A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously in Subjects With Active Psoriatic Arthritis
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Arthritis, Psoriatic
- Sponsor
- Centocor, Inc.
- Enrollment
- 407
- Primary Endpoint
- American College of Rheumatology (ACR) 20 Response at Week 14
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and efficacy (improvement of signs and symptoms) of subcutaneous (under the skin) injections of golimumab for the treatment of active psoriatic arthritis (PsA). Efficacy will be measured by reduction in the signs and symptoms of active PsA, including effects on joint pain and swelling, changes on x-ray related to joint damage, psoriasis skin lesions, physical function, and quality of life.
Detailed Description
Anti-tumor necrosis factor (TNF) agents have been shown to be effective in improving arthritis and psoriasis symptoms in patients with active psoriatic arthritis. Golimumab is a new anti-TNFa agent. This is a multicenter, randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), placebo-controlled, parallel group study comparing safety and efficacy of golimumab 50mg, golimumab 100mg, and placebo subcutaneous injections administered every 4 weeks, in subjects with active PsA. The total duration of treatment is approximately 5 years. In the first portion of the study, some patients will be randomly assigned to receive placebo treatment through the Week 20 injection; others will be assigned to golimumab 50mg or golimumab 100mg groups through the Week 20 injection. There is an "early escape" at Week 16 in the study whereby patients who meet criteria for minimal improvement in their joints will be switched to golimumab if they were on placebo, or have the golimumab dose increased if they were originally assigned to the golimumab 50mg group. At Week 24, the placebo group subjects will switch to golimumab 50mg injections, and all patients will continue receiving in a blinded manner either 50 or 100mg golimumab injections every 4 weeks until the first 52 weeks of data are fully collected on all the subjects (database lock). After this 52-week database lock, everyone will be unblinded to the golimumab dose, and continue to receive golimumab treatment through Week 252 as part of a long-term extension phase of the study, with options for adjusting concomitant PsA medications and/or increasing the dose of golimumab. The study hypothesis is that golimumab will be more effective than placebo both in terms of reducing the signs and symptoms of PsA, as measured by the American College of Rheumatology (ACR) 20 response at Week 14, and inhibiting the amount of damage due to PsA seen on x-rays of the hand and feet at Week 24, while maintaining an acceptable safety profile. Golimumab 50mg, Golimumab 100mg, or placebo injected under the skin every 4 weeks at Weeks 0, 4, 8, 12, 16, and 20, followed by injections of either Golimumab 50mg or Golimumab 100mg every 4 weeks, for approximately 5 years total duration from the time of the first study agent injection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Psoriatic arthritis (PsA) diagnosed \> 6months prior
- •Active PsA at the time of screening and at baseline visits, with \>= 3 swollen joints and \>= 3 tender joints
- •Have at least 1 of the PsA subsets (DIP joint arthritis, polyarticular arthritis without rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis)
- •Active plaque psoriasis with a lesion \>= 2cm in diameter
- •Active arthritis despite current disease modifying anti-rheumatic drug (DMARD) or nonsteroidal anti-inflammatory drug (NSAID) therapy
- •Stable doses of methotrexate, low-dose corticosteroids, and NSAIDs are permitted.
Exclusion Criteria
- •No prior treatment with biologic anti-TNF agents (infliximab, etanercept, adalimumab)
- •No treatment with alefacept or efalizumab within 3 months prior to the first study drug injection
- •No DMARDs other than methotrexate, or immunosuppressive drugs within 4 weeks prior to the first study drug injection.
Outcomes
Primary Outcomes
American College of Rheumatology (ACR) 20 Response at Week 14
Time Frame: Baseline (Week 0), Week 4, Week 8 and Week 14
ACR 20 response is an improvement of \>= 20% from baseline (baseline measurement is defined as the closest measurement taken prior to or at the time of the initiation of study medication administration) in both the tender and swollen joint count and in at least 3 of the 5 assessments (Patient's assessment of pain, Patient's global assessment of disease activity, Physician's global assessment of disease activity Visual Analogue Scale \[VAS\], Health Assessment Questionnaire \[HAQ\] and C-reactive protein \[CRP\])
Change From Baseline in Total Radiographic Scores of the Hands and Feet at Week 24
Time Frame: Baseline and Week 24
Summary of change from baseline in total van der Heijde-Sharp (vdH-S) score of the hands and feet, as modified for psoriatic arthritis, at Week 24. The vdH-S score is the sum of joint erosion score and joint-space narrowing (JSN) score. The total score ranges from 0 to 528 with higher scores indicating more joint damage. For the change from baseline, positive values show an increase in damage.
Secondary Outcomes
- Improvement From Baseline in Health Assessment Questionnaire Scores at Week 24(Baseline, Week 4, Week 8, Week 14, Week 16, Week 20 and Week 24)
- Change From Baseline in the Physical Component Summary Score of the 36-item Short Form Health Survey at Week 14(Baseline and Week 14)
- American College of Rheumatology 20 at Week 24(Baseline, Week 4, Week 8, Week 14, Week 16, Week 20 and Week 24)
- Psoriasis Area and Severity Index (PASI) 75 Response at Week 14 in a Subset of Patients With ≥ 3 Percent Body Surface Area (BSA) Psoriasis Skin Involvement at Baseline(Baseline, Week 4, Week 8 and Week 14)