Abatacept Post-marketing Clinical Study in Japan

Study Overview
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Brief Summary
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The purpose of this study is to compare the clinical efficacy including joint damage progression and safety of Abatacept plus Methotrexate (MTX) to placebo plus MTX.

Official Title
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A Phase 4, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Abatacept in Combination Therapy With Methotrexate vs. Methotrexate Alone in Subjects With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Abatacept
* Drug: Placebo matching with Abatacept
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MTX inadequate responder Biologic Naïve Functional class I, II or III ≥6 swollen and ≥6 tender joints C-reactive protein (CRP) ≥2.0mg/dl or erythrocyte sedimentation rate (ESR) ≥28 mm/hr Anti-cyclic citrullinated peptide (CCP) antibody positive Have erosion Exclusion Criteria: Any other rheumatic disease Active angiitis on main organs excluding rheumatoid nodule

Ages Eligible for Study
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Minimum Age: 20 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: Abatacept + Methotrexate (MTX)<br>Abatacept 10 mg/kg solution intravenous (IV) infusion, once monthly for 12 months Methotrexate ≥6 mg/week for 12 months | Biological: Abatacept<br> <br> * Other names: BMS-188667 (Orencia);Drug: Methotrexate<br> <br> |
| Placebo Comparator: Group 2: Placebo matching with Abatacept + Methotrexate<br>Placebo matching with Abatacept 0 mg/kg solution, intravenous (IV) infusion once monthly for 12 months Methotrexate ≥6 mg/week for 12 months | Drug: Placebo matching with Abatacept<br> <br> Drug: Methotrexate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology (ACR) 20% response rate |  | 4 months (week 16) | 
| Change from baseline in Total Sharp Score (TSS) using the Modified van der Heijde Sharp (vdH-S) method to 6 months (Week 24) |  | Baseline (Day 1), 6 months (Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Disease Activity Score-28 (DAS28)-CRP to 4 months (Week16) |  | Baseline (Day 1), 4 months (Week 16) | 
| Non-progressors rate for the structural damage | The non-progressors rate is defined as the proportion of subjects meeting the change from baseline in the TSS at 6 months less than or equal to the smallest detectable difference (SDD) and/or the smallest detectable change (SDC) | Baseline (Day 1), 6 months (Week 24) | 
| ACR 50 response rates |  | 4 months (Week16) | 
| ACR 70 response rates |  | 4 months (Week16) | 
| Safety and tolerability will be measured based on clinical Adverse Events, vital signs, and laboratory abnormalities |  | 12 months (Week52) |