An Effectiveness and Safety Study of Intravenous Golimumab in Patients With Active Rheumatoid Arthritis Despite Treatment With Methotrexate Therapy
This study has been completed.
Sponsor:
Centocor, Inc.
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00973479
First received: September 4, 2009
Last updated: May 21, 2013
Last verified: May 2013
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Purpose
The purpose of this study is to evaluate clinical effectiveness and safety of golimumab with methotrexate (MTX) in the treatment of rheumatoid arthritis (RA) when compared to MTX alone.
| Condition | Intervention | Phase |
|---|---|---|
|
Arthritis, Rheumatoid |
Drug: Golimumab Other: Placebo Drug: methotrexate (MTX) |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFalpha Monoclonal Antibody, Administered Intravenously, in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy |
Resource links provided by NLM:
Further study details as provided by Centocor, Inc.:
Primary Outcome Measures:
- Number of participants who achieved American College of Rheumatology (ACR) 20 response at Week 14 [ Time Frame: Week 14 ] [ Designated as safety issue: No ]An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in: 1. Swollen (66 joints) and tender (68 joints) joint counts; 2. greater than or equal to 20 percentage improvement in 3 of the following 5 assessments: a. Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm) b. Participant's global assessment of disease activity by VAS (0-10 cm) c. Physician's global assessment of disease activity by VAS (0-10 cm) d. Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein.
Secondary Outcome Measures:
- Number of participants With Disease Activity Index score 28 (DAS28) using C-reactive protein (CRP) response at Week 14 [ Time Frame: Week 14 ] [ Designated as safety issue: No ]DAS28 using CRP is an index to measure the disease activity in participants with rheumatoid arthritis combining tender joints (28 joints), swollen joints (28 joints), CRP, and participant's global assessment of disease activity. The DAS28 score ranges from 0 (best) to 10 (worst). DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Higher scores indicate worsening.
- Change from baseline in Health Assessment Questionnaire (HAQ) score at Week 14 [ Time Frame: Baseline (Week 0) and Week 14 ] [ Designated as safety issue: No ]The HAQ is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). HAQscore on a scale ranges from 0 (no disability) to 3 (completely disabled). Higher scores indicate worsening.
- Number of participants who achieved American College of Rheumatology (ACR) 50 response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]An ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in: 1. Swollen (66 joints) and tender (68 joints) joint counts; 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm) b. Participant's global assessment of disease activity by VAS (0-10 cm) c. Physician's global assessment of disease activity by VAS (0-10 cm) d. Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein.
- Change from baseline in total van der Heijde modified Sharp (vdH-S) score at Week 24 [ Time Frame: Baseline (Week 0) and Week 24 ] [ Designated as safety issue: No ]The vdH-S score is the sum of joint erosion score and joint-space narrowing (JSN) score. The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage.
- Number of participants with adverse events [ Time Frame: Up to Week 112 ] [ Designated as safety issue: Yes ]
| Enrollment: | 592 |
| Study Start Date: | September 2009 |
| Study Completion Date: | February 2013 |
| Primary Completion Date: | March 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Group I
Participants will receive golimumab at Weeks 0, 4, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.
|
Drug: Golimumab
Participants will receive 2 mg/kg of golimumab intravenously over 30 ± 10 minutes. Group 1: at Weeks 0, 4, and every 8 weeks thereafter (up to Week 100). Group II: Weeks 24, 28, and every 8 weeks thereafter (up to Week 100); Early escape: at Week 16, 20 and every 8 weeks thereafter (up to Week 100).
Other: Placebo
Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.
Drug: methotrexate (MTX)
Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.
|
|
Placebo Comparator: Group II
Participants will receive placebo at Weeks 0, 4, 12, and 16. Participants will cross over to golimumab at Week 24, and receive administrations at Weeks 24, 28, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will be eligible for early escape (receive golimumab) at Week 16 if they demonstrate a less than 10 percent improvement in both tender and swollen joint count. These participants will receive golimumab at Weeks 16, 20, and every 8 weeks thereafter.
|
Drug: Golimumab
Participants will receive 2 mg/kg of golimumab intravenously over 30 ± 10 minutes. Group 1: at Weeks 0, 4, and every 8 weeks thereafter (up to Week 100). Group II: Weeks 24, 28, and every 8 weeks thereafter (up to Week 100); Early escape: at Week 16, 20 and every 8 weeks thereafter (up to Week 100).
Other: Placebo
Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.
Drug: methotrexate (MTX)
Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.
|
Detailed Description:
This is a randomized (study medication is assigned by chance), double-blind (neither physician nor participants knows the treatment that the participant receives), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), multicenter, 2-arm (2 groups) study of golimumab in participants with active RA despite concurrent MTX therapy. Approximately 564 participants will be randomly allocated to 1 of 2 treatment groups in a 2:1 ratio ie, Group 1(approximately 376 participants will receive golimumab + MTX) and Group 2 (approximately 188 participants will receive MTX + placebo). Total duration of study for each participant is 112 weeks. Safety will be evaluated by assessment of adverse events, tuberculosis testing and blood testing.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of rheumatoid arthritis (RA) for at least 3 months prior to screening
- 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 been on a stable MTX dose of 15 mg/week to 25 mg/week for at least 4 weeks prior to screening
- Have an active RA, as defined by disease activity with at least 6 swollen and 6 tender joints, at the time of screening and at baseline
- C-Reactive Protein greater than or equal to 1.0 mg/dL at screening
- No history of latent or active tuberculosis prior to screening
Exclusion Criteria:
- Other inflammatory diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or lyme disease
- Treated with disease modifying agents (other than methotrexate)/systemic immunosuppressives (eg, D-penicillamine, hydroxychloroquine, chloroquine, oral or parenteral gold, sulfasalazine, leflunomide, azathioprine, cyclosporine, mycophenolate mofetil) during the 4 weeks prior to first administration of study agent
- Received intra-articular (in the joint), intramuscular (in the muscle), or intravenous corticosteroids, including adrenocorticotropic hormone, during the 4 weeks prior to first administration of study agent
- Known allergy to human immunoglobulin proteins or other components of golimumab
- Received any commercial or investigational anti-tumor necrosis factor alpha therapy such as but not exclusively infliximab, golimumab, adalimumab or etanercept
Contacts and Locations More Information
No publications provided
| Responsible Party: | Centocor, Inc. |
| ClinicalTrials.gov Identifier: | NCT00973479 History of Changes |
| Other Study ID Numbers: | CR015784, CNTO148ART3001, 2008-006064-11 |
| Study First Received: | September 4, 2009 |
| Last Updated: | May 21, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Centocor, Inc.:
|
Arthritis, Rheumatoid Active rheumatoid arthritis Golimumab CNTO148 |
Anti-TNFalpha monoclonal antibody Methotrexate Intravenous |
Additional relevant MeSH terms:
|
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Antibodies, Monoclonal Methotrexate Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Abortifacient Agents, Nonsteroidal |
Abortifacient Agents Reproductive Control Agents Therapeutic Uses Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Antirheumatic Agents Nucleic Acid Synthesis Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013