A Phase 3 Study to Compare Upadacitinib to Abatacept in Subjects With Rheumatoid Arthritis on Stable Dose of Conventional Synthetic Disease- Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response or Intolerance to Biologic DMARDs
- Conditions
- Rheumatoid Arthritis (RA)
- Interventions
- Registration Number
- NCT03086343
- Lead Sponsor
- AbbVie
- Brief Summary
The study objective of Period 1 was to compare the safety and efficacy of upadacitinib 15 mg once daily (QD) to abatacept on a background of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in biologic disease-modifying antirheumatic drug (bDMARD)-inadequate response or bDMARD-intolerant participants with moderately to severely active RA. The study objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg QD in participants with RA who had completed Period 1.
- Detailed Description
This is a Phase 3 multicenter study with 2 periods. Period 1 was a 24-week, randomized, double-blind, parallel-group, active-controlled period designed to compare the safety and efficacy of upadacitinib 15 mg and abatacept for the treatment of signs and symptoms of participants with moderately to severely active RA who had an inadequate response to or intolerance to bDMARD therapy and were currently on a stable dose of csDMARD(s) and had never received abatacept. Period 2 is an open-label, long-term extension study to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg once a day (QD) in participants with RA who had completed Period 1.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 657
- Diagnosis of rheumatoid arthritis (RA) for ≥ 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA
- Participants have been treated for ≥ 3 months prior to the screening visit with ≥ 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration and have never received abatacept prior to the first dose of study drug
- Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide
- Meets the following criteria: ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits and high-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L at Screening
Main
- Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to upadacitinib, tofacitinib, baricitinib and filgotinib)
- Prior exposure to abatacept
- History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA. Current diagnosis of secondary Sjogren's Syndrome is permitted
- Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug: serum aspartate transaminase > 2 × upper limit of normal (ULN); serum alanine transaminase > 2 × ULN; estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula < 40 mL/minute/1.73 meter (m)^2; total white blood cell count < 2,500/ μL; absolute neutrophil count < 1,500/μL; platelet count < 100,000/μL; absolute lymphocyte count < 800/μL; and hemoglobin < 10 g/dL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Primary Cohort: Abatacept/Upadacitinib 15 mg QD Placebo for upadacitinib Period 1: 500 mg (for body weight \<60 kg); 750 mg (for body weight 60-100 kg); and 1000 mg (for body weight \>100 kg) IV infusion at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20. Period 2: open label upadacitinib 15 mg QD for 192 weeks. Primary Cohort: Upadacitinib 15 mg QD/Upadacitinib 15 mg QD Placebo for abatacept (0.9% Sodium Chloride Injection or Solution for Infusion) Period 1: One 15 mg upadacitinib oral tablet QD for 24 weeks. Period 2: open label upadacitinib 15 mg QD for 192 weeks. 30 mg Cohort: Upadacitinib 30 mg QD/Upadacitinib 30 mg QD Placebo for abatacept (0.9% Sodium Chloride Injection or Solution for Infusion) Period 1: One upadacitinib 30 mg oral tablet QD for 24 weeks. Period 2: open label upadacitinib 30 mg (reduced to 15 mg per Amendment 5) QD for 192 weeks. 30 mg Cohort: Abatacept/Upadacitinib 30 mg QD Placebo for upadacitinib Period 1: 500 mg (for body weight \<60 kg); 750 mg (for body weight 60-100 kg); and 1000 mg (for body weight \>100 kg) IV infusion at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20. Period 2: open label upadacitinib 30 mg (reduced to 15 mg per Amendment 5) QD for 192 weeks. Primary Cohort: Abatacept/Upadacitinib 15 mg QD Abatacept Period 1: 500 mg (for body weight \<60 kg); 750 mg (for body weight 60-100 kg); and 1000 mg (for body weight \>100 kg) IV infusion at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20. Period 2: open label upadacitinib 15 mg QD for 192 weeks. Primary Cohort: Abatacept/Upadacitinib 15 mg QD Upadacitinib Period 1: 500 mg (for body weight \<60 kg); 750 mg (for body weight 60-100 kg); and 1000 mg (for body weight \>100 kg) IV infusion at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20. Period 2: open label upadacitinib 15 mg QD for 192 weeks. 30 mg Cohort: Upadacitinib 30 mg QD/Upadacitinib 30 mg QD Upadacitinib Period 1: One upadacitinib 30 mg oral tablet QD for 24 weeks. Period 2: open label upadacitinib 30 mg (reduced to 15 mg per Amendment 5) QD for 192 weeks. Primary Cohort: Upadacitinib 15 mg QD/Upadacitinib 15 mg QD Upadacitinib Period 1: One 15 mg upadacitinib oral tablet QD for 24 weeks. Period 2: open label upadacitinib 15 mg QD for 192 weeks. 30 mg Cohort: Abatacept/Upadacitinib 30 mg QD Abatacept Period 1: 500 mg (for body weight \<60 kg); 750 mg (for body weight 60-100 kg); and 1000 mg (for body weight \>100 kg) IV infusion at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20. Period 2: open label upadacitinib 30 mg (reduced to 15 mg per Amendment 5) QD for 192 weeks. 30 mg Cohort: Abatacept/Upadacitinib 30 mg QD Upadacitinib Period 1: 500 mg (for body weight \<60 kg); 750 mg (for body weight 60-100 kg); and 1000 mg (for body weight \>100 kg) IV infusion at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 20. Period 2: open label upadacitinib 30 mg (reduced to 15 mg per Amendment 5) QD for 192 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Non-inferiority) Baseline and Week 12 The Disease Activity Score (DAS) 28 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 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
Name Time Method Change From Baseline in Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority) Baseline and Week 12 The Disease Activity Score (DAS) 28 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 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.
Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score (DAS) 28 C-Reactive Protein (CRP) at Week 12 (Superiority) At Week 12 The Disease Activity Score (DAS) 28 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 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS 28 score less than 2.6 indicates clinical remission.
Trial Locations
- Locations (161)
SunValley Arthritis Center, Lt /ID# 154558
🇺🇸Peoria, Arizona, United States
AZ Arthritis & Rheum Research /ID# 156539
🇺🇸Sun City, Arizona, United States
AZ Arth & Rheum Res /ID# 167161
🇺🇸Tucson, Arizona, United States
CHI St. Vincent Medical Group /ID# 154561
🇺🇸Hot Springs, Arkansas, United States
Saint Jude Heritage /ID# 158833
🇺🇸Fullerton, California, United States
Kotha and Kotha /ID# 154573
🇺🇸La Mesa, California, United States
Denver Arthritis Clinic /ID# 159195
🇺🇸Denver, Colorado, United States
Arthritis and Rheum Clin N. CO /ID# 155673
🇺🇸Fort Collins, Colorado, United States
Scientia Medical Research /ID# 159189
🇺🇸Lakewood, Colorado, United States
Clinical Res of West FL, Inc. /ID# 154576
🇺🇸Clearwater, Florida, United States
Scroll for more (151 remaining)SunValley Arthritis Center, Lt /ID# 154558🇺🇸Peoria, Arizona, United States