Reumatologii NZOZ /ID# 206472
Warsaw, 02-691, Poland
GCM Medical Group, PSC /ID# 167983
San Juan, 00909, Puerto Rico
Hospital Universitario A Coruña - CHUAC /ID# 202140
A Coruña, A Coruna, 15006, Spain
Hospital Unversitario Marques de Valdecilla /ID# 202133
Santander, Cantabria, 39008, Spain
Hospital Regional de Malaga /ID# 202137
Málaga, Malaga, 29010, Spain
Hospital Clinic /ID# 206575
Barcelona, 08036, Spain
Hospital Santa Creu i Sant Pau /ID# 206535
Barcelona, 08041, Spain
Hospital Universitario Basurto /ID# 206462
Bilbao, 48013, Spain
Hospital Universitario Virgen de las Nieves /ID# 209705
Granada, 18014, Spain
Hospital Clinico Universitario San Carlos /ID# 202135
Madrid, 28040, Spain
Hospital Universitario y Politecnico La Fe /ID# 202139
Valencia, 46026, Spain
The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 201976
Newcastle upon Tyne, NE1 4LP, United Kingdom
University of Oxford /ID# 201974
Oxford, OX3 7LF, United Kingdom
Warrington and Halton Teaching Hosp NHS Foundation Trust /ID# 206002
Warrington, WA5 1LZ, United Kingdom
Related Publications (1)
Fleischmann R, Friedman A, Drescher E, Singhal A, Cortes-Maisonet G, Doan T, Lu W, Wang Z, Nader A, Housley W, Cohen S, Taylor PC, Blanco R. Safety and efficacy of elsubrutinib or upadacitinib alone or in combination (ABBV-599) in patients with rheumatoid arthritis and inadequate response or intolerance to biological therapies: a multicentre, double-blind, randomised, controlled, phase 2 trial. Lancet Rheumatol. 2022 Jun;4(6):e395-e406. doi: 10.1016/S2665-9913(22)00092-3. Epub 2022 Apr 27.
PMID: 38293957DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Medical Services
- Organization
- AbbVie
Study Officials
- STUDY DIRECTOR
AbbVie Inc.
AbbVie
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 21, 2018
First Posted
September 25, 2018
Study Start
October 8, 2018
Primary Completion
March 26, 2020
Study Completion
March 26, 2020
Last Updated
May 3, 2021
Results First Posted
May 3, 2021
Record last verified: 2021-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
- 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.
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.