Clinical trial NCT03682705: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis (RA)
Keywords: Elsubrutinib
ABBV-105
Upadacitinib
ABBV-599
Rheumatoid Arthritis
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2018-09-25
Enrollment: 242
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months based on the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA
* Participant meets the following minimum disease activity criteria:

  * ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits
  * High-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L (central lab) at Screening Visit
* Participants must have been treated for ≥ 3 months with ≥ 1 biologic disease-modifying anti-rheumatic drug (bDMARD) therapy but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration
* Participants must have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug
* Participants must have discontinued all bDMARDs prior to the first dose of study drug

Exclusion Criteria:

- Participant has prior exposure to any Janus Kinase (JAK) inhibitor for greater than 2 weeks (including but not limited to upadacitinib, tofacitinib, baricitinib, and filgotinib). A washout period of ≥ 30 days is required for any JAK inhibitor prior to the first dose of study drug.

Primary outcomes:
measure: Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in Clinical Disease Activity Index (CDAI)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Simplified Disease Activity Index (SDAI)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
timeFrame: At Week 12
measure: Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) at Week 12
timeFrame: At Week 12
measure: Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria
timeFrame: Week 2, Week 4, Week 8, and Week 12
measure: Percentage of Participants Achieving Complete Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria
timeFrame: Week 2, Week 4, Week 8, and Week 12
measure: Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Tender Joint Count 68 (TJC68)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Swollen Joint Count 66 (SJC66)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Participant's Assessment of Pain (Visual Analog Scale [VAS])
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Patient's Global Assessment of Disease Activity (PGA)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Physician's Global Assessment of Disease Activity (PhGA)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28- ESR)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Change From Baseline in Morning Stiffness Severity
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Percentage of Participants Achieving Minimal Clinically Important Difference (MCID) in Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
measure: Percentage of Participants Achieving American College of Rheumatology/European League Against Rheumatism (EULAR) Boolean Remission
timeFrame: Baseline, Week 2, Week 4, Week 8, and Week 12
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rheum Assoc of North Alabama /ID# 167382
state: Alabama
city: Mesa
country: United States
facility: AZ Arthritis & Rheum Research /ID# 167446
state: Arizona
city: Peoria
country: United States
facility: SunValley Arthritis Center, Lt /ID# 213073
state: Arizona
city: Phoenix
country: United States
facility: AZ Arthritis and Rheum Researc /ID# 167448
state: Arizona
city: Fullerton
country: United States
facility: St. Joseph Heritage Healthcare /ID# 167379
state: California
city: La Mesa
country: United States
facility: Purushotham, Akther & Roshan K /ID# 168121
state: California
city: Los Alamitos
country: United States
facility: Valerius Medical Group /ID# 168123
state: California
city: Roseville
country: United States
facility: Sierra Rheumatology /ID# 167976
state: California
city: San Diego
country: United States
facility: Rheumatology Center of San Diego /ID# 170690
state: California
city: Turlock
country: United States
facility: Iraj Sabahi Research, Inc /ID# 201923
state: California
city: Upland
country: United States
facility: Inland Rheum Clin Trials Inc. /ID# 167459
state: California
city: Whittier
country: United States
facility: Medvin Clinical Research /ID# 205731
state: California
city: Lewes
country: United States
facility: Rheumatology Consultants of De /ID# 208238
state: Delaware
city: Brandon
country: United States
facility: Bay Area Arthritis and Osteo /ID# 208111
state: Florida
city: Clearwater
country: United States
facility: Clinical Res of West FL, Inc. /ID# 167462
state: Florida
city: DeBary
country: United States
facility: Omega Research Maitland, LLC /ID# 167376
state: Florida
city: Edgewater
country: United States
facility: Riverside Clinical Research /ID# 167982
state: Florida
city: Miami
country: United States
facility: Lakes Research, LLC /ID# 170660
state: Florida
city: Miami
country: United States
facility: Kendall South Medical Center, Inc. /ID# 206857
state: Florida
city: Naples
country: United States
facility: Medallion Clinical Research Institute, LLC /ID# 201710
state: Florida
city: Orlando
country: United States
facility: Rheum Assoc of Central FL /ID# 170858
state: Florida
city: Orlando
country: United States
facility: HMD Research LLC /ID# 208381
state: Florida
city: Ormond Beach
country: United States
facility: International Medical Research - Ormond /ID# 170864
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research /ID# 167453
state: Florida
city: Palm Harbor
country: United States
facility: Arthritis Center, Inc. /ID# 170695
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology & Immunology Specialists /ID# 206724
state: Florida
city: Saint Petersburg
country: United States
facility: BayCare Medical Group /ID# 170860
state: Florida
city: Saint Petersburg
country: United States
facility: St. Anthony Comprehensive Rese /ID# 170668
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc /ID# 169099
state: Florida
city: Tampa
country: United States
facility: ForCare Clinical Research /ID# 206280
state: Florida
city: Zephyrhills
country: United States
facility: Florida Medical Clinic /ID# 206279
state: Florida
city: Idaho Falls
country: United States
facility: Institute of Arthritis Researc /ID# 170694
state: Idaho
city: Chicago
country: United States
facility: Great Lakes Clinical Trials /ID# 167471
state: Illinois
city: Skokie
country: United States
facility: Clinical Investigation Specialists - Skokie /ID# 167468
state: Illinois
city: Vernon Hills
country: United States
facility: Deerbrook Medical Associates /ID# 207098
state: Illinois
city: Wichita
country: United States
facility: PRN of Kansas /ID# 167985
state: Kansas
city: Monroe
country: United States
facility: The Arthritis & Diabetes Clinic, Inc. /ID# 170682
state: Louisiana
city: Mansfield
country: United States
facility: Mansfield Health Center /ID# 167372
state: Massachusetts
city: Worcester
country: United States
facility: Advanced Clinical Care /ID# 167367
state: Massachusetts
city: Lansing
country: United States
facility: June DO, PC /ID# 170670
state: Michigan
city: Lansing
country: United States
facility: Beals Instititute /ID# 170658
state: Michigan
city: Hattiesburg
country: United States
facility: Arthritis Associates /ID# 209075
state: Mississippi
city: Tupelo
country: United States
facility: North Mississippi Med Clinics /ID# 167377
state: Mississippi
city: Saint Louis
country: United States
facility: Clayton Medical Associates dba Saint Louis Rheumatology /ID# 170650
state: Missouri
city: Lincoln
country: United States
facility: Physician Research Collaboration, LLC /ID# 200480
state: Nebraska
city: Lebanon
country: United States
facility: Dhmc /Id# 167476
state: New Hampshire
city: Toms River
country: United States
facility: Ocean Rheumatology /ID# 170673
state: New Jersey
city: Las Cruces
country: United States
facility: Arthritis and Osteo Assoc /ID# 167443
state: New Mexico
city: Charlotte
country: United States
facility: DJL Clinical Research, PLLC /ID# 167374
state: North Carolina
city: Durham
country: United States
facility: EmergeOrtho, P.A. /ID# 209154
state: North Carolina
city: Leland
country: United States
facility: Cape Fear Arthritis Care /ID# 167413
state: North Carolina
city: Blue Ash
country: United States
facility: New Horizons Clinical Research /ID# 170862
state: Ohio
city: Marietta
country: United States
facility: Marietta Memorial Hospital /ID# 210968
state: Ohio
city: Vandalia
country: United States
facility: STAT Research, Inc. /ID# 200485
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma /ID# 167370
state: Oklahoma
city: Wyomissing
country: United States
facility: Clinical Research Ctr Reading /ID# 170708
state: Pennsylvania
city: Jackson
country: United States
facility: West Tennessee Research Inst /ID# 167366
state: Tennessee
city: Nashville
country: United States
facility: Nashville Arthritis and Rheumatology /ID# 206699
state: Tennessee
city: Amarillo
country: United States
facility: Amarillo Ctr for Clin Research /ID# 200484
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc. /ID# 167475
state: Texas
city: Carrollton
country: United States
facility: Trinity Universal Res Assoc /ID# 209252
state: Texas
city: College Station
country: United States
facility: Arth and Osteo Clin Brazo Valley /ID# 209401
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research /ID# 167458
state: Texas
city: Houston
country: United States
facility: Rheumatic Disease Clin Res Ctr /ID# 167474
state: Texas
city: Houston
country: United States
facility: Rheumatology Clinic of Houston /ID# 203689
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research /ID# 207059
state: Texas
city: Lubbock
country: United States
facility: West Texas Clinical Research /ID# 205732
state: Texas
city: Mesquite
country: United States
facility: SW Rheumatology Res. LLC /ID# 167383
state: Texas
city: Plano
country: United States
facility: Trinity Universal Research Association /ID# 209253
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute /ID# 170667
state: Texas
city: San Antonio
country: United States
facility: Accurate Clinical Management /ID# 200481
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research /ID# 167444
state: Texas
city: Waco
country: United States
facility: Arthritis & Osteoporosis Clinic /ID# 167407
state: Texas
city: Newport News
country: United States
facility: Tidewater Physicians Medical Center /ID# 210884
state: Virginia
city: Bothell
country: United States
facility: Western Washington Arthritis C /ID# 205821
state: Washington
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC /ID# 200479
state: Washington
city: Beckley
country: United States
facility: Rheumatology and Pulmonary cli /ID# 170863
state: West Virginia
city: Franklin
country: United States
facility: Aurora Rheumatology and Immunotherapy Center /ID# 167385
state: Wisconsin
city: Brussels
country: Belgium
facility: CUB Hospital Erasme /ID# 201965
state: Bruxelles-Capitale
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint Luc /ID# 201756
state: Bruxelles-Capitale
city: Ghent
country: Belgium
facility: UZ Ghent /ID# 201757
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 201927
city: Edmonton
country: Canada
facility: Rheumatology Research Assoc /ID# 207299
state: Alberta
city: Winnipeg
country: Canada
facility: Manitoba Clinic /ID# 202126
state: Manitoba
city: Winnipeg
country: Canada
facility: CIADS Research Co Ltd /ID# 202125
state: Manitoba
city: Mississauga
country: Canada
facility: Credit Valley Rheumatology /ID# 202124
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hosp.-Toronto /ID# 202652
state: Ontario
city: Saskatoon
country: Canada
facility: Dr. Latha Naik /ID# 212972
state: Saskatchewan
city: Jihlava 1
country: Czechia
facility: Revmatolog s.r.o. /ID# 202610
state: Jihlava
city: Prague 2
country: Czechia
facility: Revmatologicky ustav Praha /ID# 202142
state: Praha 2
city: Ostrava
country: Czechia
facility: Revmatologie MUDr. Klara Sirova /ID# 205185
city: Pardubice
country: Czechia
facility: CCR Czech a.s /ID# 202144
city: Miskolc
country: Hungary
facility: CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 202439
state: Borsod-Abauj-Zemplen
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatokorhaz /ID# 202441
state: Szabolcs-Szatmar-Bereg
city: Budapest
country: Hungary
facility: Revita Reumatologiai Rendelo /ID# 202438
city: Szekesfehervar
country: Hungary
facility: CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 205804
city: Veszprem
country: Hungary
facility: Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 202437
city: Cracow
country: Poland
facility: Malopolskie Centrum Kliniczne /ID# 206473
state: Malopolskie
city: Grodzisk Mazowiecki
country: Poland
facility: McBk Sc /Id# 212575
state: Mazowieckie
city: Warsaw
country: Poland
facility: NBR Polska /ID# 206476
state: Mazowieckie
city: Białystok
country: Poland
facility: ClinicMed Daniluk, Nowak Sp.j. /ID# 212576
state: Podlaskie
city: Warsaw
country: Poland
facility: Reumatika - Centrum Reumatologii NZOZ /ID# 206472
city: San Juan
country: Puerto Rico
facility: GCM Medical Group, PSC /ID# 167983
city: A Coruña
country: Spain
facility: Hospital Universitario A Coruña - CHUAC /ID# 202140
state: A Coruna
city: Santander
country: Spain
facility: Hospital Unversitario Marques de Valdecilla /ID# 202133
state: Cantabria
city: Málaga
country: Spain
facility: Hospital Regional de Malaga /ID# 202137
state: Malaga
city: Barcelona
country: Spain
facility: Hospital Clinic /ID# 206575
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau /ID# 206535
city: Bilbao
country: Spain
facility: Hospital Universitario Basurto /ID# 206462
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves /ID# 209705
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos /ID# 202135
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 202139
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust /ID# 201976
city: Oxford
country: United Kingdom
facility: University of Oxford /ID# 201974
city: Warrington
country: United Kingdom
facility: Warrington and Halton Teaching Hosp NHS Foundation Trust /ID# 206002
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: