A Study to Compare the Response to Treatment With Abatacept vs Adalimumab, on Background Methotrexate, in Adults With Early, Seropositive, and Shared Epitope-positive Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the superiority in efficacy of abatacept compared with adalimumab, on background methotrexate, in adults with early, seropositive, and shared epitope-positive rheumatoid arthritis and an inadequate methotrexate response.

Official Title
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A Randomized, Head-to-head, Single-blind Study to Compare the Response to Treatment With Subcutaneous Abatacept vs Adalimumab, on Background Methotrexate, in Adults With Early, Seropositive Rheumatoid Arthritis Who Have Shared Epitope HLA Class II Risk Alleles and Have an Inadequate Response to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Abatacept
* Drug: Adalimumab
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Early rheumatoid arthritis (RA), defined as symptoms of RA that started ≤ 12 months prior to screening and satisfied the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for the classification of RA at some point during the 12-month period Naïve to any targeted (biologic or nonbiologic) disease-modifying antirheumatic drugs (DMARDs), conventional synthetic DMARDs other than methotrexate (MTX), or investigational therapies for RA Treated with MTX for at least 12 weeks, with a stable dose of oral or parenteral MTX for at least 4 weeks prior to randomization Anti-cyclic citrullinated peptide-2 (Anti-CCP-2) test that is > 3× the upper limit of normal and are positive for rheumatoid factor (RF) according to central lab testing during screening At least a Disease Activity Score 28-joint count calculated using C-reactive protein (DAS28-CRP) ≥ 3.2 at screening At least 3 tender and at least 3 swollen joints at screening and at randomization Exclusion Criteria: Women who are breastfeeding Autoimmune disease other than RA (e.g., psoriasis, systemic lupus erythematosus [SLE], vasculitis, seronegative spondyloarthritis, inflammatory bowel disease, Sjogren's syndrome) or currently active fibromyalgia History of or current inflammatory joint disease other than RA (e.g., psoriatic arthritis, gout, reactive arthritis, Lyme disease) At risk for tuberculosis Recent acute infection History of chronic or recurrent bacterial infection (e.g., chronic pyelonephritis, osteomyelitis, bronchiectasis) History of infection of a joint prosthesis or artificial joint History of systemic fungal infections (such as histoplasmosis, blastomycosis, or coccidiomycosis) History of primary immunodeficiency Current clinical findings or a history of a demyelinating disorder 5 or more joints cannot be assessed for tenderness or swelling Other protocol-defined inclusion/exclusion criteria apply

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: Abatacept + Methotrexate<br> | Drug: Abatacept<br>* Abatacept SC (125 mg) once weekly<br>* Other names: Orencia®;Drug: Methotrexate<br>* Methotrexate oral/parenteral maximum tolerated dose (minimum 15 mg and maximum 25 mg weekly)<br>|
| Experimental: Arm 2: (Adalimumab + Methotrexate) followed by (Abatacept + Methotrexate)<br> | Drug: Abatacept<br>* Abatacept SC (125 mg) once weekly<br>* Other names: Orencia®;Drug: Adalimumab<br>* Adalimumab SC (40 mg) once every 2 weeks<br>* Other names: Humira®;Drug: Methotrexate<br>* Methotrexate oral/parenteral maximum tolerated dose (minimum 15 mg and maximum 25 mg weekly)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of shared epitope-positive (SE+) participants meeting 50% improvement in American College of Rheumatology criteria (ACR50) response |  | At week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of SE+ participants achieving Disease Activity Score 28-joint count calculated using C-reactive protein (DAS28-CRP) remission (DAS28-CRP < 2.6) |  | At week 24 | 
| Proportion of whole study population participants meeting ACR50 response |  | At week 24 | 
| Proportion of SE+ participants achieving Clinical Disease Activity Index (CDAI) remission (CDAI ≤ 2.8) |  | At week 24 | 
| Mean change from baseline in SE+ participant-reported pain by visual analog scale (VAS) |  | At week 24 | 
| Proportion of SE+ subset achieving 20% improvement in American College of Rheumatology criteria (ACR20) responses |  | Up to 104 weeks | 
| Proportion of SE+ whole population achieving ACR20 responses |  | Up to 104 weeks | 
| Proportion of SE+ subset achieving 50% improvement in American College of Rheumatology criteria (ACR50) responses |  | Up to 104 weeks | 
| Proportion of SE+ whole population achieving ACR50 responses |  | Up to 104 weeks | 
| Proportion of SE+ subset achieving 70% improvement in American College of Rheumatology criteria (ACR70) responses |  | Up to 104 weeks | 
| Proportion of SE+ whole population achieving ACR70 responses |  | Up to 104 weeks | 
| Proportion of SE+ subset achieving Disease Activity Score (DAS) remission |  | Up to 104 weeks | 
| Proportion of SE+ whole population achieving DAS remission |  | Up to 104 weeks | 
| Proportion of SE+ subset achieving Clinical Disease Activity Index (CDAI) remission |  | Up to 104 weeks | 
| Proportion of SE+ whole population achieving CDAI remission |  | Up to 104 weeks | 
| Proportion of SE+ subset achieving Simple Disease Activity Index (SDAI) remission over the Single-blind Treatment Period (SBTP) |  | Up to 104 weeks | 
| Proportion of SE+ subset achieving Simple Disease Activity Index (SDAI) remission over the Open-label Treatment Period (OLTP) |  | Up to 104 weeks | 
| Proportion of SE+ whole population achieving SDAI remission over the SBTP |  | Up to 104 weeks | 
| Proportion of SE+ whole population achieving SDAI remission over the OLTP |  | Up to 104 weeks | 
| Mean changes from baseline in DAS28-CRP |  | Up to 104 weeks | 
| Mean changes from baseline in CDAI |  | Up to 104 weeks | 
| Mean changes from baseline in SDAI over the SBTP |  | Up to 104 weeks | 
| Mean changes from baseline in SDAI over the OLTP |  | Up to 104 weeks | 
| Mean changes from baseline in the 7 ACR core components over the SBTP |  | Up to 104 weeks | 
| Mean changes from baseline in the 7 ACR core components over the OLTP |  | Up to 104 weeks | 
| Mean change from baseline in 36-item Short Form Survey (SF-36) in SE+ subset at week 24 and week 104 |  | Up to 104 weeks | 
| Mean change from baseline in SF-36 in SE+ whole population at week 24 and week 104 |  | Up to 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abatacept, Adalimumab, BMS-188667, Humira®, Methotrexate, Orencia®, Rheumatoid Arthritis