An Efficacy and Safety Study of Golimumab in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy

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 (MTX), as compared to methotrexate alone in rheumatoid arthritis (RA) patients who have active rheumatoid arthritis despite treatment with MTX.

This is a randomized (treatment is assigned by chance), double-blind (neither the physician nor the patient is aware of the received treatment), placebo-controlled study of multiple subcutaneous (SC) administrations of golimumab at 2 doses as monotherapy or in combination with MTX in patients with active RA despite treatment with MTX. The duration of participation in the study for an individual patient will be upto 268 weeks. The patients will be randomly assigned in a 3:3:2:2 ratio to receive golimumab 50 mg or 100 mg or placebo injections under the skin every 4 weeks through week 20 and methotrexate or placebo capsules will be given in addition. At Week 24, all subjects will receive golimumab 50mg or 100mg injections, and golimumab continues for all groups for about 4 and a half more years. At Week 16 any patient in the study who meets criteria for < 20% improvement from baseline in both swollen and tender joint count will enter early escape in a double-blinded fashion. Treatment during the long-term extension will start at Week 52 and continue every 4 weeks thereafter for a total of approximately 5 years from the initial (Week 0) administration of study agent. Patients will return for scheduled follow-up visits generally every 12 weeks for a total length of follow-up of approximately 5 years from the first administration of the study drug.

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 15 mg/week for at least 3 months prior to screening, and have a MTX dose of >=15 mg/week and <=25 mg/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 magnetic resonance imaging (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:

• Have inflammatory diseases other than RA that might confound the evaluation of the benefit of golimumab therapy
• Have had 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
• Have had prior treatment with biologic anti-tumor necrosis factor (TNF) drugs (infliximab, etanercept, adalimumab)
• Have had history of, or ongoing, chronic or recurrent infectious disease.
• Have serious infection within 2 months prior to first administration of study agent
• Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening