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

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 not been previously treated 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 who have not been previously treated 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 van der Heijde Modified Sharp (vdH-S) score, 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 rheumatoid arthritis. The vdH-S score is a measurement of the amount of joint damage in a subject as seen by x-ray. Other secondary measures of effectiveness include the Health Assessment Questionnaire (HAQ), which is a series of questions that measure a subject's impairment in physical function caused by RA.

Golimumab 50 mg or 100 mg, or placebo injections under the skin every 4 weeks until Week52.

Methotrexate (MTX) or placebo capsules will be given in addition. At Week52, subjects on MTX alone with joint pain or swelling get golimumab 50mg, and all subjects receive golimumab for about 4 more years.

Intervention(s) in this Clinical Trial

• Drug: placebo; methotrexate
  • SC injections every 4 wks from wk0 to wk 48 (unless early escape at wk 28);methotrexate-10-20mg for up to 5 years;golimumab-If early escape, 50mg sc injection every 4 wks from wk 28 up to 5 yrs; golimumab-Dr's discretion after unblinding, dose adjust from 50 to 100 mg
• Drug: golimumab; methotrexate
  • 100mg sc injection every 4 wks for up to 5 yrs;methotrexate- 4-8 capsules weekly during blinded period;methotrexate - If early escape may start 10mg weekly during blinded period; methotrexate - Dr's discretion, adjust weekly dose after unblinding
• Biological: golimumab
  • 50 mg sc injections every 4 wks from wk0-48 (Wk 28 if early escape);Methotrexate - 10-20 mg for up to 5 years; Golimumab - If early escape, 100 mg beginning at wk 28 for up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjust from 50 to100 mg
• Biological: Golimumab
  • 100 mg sc injections every 4 wks from wk 0 up to 5 yrs; Methotrexate - 10-20 mg for up to 5 years

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) 50 response at Week 24, and the change from baseline in van der Heijde Modified Sharp (vdH-S) score at Week 52.
  • Time Frame: Week 24 and Week 52
    Safety Issue?: No

Secondary Measures

• The secondary outcomes are change from baseline in HAQ at Week52, ACR20 response at Week24, change from baseline in vdH-S score at Week52 in subjects with abnormal CRP at baseline, and ACR50 response at Week24 in subjects with abnormal CRP at baseline.
  • Time Frame: Week 24 and Week 52
    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 first administration of study agent
• Are methotrexate (MTX)-naïve (ie, have not received more than 3 weekly doses of MTX for RA at any time)
• 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

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 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 September 08, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00264537

Study ID Number: CR006331

ClinicalTrials.gov Identifier: NCT00264537

Health Authority: United States: Food and Drug Administration