A Phase 3, Randomized, Double-Blind, Study Comparing Upadacitinib (ABT-494) to Placebo in Subjects With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug (bDMARD)
Overview
- Phase
- Phase 3
- Intervention
- Upadacitinib
- Conditions
- Psoriatic Arthritis
- Sponsor
- AbbVie
- Enrollment
- 642
- Locations
- 165
- Primary Endpoint
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a Phase 3 multicenter study that included two periods. Period 1 was designed to compare the safety, tolerability, and efficacy of upadacitinib 15 mg once daily (QD) and 30 mg QD versus placebo in participants with moderately to severely active Psoriatic Arthritis (PsA) who had an inadequate response to Biological Disease Modifying Anti-Rheumatic Drug (bDMARDs). Period 2 evaluated the safety, tolerability and efficacy of upadacitinib 15 mg QD and 30 mg QD in subjects with PsA who completed Period 1.
Detailed Description
The study included a 35-day screening period; a 56-week blinded period which included 24 weeks of randomized, double-blind, parallel-group, placebo-controlled treatment followed by an additional 32 weeks of treatment blinded to the dose of upadacitinib (Period 1); a long-term extension period of up to a total treatment duration of up to approximately 3 years (Period 2); and a 30-day follow-up call or visit. All participants in Period 1 who were randomized to receive Placebo up to 24 weeks were pooled for the assessment of all outcome measures. All participants receiving upadacitinib 30 mg QD during Period 2 were switched to upadacitinib 15 mg QD following a protocol amendment and were pooled for AE reporting.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Clinical diagnosis of PsA with symptom onset at least 6 months prior to the Screening Visit and fulfillment of the Classification Criteria for PsA (CASPAR) criteria
- •Participant has active disease at Baseline defined as \>= 3 tender joints (based on 68 joint counts) and \>= 3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits
- •Diagnosis of active plaque psoriasis or documented history of plaque psoriasis
- •Participant has had an inadequate response (lack of efficacy after a minimum 12 week duration of therapy) or intolerance to treatment with at least 1 bDMARD.
Exclusion Criteria
- •Prior exposure to any Janus Kinase (JAK) inhibitor (including but not limited to ruxolitinib, tofacitinib, baricitinib, and filgotinib)
- •Current treatment with \> 2 non-biologic DMARDs or use of DMARDs other than Methotrexate (MTX), Sulfasalazine (SSZ), Leflunomide (LEF), apremilast, Hydroxychloroquine (HCQ), bucillamine or iguratimod or use of MTX in combination with LEF at Baseline.
- •History of fibromyalgia, any arthritis with onset prior to age 17 years, or current diagnosis of inflammatory joint disease other than PsA (including, but not limited to rheumatoid arthritis, gout, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, systemic lupus erythematosus). Prior history of reactive arthritis or axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis is permitted if documentation of change in diagnosis to PsA or additional diagnosis of PsA is made. Prior history of fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly.
Arms & Interventions
Upadacitinib 15 mg
Administered once daily.
Intervention: Upadacitinib
Placebo / Upadacitinib 30 mg
Administered once daily.
Intervention: Placebo
Placebo / Upadacitinib 30 mg
Administered once daily.
Intervention: Upadacitinib
Upadacitinib 30 mg
Administered once daily.
Intervention: Upadacitinib
Placebo / Upadacitinib 15 mg
Administered once daily.
Intervention: Placebo
Placebo / Upadacitinib 15 mg
Administered once daily.
Intervention: Upadacitinib
Outcomes
Primary Outcomes
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
Time Frame: Baseline and Week 12
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
Secondary Outcomes
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16(Baseline and Week 16)
- Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24(Week 24)
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2(Baseline and Week 2)
- Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Score at Week 16(Baseline and Week 16)
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16(Baseline and Week 16)
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12(Baseline and Week 12)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12(Baseline and Week 12)