Official Title: “A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Golimumab, a Fully Human Anti-TNFa Monoclonal Antibody, Administered Intravenously, in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy”

The primary purpose of this study is to assess the clinical effectiveness and safety of intravenous (IV- injection directly into the vein) golimumab infusions every 12 weeks in patients with active rheumatoid arthritis (RA) despite current MTX treatment. The secondary objectives of this study are to evaluate the effects on physical function, quality of life, and the pharmacological features of golimumab in subjects with active RA.

Study Type: Interventional

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

Though subcutaneously (SC- injections under the skin) administered golimumab has been shown to be effective in the treatment of RA, no large (Phase 3) clinical trial has yet been performed to support the use of or to determine the optimal dosage for maximal safety and effectiveness of golimumab when administered intravenously (into the vein). Such information would be important to physicians and patients who prefer IV administration of anti-TNF therapy to SC administration. The main purpose of this study is to assess the effects of golimumab on patients with Rheumatoid Arthritis. This study will assess the safety of intravenously administered golimumab and determine if there is a reduction of signs and symptoms (such as pain, stiffness, and tender and swollen joints) in patients with active Rheumatoid Arthritis who have been on a stable dose of Methotrexate (MTX) treatment. The effect of intravenously administered golimumab on physical function and the quality of life in patients with Rheumatoid Arthritis will also be assessed. This is a study of efficacy (effectiveness) and safety of IV administration of golimumab at 2 different doses (given with or without MTX) for at least 48 weeks in patients with active RA despite current MTX therapy.

Patients will receive 30 minute infusions of either 2 mg/kg or 4 mg/kg golimumab or placebo (sham) every 12 weeks. Doses of study drugs may be changed at Weeks 16 and/or 24 based upon how well individual patients respond to treatment. In the majority of cases, patients randomized (based on chance) to placebo will begin receiving 4 mg/kg golimumab infusions at Week 24.The study drugs received by the patients will remain unknown to patients and investigators until the last patient completes the Week 48 visit. The trial hypothesis is that the study treatment (2 mg/kg and/or 4 mg/kg golimumab with and/or without MTX) will be more effective in treatment of RA than MTX alone, as measured by >=50 percent improvement from baseline in American College of Rheumatology(ACR) scores at Week 14 (including number of tender and swollen joints) without any significant adverse events. Other measurements include DAS28 (Disease Activity Score including a 28-joint count) using CRP (C-Reactive Protein blood test) at week 14.   

Patients will receive a 30-minute IV infusion of either 2 mg/kg or 4 mg/kg golimumab or placebo at Weeks 0, 12 and 24, 36 and 48 with or without methotrexate. Most placebo patients will receive 4 mg/kg golimumab every 12 weeks beginning at Week 24.

Intervention(s) in this Clinical Trial

• Biological: golimumab; methotrexate
  • 2 mg/kg IV every 12 wks thru Wk48; methotrexate - continue dose from before study entry thru Wk48; golimumab - if early escape wk16, 2mg/kg IV at Wk16, 4mg/kg at Wk24 & every 12 wks thru Wk48; golimumab - if dose adjusted at wk 24, receive 4mg/kg IV at Wk24 and every 12 wks thru Wk 48
• Biological: golimumab; placebo
  • 2mg/kg IV every 12 wks thru Wk48; placebo - Placebo oral thru Wk48; methotrexate - if early escape, at Wk16 resume dose from prior to study thru Wk48; golimumab - if dose adjusted wk16 and 24, receive 4mg/kg IV at Wk24 & every 12 wks thru Wk48; methotrexate - if dose adjusted at wk 24, not early escape, resume dose prior to study thru Wk48
• Biological: golimumab; methotrexate
  • 4mg/kg IV every 12 wks thru Wk48; methotrexate - continue dose from before study entry thru Wk48
• Biological: golimumab; placebo
  • 4 mg/kg IV every 12 wks; placebo - placebo orally thru Wk 48 ( wk 16 if early escape); methotrexate - if early escape at Week 16: resume methotrexate dose from prior to study thru Wk48; methotrexate - if dose regimen adjustment: at Wk24 resume methotrexate regimen prior to study thru Wk48
• Drug: placebo; methotrexate
  • placebo IV every 12 wks thru Wk48 except early escape or dose regimen adjustment; golimumab - if early escape at Week 16: 4mg/kg IV at wks 16 and 24 then every 12 wks thru wk 48; golimumab - if dose regimen adjustment at wk 24: 4mg/kg IV and every 12 wks thru Wk 48; methotrexate - continue dose from before study entry thru Wk48
• Biological: golimumab; methotrexate
  • Study Extension: Subcutaneous 50 mg injection every 4 wks; methotrexate - Study Extension: Dr's discretion, maintain or adjust dose

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 001
• Experimental: 002
• Experimental: 003
• Experimental: 004
• Placebo Comparator: 005
• Experimental: 006

Primary Measures

• 1. A comparison of the proportion of patients who achieve an ACR 50 response at Week 14 between subjects receiving golimumab and those receiving placebo.
  • Time Frame: ACR 50 response at Week 14
    Safety Issue?: No

Secondary Measures

• 1.The proportion of patients who achieve an ACR 50 response at Week 24; 2. The proportion of patients who achieve an ACR 20 response at Week 14; 3. The proportion of patients with moderate or good response in DAS28 using CRP at Week 14.
  • Time Frame: ACR 50 response at Week 24, ACR 20 response at Week 14, DAS 28 response using CRP at week 14, change from baseline in the physical component summary score of the SF-36 at Week 14
    Safety Issue?: No

Inclusion Criteria:

• Have a diagnosis of active RA (according to the revised 1987 criteria of the ARA(American Rheumatism Association)
• Arnett et al, 1988) with at least 4 swollen and 4 tender joints for at least 3 months prior to screening
• Have been treated with and tolerated MTX at a dose of at least 15 mg/week for at least 3 months prior to screening, and have been on a stable MTX dose of >=15 mg/week and <= 25 mg/week for at least 4 weeks prior to screening
• If using non steroidal anti-inflammatory agents (such as naproxen) or other pain relievers for RA, 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. If currently not using corticosteroids, the subject must have not received oral corticosteroids for at least 2 weeks prior to first administration of study agent
• Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination and chest x-ray

Exclusion Criteria:

• No known hypersensitivity (severe allergy) to human immunoglobulin proteins or other components of golimumab
• No known clinically serious adverse reaction to a biologic anti-TNF agent
• No known history of latent or active granulomatous infection, including tuberculosis, histoplasmosis, or coccidioidomycosis, prior to screening
• No current signs or symptoms of severe, progressive, or uncontrolled kidney, liver, blood, gastrointestinal, glandular, lung, heart, nervous system, psychiatric, or brain disease
• No history of, or concurrent, congestive heart failure (CHF), including medically controlled, asymptomatic CHF
• No known cancer or history of cancer within the previous 5 years (with the exception of a nonmelanoma skin cancer that has been treated with no evidence of recurrence)

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 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00361335

Study ID Number: CR012781

ClinicalTrials.gov Identifier: NCT00361335

Health Authority: United States: Food and Drug Administration