A Study of the Safety and Efficacy of Golimumab in Subjects With Rheumatoid Arthritis That Are Methotrexate-naive

Centocor Ortho Biotech

Status and phase: Completed; Phase 3

Conditions: Rheumatoid Arthritis

Treatments: Biological: Golimumab 100 mg injections; Drug: Placebo injections; Biological: Golimumab 50 mg injections; Drug: Methotrexate capsules; Drug: Placebo capsules

Study type: Interventional

Funder types: Industry

Identifiers

NCT00264537

GO-BEFORE

C0524T05

CR006331

Details and patient eligibility

About

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.

Full description

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

Enrollment: 637 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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637 participants in 4 patient groups

Group 1: Placebo + Methotrexate

Experimental group

Description:

Placebo subcutaneous injections (SC) every 4 weeks from Week 0 for up to 5 years (unless early escape at week 28); Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; Golimumab - if early escape, 50 mg SC injections every 4 weeks from Week 28 up to 5 years; Golimumab - Dr's discretion after unblinding (in participants receiving methotrexate plus placebo), 50 mg SC injections every 4 weeks up to 5 years; Golimumab- Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Treatment:

Drug: Methotrexate capsules

Biological: Golimumab 50 mg injections

Biological: Golimumab 100 mg injections

Drug: Placebo injections

Group 2: Golimumab 100 mg + Placebo

Experimental group

Description:

Golimumab 100 mg SC injections every 4 weeks from Week 0 for up to 5 years; placebo capsules weekly from Week 0 for up to 5 years (unless early escape at Week 28); Methotrexate - if early escape, 10 to 20 mg weekly from Week 28 up to 5 years; Methotrexate - Dr's discretion after unblinding (in participants receiving golimumab plus placebo) 10 to 20 mg weekly for up to 5 years; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Treatment:

Drug: Placebo capsules

Drug: Methotrexate capsules

Biological: Golimumab 50 mg injections

Biological: Golimumab 100 mg injections

Group 3: Golimumab 50 mg + Methotrexate

Experimental group

Description:

Golimumab 50 mg SC injections every 4 weeks from Week 0 for up to 5 years (unless early escape at week 28); Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; Golimumab - if early escape, 100 mg SC injections every 4 weeks from Week 28 for up to 5 yrs; Golimumab - Dr's discretion after unblinding, dose adjusted from 50 to 100 mg and from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Treatment:

Drug: Methotrexate capsules

Biological: Golimumab 50 mg injections

Biological: Golimumab 100 mg injections

Group 4: Golimumab 100 mg + Methotrexate

Experimental group

Description:

Golimumab 100 mg SC injections every 4 weeks from Week 0 for up to 5 years; Methotrexate - 10 to 20 mg weekly from Week 0 for up to 5 years; Golimumab - Dr's discretion after unblinding, dose adjusted from 100 to 50mg. Duration of the blinded period will be until the week-52 database lock.

Treatment:

Drug: Methotrexate capsules

Biological: Golimumab 50 mg injections

Biological: Golimumab 100 mg injections