Official Title: “A Multicenter, Randomized, Double-Blind, Placebo-controlledTrial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously, in Subjects With ActiveRheumatoid Arthritis Despite Methotrexate Therapy”

The purpose of this study is to evaluate the efficacy and safety of golimumab, alone or in combination with methotrexate, as compared to methotrexate alone in rheumatoid arthritis subjects who have active rheumatoid arthritis despite treatment with methotrexate

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Golimumab is a fully human protein (antibody) which binds to tumor necrosis factor (TNFα).

TNFα 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 TNFα (anti-TNFα 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-TNFα drug, golimumab, at 2 doses, injected under the skin every 4 weeks, alone or in combination with methotrexate, compared with methotrexate alone, in subjects with active RA despite treatment with methotrexate. The study hypothesis is that golimumab, alone or in combination with methotrexate, will be more effective in treatment of RA than methotrexate alone, as measured by the American College of Rheumatology (ACR) response criteria and change from baseline in the Health Assessment Questionnaire (HAQ), without causing unacceptable significant adverse effects. The ACR response criteria were designed to determine the percentage of subjects who have achieved a certain level of improvement in their signs and symptoms of RA. The HAQ is a series of questions that measure a subject's impairment in physical function caused by RA. Other secondary measures of effectiveness include the van der Heijde Modified Sharp (vdH-S) score, which is a measurement of the amount of joint damage in a subject as seen by x-ray.

Golimumab 50 mg or 100 mg or placebo injections under the skin every 4 weeks through week 20.

Methotrexate or placebo capsules will be given in addition. At Week 24, all subjects receive golimumab 50mg or 100mg injections, and golimumab continues for all groups for about 4 and a half more years.

Intervention(s) in this Clinical Trial

• Drug: placebo; methotrexate ; golimumab
  • sc injections every 4 wks through Week 20 (or Week 16 if early escape); methotrexate - 15-25mg every 4 wks up to 5 yrs; golimumab - If early escape, 50mg sc injs every 4 wks beginning wk 16 up to 5 yrs; golimumab - 50 mg sc injections every 4 wks beginning wk 24 up to 5 yrs (unless eary escape); golimumab - Dr's discretion after unblinding, dose adjust from 50 to 100mg
• Biological: golimumab; placebo
  • 100 mg sc injections every 4 wks from wk 0 up to 5 yrs; placebo - 7-10 capsules weekly during blinded period (or wk 16 if early escape); methotrexate - If early escape, 15-25mg weekly beginning wk 16 up to 5 yrs; methotrexate - Dr's discretion, adjust weekly dose after unblinding
• Biological: Golimumab
  • 50 mg every 4 wks from wk 0 up to 5 yrs (unless early escape at wk 16); Methotrexate - 15-25 mg for up to 5 years; Golimumab - If early escape,100 mg sc injs every 4 wks beginning wk 16 up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjust from 50 to100mg
• Biological: Golimumab
  • 100 mg sc injections every 4 wks from wk 0 up to 5 yrs; Methotrexate - 15-25 mg weekly from wk 0 up to 5 yrs

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 001
• Experimental: 002
• Experimental: 003
• Experimental: 004

Primary Measures

• The primary outcomes are American College of Rheumatology (ACR) 20 response at Week 14, and change from baseline in the Health Assessment Questionnaire (HAQ) at Week 24.
  • Time Frame: Week 14 and Week 24
    Safety Issue?: No

Secondary Measures

• The secondary outcomes are change from baseline in van der Heijde-Sharp (vdH-S) score at Week24, Disease Activity Score (DAS) 28 response (using C-reactive protein) at Week14, ACR20 response at Week 24, change from baseline in HAQ at Week14.
  • Time Frame: Week 14 and Week 24
    Safety Issue?: No

Inclusion Criteria:

• Have a diagnosis of rheumatoid arthritis (RA) (according to the revised 1987 criteria of the ACR) for at least 3 months prior to screening
• Must have been treated with and tolerated methotrexate (MTX) at a dose of at least 15mg/week for at least 3 months prior to screening, and have a MTX dose of >=15mg/week and <=25mg/week and stable for at least 4 weeks 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, and at least 2 of the following 4 criteria: a)C-reactive protein (CRP) >=1.5 mg/dL at screening or erythrocyte sedimentation rate (ESR) by Westergren method of >= 28 mm in the first hour at screening or baseline, b)Morning stiffness of >= 30 minutes at screening and baseline, c)Bone erosion by x-ray and/or MRI prior to first administration of study agent, d)Anti-cyclic citrullinated peptide (anti-CCP) antibody-positive or rheumatoid factor (RF) positive at screening
• 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:

• Can not have inflammatory diseases other than RA that might confound the evaluation of the benefit of golimumab therapy
• No treatment with disease-modifying anti-rheumatic drugs (DMARDs)/systemic immunosuppressives other than MTX, during the 4 weeks prior to the first administration of study agent
• No prior treatment with biologic anti-TNF drugs (infliximab, etanercept, adalimumab)
• No history of, or ongoing, chronic or recurrent infectious disease
• No serious infection within 2 months prior to first administration of study agent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Centocor, Inc.

Overall Clinical Trial Officials and Contacts

Centocor, Inc. Clinical Trial Study Director Centocor, Inc.  

Information obtained from ClinicalTrials.gov on August 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00264550

Study ID Number: CR006343

ClinicalTrials.gov Identifier: NCT00264550

Health Authority: United States: Food and Drug Administration