A Study of the Safety and Efficacy of Golimumab in Patients With Active Psoriatic Arthritis

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously in Subjects With Active Psoriatic Arthritis

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Biological: golimumab
* Biological: Placebo; golimumab
* Biological: golimumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 002<br>golimumab 50 mg sc injs every 4 wks from wk 0 thru 5 yrs (unless early escape at wk 16); golimumab - if early escape, 100mg sc injection every 4 wks beginning wk 16 up to 5 yrs; golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100mg | Biological: golimumab<br>* 50 mg sc injs every 4 wks from wk 0 thru 5 yrs (unless early escape at wk 16); golimumab - if early escape, 100mg sc injection every 4 wks beginning wk 16 up to 5 yrs; golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100mg<br>|
| Experimental: 001<br>Placebo; golimumab SC injections ever 4 wks thru Wk 20 (unless early escape at wk 16); golimumab - if early escape, 50mg sc injection from wk 16 up to 5 yrs; golimumab -50mg sc injection beginning Wk 24 up to 5 yrs (unless early escape); golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100 mg | Biological: Placebo; golimumab<br>* SC injections ever 4 wks thru Wk 20 (unless early escape at wk 16); golimumab - if early escape, 50mg sc injection from wk 16 up to 5 yrs; golimumab -50mg sc injection beginning Wk 24 up to 5 yrs (unless early escape); golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100 mg<br>|
| Experimental: 003<br>golimumab 100 mg sc injections every 4 wks from wk 0 up to 5 yrs | Biological: golimumab<br>* 100 mg sc injections every 4 wks from wk 0 up to 5 yrs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology (ACR) 20 Response at 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]) | Baseline (Week 0), Week 4, Week 8 and Week 14 | 
| Change From Baseline in Total Radiographic Scores of the Hands and Feet at 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. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Number of patients (randomized patients with >= 3 percent Body Surface Area [BSA] psoriasis skin involvement at baseline) with Psoriasis Area and Severity Index (PASI) 75 response at Week 14. PASI is the widely used tool for the measurement of severity of psoriasis. PASI combines the assessment of the severity of lesions and the area affected into a single score in the range of 0 to 72. Zero (0) means no disease and 72 means maximal disease. PASI 75 Response at Week 14 means reduction in PASI score by 75 percent at Week 14. | Baseline, Week 4, Week 8 and Week 14 | 
| Improvement From Baseline in Health Assessment Questionnaire Scores at Week 24 | Summary of improvement from baseline in Health Assessment Questionnaire (HAQ) score at Week (Wk) 24. This 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area based on the worst score from the questions that pertain to that task. The HAQ score is determined by the average of the 8 scores. | 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 | The short form health survey (SF-36) is a well-validated and widely used quality-of-life instrument employed in numerous disease states. It is a self-administered survey that measures eight domains of health including: physical functioning, role limitations due to physical health (role-physical), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems (role-emotional) and general mental health. Scoring of the SF-36 was based on the SF-36 Manual and Interpretation Guide. Worst value is 0 and best value is 100. | Baseline and Week 14 | 
| American College of Rheumatology 20 at Week 24 | Number of Patients who achieved an American College of Rheumatology (ACR) 20 response at Week (Wk) 24. ACR 20 response is an improvement of >= 20% from baseline 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]) | Baseline, Week 4, Week 8, Week 14, Week 16, Week 20 and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriatic Arthritis, Spondyloarthritis, Spondyloarthropathy, subcutaneous injection