A Study Comparing Upadacitinib (ABT-494) to Placebo in Participants With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Biologic Disease Modifying Anti-Rheumatic Drug
- Registration Number
- NCT03104374
- Lead Sponsor
- AbbVie
- Brief Summary
This is a Phase 3 multicenter study that includes two periods. Period 1 is designed to compare the safety, tolerability, and efficacy of ABT-494 Dose A once daily (QD) and Dose B QD versus placebo in participants with moderately to severely active Psoriatic Arthritis (PsA) who have an inadequate response to Biological Disease Modifying Anti-Rheumatic Drug (bDMARDs). Period 2 evaluates the safety, tolerability and efficacy of ABT-494 Dose A QD and Dose B QD in subjects with PsA who have completed Period 1.
- Detailed Description
The study includes a 35-day screening period, a 56-week blinded period (Period 1), a long-term extension period of up to a total treatment duration of approximately 3 years (Period 2), and a 30-day follow-up call or visit.
Period 1 includes 24 weeks of randomized, double-blind, parallel-group, placebo-controlled treatment followed by an additional 32 weeks of blinded treatment where all participants were to receive upadacitinib; at Week 24 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment.
Participants who meet eligibility criteria will be randomized in a 2:2:1:1 ratio to one of four treatment groups:
* Group 1: Upadacitinib 15 mg
* Group 2: Upadacitinib 30 mg
* Group 3: Placebo for 24 weeks followed by upadacitinib 15 mg
* Group 4: Placebo for 24 weeks followed by upadacitinib 30 mg
Participants who complete the Week 56 visit (end of Period 1) will enter the long-term extension portion of the study, Period 2, and continue study treatment as assigned in Period 1 in a blinded manner until the last participant completes the last visit of Period 1 (Week 56), when study drug assignment in both periods will be unblinded and study drug will be dispensed in an open-label fashion until the completion of Period 2.
At Week 16, rescue therapy will be offered to participants classified as non-responders (defined as not achieving at least 20% improvement in tender joint count (TJC) and/or swollen joint count (SJC) at both Week 12 and Week 16). Starting at Week 36, participants who fail to demonstrate at least 20% improvement in either or both TJC and SJC compared to Baseline at 2 consecutive visits will be discontinued from study drug treatment. Additionally, in participants continuing on study drug, starting at the Week 36 visit, initiation of or change in background PsA medication(s) is allowed as per local label.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 642
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABT-494 Dose A ABT-494 It is administered once daily. Placebo followed by ABT-494 Dose B Placebo It is administered once daily. Placebo followed by ABT-494 Dose B ABT-494 It is administered once daily. ABT-494 Dose B ABT-494 It is administered once daily. Placebo followed by ABT-494 Dose A Placebo It is administered once daily. Placebo followed by ABT-494 Dose A ABT-494 It is administered once daily.
- Primary Outcome Measures
Name Time Method Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 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 Outcome Measures
Name Time Method Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 Baseline and Week 12 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.Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16 Baseline and Week 16 PASI is a composite score based on the percentage of the body surface area (BSA) affected by psoriasis and the intensity of erythema (reddening), induration (thickening or hardening of the skin), and desquamation (peeling of the skin) of lesions assessed at 4 anatomic sites (head, upper extremities, trunk, and lower extremities). At each location, the percentage of BSA involvement is assigned a score from 0 (no involvement) to 6 (90% to 100% involvement), and erythema, induration, and desquamation are scored on a scale from 0 (no symptoms) to 4 (very marked).
The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score.Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 Baseline and Week 12 The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24 Week 24 A participant was classified as achieving MDA if 5 of the following 7 criteria were met:
* Tender joint count (out of 68 joints) ≤ 1
* Swollen joint count (out of 66 joints) ≤ 1
* PASI score ≤ 1 (score ranges from 0 - 72) or percent BSA involved with psoriasis ≤ 3%
* Patient's assessment of pain ≤ 1.5 (NRS from 0 to 10)
* Patient's Global Assessment of disease activity ≤ 2 (NRS from 0 to 10)
* HAQ-DI score ≤ 0.5 (index score ranges from 0 to 3)
* Leeds Enthesitis Index ≤ 1 (assesses the presence or absence of enthesitis at 3 bilateral sites, with an overall score range from 0 to 6)Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2 Baseline and Week 2 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).Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Score at Week 16 Baseline and Week 16 The SAPS is an 11-item self-assessment of psoriasis symptoms that includes questions on: pain, itching, redness, scaling, flaking, bleeding, burning, stinging, tenderness, pain due to skin cracking, and joint pain. Each item is scored from 0 to 10, with 0 being least severe and 10 being most severe. The total score is generated by summing the 11 items and ranges from 0 to 110 (worst). A negative change from Baseline in the total score indicates improvement.
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria:
1. ≥ 50% improvement in 68-tender joint count;
2. ≥ 50% improvement in 66-swollen joint count; and
3. ≥ 50% 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).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 The sIGA is a 5 point scale ranging from 0 to 4, based on the investigator's assessment of the average elevation, erythema, and scaling of all psoriatic lesions at the current visit. A lower score indicates less severe psoriasis (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe).
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 Baseline and Week 12 Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR70 response criteria:
1. ≥ 70% improvement in 68-tender joint count;
2. ≥ 70% improvement in 66-swollen joint count; and
3. ≥ 70% 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).Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 Baseline and Week 12 The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days, including physical fatigue (e.g., I feel tired), functional fatigue (e.g., trouble finishing things), emotional fatigue (e.g., frustration), and social consequences of fatigue (e.g., limits social activity). Participants respond to the questions on a scale from 0 'not at all' to 4 'very much'. The FACIT Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement.
Trial Locations
- Locations (165)
Arizona Arthritis & Rheumatology Research, PLLC /ID# 160047
🇺🇸Mesa, Arizona, United States
Sun Valley Arthritis Center Ltd. /ID# 161203
🇺🇸Peoria, Arizona, United States
Duplicate_AZ Arthritis and Rheumotology Research, PLLC /ID# 160006
🇺🇸Phoenix, Arizona, United States
Osteoporosis Medical Center /ID# 161411
🇺🇸Beverly Hills, California, United States
Triwest Research Associates /ID# 159915
🇺🇸El Cajon, California, United States
Duplicate_Providence Medical Foundation /ID# 160005
🇺🇸Fullerton, California, United States
Care Access Research, Huntington Beach /ID# 160049
🇺🇸Huntington Beach, California, United States
Purushotham & Akther Kotha MD, Inc /ID# 159834
🇺🇸La Mesa, California, United States
Colorado Arthritis Associates /ID# 159856
🇺🇸Lakewood, Colorado, United States
Duplicate_Arthritis & Rheumatic Disease Specialties /ID# 161409
🇺🇸Aventura, Florida, United States
Scroll for more (155 remaining)Arizona Arthritis & Rheumatology Research, PLLC /ID# 160047🇺🇸Mesa, Arizona, United States