Clinical trial NCT00299546: A Study of the Safety and Efficacy of Golimumab (CNTO 148) in Subjects With Active Rheumatoid Arthritis Previously Treated With Biologic Anti-TNFa Agent(s)
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, a Fully Human Anti-TNFa Monoclonal Antibody, Administered Subcutaneously in Subjects With Active Rheumatoid Arthritis and Previously Treated With Biologic Anti- TNFa Agent(s)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Keywords: Rheumatoid Arthritis
Anti-TNFa agents
subcutaneous injection
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
First posted: 2006-03-07
Enrollment: 461
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 efficacy and safety of golimumab (CNTO 148) in subjects who have active rheumatoid arthritis and have been treated previously with at least 1 dose of a biologic anti-TNFa agent (etanercept, adalimumab or infliximab).

Detailed description: Golimumab is a fully human protein (antibody) which binds to tumor necrosis factor-alpha (TNFa). TNFa is increased in patients with rheumatoid arthritis (RA), and plays a major role in causing the joint pain, swelling and damage from RA. Other marketed drugs that target TNFa (anti-TNFa drugs) have been shown to be effective in reducing the symptoms, signs and joint damage of RA, but have limitations with respect to safety and ease of use. This is a randomized, double-blind, placebo-controlled trial of the efficacy and safety of a new anti-TNFa drug, golimumab, at 2 doses, injected under the skin every 4 weeks in subjects with active RA previously treated with at least 1 dose of a biologic anti-TNFa agent (etanercept, adalimumab or infliximab). Concomitant therapy with methotrexate, sulfasalazine and/or hydroxychloroquine is permitted if the subject has tolerated these medications for at least 12 weeks prior to the first administration of study drug and is on a stable dose for at least 4 weeks prior to the first administration of study agent. The study hypothesis is that golimumab will be a safe and effective treatment for RA in subjects with active RA previously treated with at least one biologic anti-TNFa agent as measured by the American College of Rheumatology (ACR) response criteria, the Disease Activity Score 28 (DAS28) responses and the change from baseline in Health Assessment Questionnaire (HAQ), without causing unacceptable significant adverse effects. The ACR response criteria were designed to assess the level of improvement in the signs and symptoms of RA. The DAS28 responses also measure improvement in the signs and symptoms of RA using the joint examination and laboratory testing. The HAQ is a series of questions that measure a subject's impairment in physical function caused by RA. Patients will receive golimumab 50 mg or 100 mg or placebo injections under the skin every 4 weeks until Week 24. After Week 24, all subjects receive golimumab 50 mg or 100 mg injections, and golimumab continues for all groups every 4 weeks for about 4 and a half more years.

Eligibility criteria: Inclusion Criteria:

* Patients have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ACR) for at least 3 months prior to screening
* Have active RA as defined by persistent disease activity with at least 4 swollen and 4 tender joints, at the time of screening and baseline
* Must have been previously treated with at least one dose of etanercept, adalimumab, or infliximab
* If currently using methotrexate, sulfasalazine and/or hydroxychloroquine must have tolerated these agents for at least 12 weeks and be on a stable dose for at least 4 weeks prior to the first administration of study agent
* If using NSAIDs or other analgesics must be on a stable dose for at least 2 weeks prior to the first administration of study agent
* If using oral corticosteroids must be on a stable dose equivalent to \<= 10 mg of prednisone/day for at least 2 weeks prior to first administration of study agent
* Are considered eligible according to specified tuberculosis (TB) screening criteria.

Exclusion Criteria:

* Patients cannot have other inflammatory diseases other than RA that might interfere with the evaluation of the benefit of golimumab therapy
* No history of treatment with natalizumab, rituximab or cytotoxic agents
* No history of demyelinating diseases such as multiple sclerosis or optic neuritis or of concurrent congestive heart failure (CHF), lymphoproliferative disease, known malignancy or history of malignancy within the previous 5 years (with the exception of a nonmelanoma skin cancer that has been treated with no evidence of recurrence)
* No history of, or ongoing, chronic or recurrent infectious disease
* No serious infection within 2 months prior to first administration of study agent.

Primary outcomes:
measure: American College of Rheumatology (ACR) 20 Response at Week 14.
timeFrame: Week 14
Secondary outcomes:
measure: American College of Rheumatology (ACR) 50 Response at Week 14
timeFrame: Week 14
measure: Disease Activity Index Score 28 (DAS 28) (Using C-reactive Protein) Response at Week 14
timeFrame: Week 14
measure: American College of Rheumatology (ACR) 20 at Week 24
timeFrame: From Baseline to Week 24
measure: Health Assessment Questionnaire (HAQ) Score at Week 24
timeFrame: From Baseline to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Paradise Valley
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Torrance
country: United States
state: California
city: Upland
country: United States
state: California
city: Trumbull
country: United States
state: Connecticut
city: Aventura
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Largo
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Tamarac
country: United States
state: Florida
city: Moline
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Cedar Rapids
country: United States
state: Iowa
city: Witchita
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Wheaton
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: Syracuse
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Mayfield
country: United States
state: Ohio
city: Duncansville
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Knoxville
country: United States
state: Tennessee
city: Fort Worth
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: Arlington
country: United States
state: Virginia
city: Spokane
country: United States
state: Washington
city: Brookfield
country: United States
state: Wisconsin
city: Racine
country: United States
state: Wisconsin
city: Adelaide
country: Australia
city: Cotton Tree
country: Australia
city: Melbourne
country: Australia
city: Graz
country: Austria
city: Lainz/Wien N/A
country: Austria
city: Wien
country: Austria
city: Victoria
country: Canada
state: British Columbia
city: Winnipeg
country: Canada
state: Manitoba
city: St. John'S
country: Canada
state: Newfoundland and Labrador
city: Kitchener
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Sainte Foy
country: Canada
state: Quebec
city: Claire
country: Canada
city: Helsinki
country: Finland
city: Hyvinkaa
country: Finland
city: Jyvalskyla
country: Finland
city: Baden-Baden
country: Germany
city: Berlin
country: Germany
city: Erlangen
country: Germany
city: Hamburg
country: Germany
city: Herne
country: Germany
city: Köln
country: Germany
city: München
country: Germany
city: Vogelsang-Gommern
country: Germany
city: Würzburg
country: Germany
city: Maastricht
country: Netherlands
city: Auckland
country: New Zealand
city: Rotorua
country: New Zealand
city: Timaru
country: New Zealand
city: Santander
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Leeds
country: United Kingdom
city: London
country: United Kingdom
city: Oxford
country: United Kingdom
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Vieira MC, Zwillich SH, Jansen JP, Smiechowski B, Spurden D, Wallenstein GV. Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results From a Network Meta-analysis. Clin Ther. 2016 Dec;38(12):2628-2641.e5. doi: 10.1016/j.clinthera.2016.11.004. Epub 2016 Nov 24.
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: Smolen JS, Kay J, Doyle M, Landewe R, Matteson EL, Gaylis N, Wollenhaupt J, Murphy FT, Xu S, Zhou Y, Hsia EC. Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor alpha inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study. Arthritis Res Ther. 2015 Jan 22;17(1):14. doi: 10.1186/s13075-015-0516-6.
citation: Smolen JS, Kay J, Doyle MK, Landewe R, Matteson EL, Wollenhaupt J, Gaylis N, Murphy FT, Neal JS, Zhou Y, Visvanathan S, Hsia EC, Rahman MU; GO-AFTER study investigators. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009 Jul 18;374(9685):210-21. doi: 10.1016/S0140-6736(09)60506-7. Epub 2009 Jun 26.