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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlledTrial of Golimumab, a Fully Human Anti-TNFa MonoclonalAntibody, Administered Subcutaneously, in Methotrexate-naive Subjects With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Placebo injections
* Drug: Placebo capsules
* Drug: Methotrexate capsules
* Biological: Golimumab 50 mg injections
* Biological: Golimumab 100 mg injections


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Placebo + Methotrexate<br>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. | Drug: Placebo injections<br>* SC injections<br>Drug: Methotrexate capsules<br>* Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.<br>Biological: Golimumab 50 mg injections<br>* SC injections<br>Biological: Golimumab 100 mg injections<br>* SC injections<br>|
| Experimental: Group 2: Golimumab 100 mg + Placebo<br>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. | Drug: Placebo capsules<br>* Placebo capsules will be filled with microcrystalline cellulose (Avicel PH 102).<br>Drug: Methotrexate capsules<br>* Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.<br>Biological: Golimumab 50 mg injections<br>* SC injections<br>Biological: Golimumab 100 mg injections<br>* SC injections<br>|
| Experimental: Group 3: Golimumab 50 mg + Methotrexate<br>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. | Drug: Methotrexate capsules<br>* Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.<br>Biological: Golimumab 50 mg injections<br>* SC injections<br>Biological: Golimumab 100 mg injections<br>* SC injections<br>|
| Experimental: Group 4: Golimumab 100 mg + Methotrexate<br>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. | Drug: Methotrexate capsules<br>* Methotrexate capsules will be filled with microcrystalline cellulose (Avicel PH 102) and a 2.5 mg methotrexate tablet.<br>Biological: Golimumab 50 mg injections<br>* SC injections<br>Biological: Golimumab 100 mg injections<br>* SC injections<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24 | ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain by the Visual Analogue Scale (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity VAS (0-10 cm) c. Physician's Global Assessment of Disease Activity VAS (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein. | Week 24 | 
| Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52 | The vdH-S score is the sum of the joint erosion score and the joint-space narrowing (JSN) score. The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24 | ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 20 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain by the Visual Analogue Scale (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity VAS (0-10 cm) c. Physician's Global Assessment of Disease Activity VAS (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein. | Week 24 | 
| Number of Patients With Abnormal Baseline C-reactive Protein (CRP) Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24 | ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in: 1. Swollen joint count (66 joints) and tender joint count (68 joints) 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Patient's assessment of pain by the Visual Analogue Scale (VAS) (0-10 cm) b.Patient's Global Assessment of Disease activity VAS (0-10 cm) c. Physician's Global Assessment of Disease Activity VAS (0-10 cm) d. Patient's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein. | Week 24 | 
| Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 52 in Patients With Abnormal C-reactive Protein (CRP Greater Than 1.0 mg/dL) at Baseline | The vdH-S score is the sum of the joint erosion score and the joint-space narrowing (JSN) score. The total score ranges from 0 (best) to 448 (worst) with higher scores indicating more joint damage. | Baseline and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Methotrexate Naïve, subcutaneous injection