Clinical trial NCT00265096: A Study of the Safety and Efficacy of Golimumab in Patients With Active Psoriatic Arthritis
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously in Subjects With Active Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Psoriatic
Keywords: Psoriatic Arthritis
Spondyloarthritis
Spondyloarthropathy
subcutaneous injection
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2005-12-14
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: American College of Rheumatology (ACR) 20 Response at Week 14
timeFrame: Baseline (Week 0), Week 4, Week 8 and Week 14
measure: Change From Baseline in Total Radiographic Scores of the Hands and Feet at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: 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
timeFrame: Baseline, Week 4, Week 8 and Week 14
measure: Improvement From Baseline in Health Assessment Questionnaire Scores at Week 24
timeFrame: Baseline, Week 4, Week 8, Week 14, Week 16, Week 20 and Week 24
measure: Change From Baseline in the Physical Component Summary Score of the 36-item Short Form Health Survey at Week 14
timeFrame: Baseline and Week 14
measure: American College of Rheumatology 20 at Week 24
timeFrame: Baseline, Week 4, Week 8, Week 14, Week 16, Week 20 and Week 24
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: La Jolla
country: United States
state: California
city: Upland
country: United States
state: California
city: Aventura
country: United States
state: Florida
city: Coeur D'Alene
country: United States
state: Idaho
city: Kansas City
country: United States
state: Kansas
city: Wheaton
country: United States
state: Maryland
city: Worcester
country: United States
state: Massachusetts
city: Omaha
country: United States
state: Nebraska
city: Cincinnati
country: United States
state: Ohio
city: Mayfield
country: United States
state: Ohio
city: Lake Oswego
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Duncansville
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Edmonds
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Brussel
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Merksem
country: Belgium
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: North Bay
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Waterloo
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Sainte Foy
country: Canada
state: Quebec
city: Sante Foy
country: Canada
state: Quebec
city: Claire
country: Canada
city: Hamilton Ontario
country: Canada
city: Newmarket
country: Canada
city: Saskatoon
country: Canada
city: Vancouver
country: Canada
city: Bialystok
country: Poland
city: Elblag
country: Poland
city: Kalisz
country: Poland
city: Poznan N/A
country: Poland
city: Szczecin
country: Poland
city: Torun
country: Poland
city: Warsaw
country: Poland
city: Warszawa N/A
country: Poland
city: Santiago De Compostela
country: Spain
city: Valencia
country: Spain
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Middlesbrough
country: United Kingdom
city: Wigan
country: United Kingdom
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Leu JH, Adedokun OJ, Gargano C, Hsia EC, Xu Z, Shankar G. Immunogenicity of golimumab and its clinical relevance in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Rheumatology (Oxford). 2019 Mar 1;58(3):441-446. doi: 10.1093/rheumatology/key309.
citation: Kay J, Fleischmann R, Keystone E, Hsia EC, Hsu B, Zhou Y, Goldstein N, Braun J. Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. J Rheumatol. 2016 Dec;43(12):2120-2130. doi: 10.3899/jrheum.160420. Epub 2016 Nov 1.
citation: Aletaha D, Alasti F, Smolen JS. Disease activity states of the DAPSA, a psoriatic arthritis specific instrument, are valid against functional status and structural progression. Ann Rheum Dis. 2017 Feb;76(2):418-421. doi: 10.1136/annrheumdis-2016-209511. Epub 2016 Jul 25.
citation: Kavanaugh A, van der Heijde D, Beutler A, Gladman D, Mease P, Krueger GG, McInnes IB, Helliwell P, Coates LC, Xu S. Radiographic Progression of Patients With Psoriatic Arthritis Who Achieve Minimal Disease Activity in Response to Golimumab Therapy: Results Through 5 Years of a Randomized, Placebo-Controlled Study. Arthritis Care Res (Hoboken). 2016 Feb;68(2):267-74. doi: 10.1002/acr.22576.
citation: Kavanaugh A, McInnes IB, Mease P, Krueger GG, Gladman D, van der Heijde D, Zhou Y, Lu J, Leu JH, Goldstein N, Beutler A. Clinical efficacy, radiographic and safety findings through 5 years of subcutaneous golimumab treatment in patients with active psoriatic arthritis: results from a long-term extension of a randomised, placebo-controlled trial (the GO-REVEAL study). Ann Rheum Dis. 2014 Sep;73(9):1689-94. doi: 10.1136/annrheumdis-2013-204902. Epub 2014 Apr 19.
citation: Helliwell PS, Kavanaugh A. Comparison of composite measures of disease activity in psoriatic arthritis using data from an interventional study with golimumab. Arthritis Care Res (Hoboken). 2014 May;66(5):749-56. doi: 10.1002/acr.22204.
citation: Kavanaugh A, McInnes IB, Krueger GG, Gladman D, Beutler A, Gathany T, Mack M, Tandon N, Han C, Mease P. Patient-reported outcomes and the association with clinical response in patients with active psoriatic arthritis treated with golimumab: findings through 2 years of a phase III, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken). 2013 Oct;65(10):1666-73. doi: 10.1002/acr.22044.
citation: Kavanaugh A, van der Heijde D, McInnes IB, Mease P, Krueger GG, Gladman DD, Gomez-Reino J, Papp K, Baratelle A, Xu W, Mudivarthy S, Mack M, Rahman MU, Xu Z, Zrubek J, Beutler A. Golimumab in psoriatic arthritis: one-year clinical efficacy, radiographic, and safety results from a phase III, randomized, placebo-controlled trial. Arthritis Rheum. 2012 Aug;64(8):2504-17. doi: 10.1002/art.34436.