Effects of Abatacept in Patients With Early Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to determine if abatacept is effective in the treatment of early rheumatoid arthritis.

Detailed Description
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Subcutaneous (SC)

Official Title
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A Phase 3B, Randomized, Double-Blind Clinical Trial to Evaluate the Efficacy and Safety of Abatacept SC in Combination With Methotrexate Compared to Methotrexate Monotherapy in Achieving Clinical Remission in Adults With Early Rheumatoid Arthritis Who Are Methotrexate Naive

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Abatacept
* Drug: Methotrexate
* Other: Abatacept Placebo
* Other: Methotrexate Placebo


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Rheumatoid arthritis (RA) diagnosis less than 6 months CRP > 3 mg/L or Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/h At least 3 swollen and 3 tender joints Anti-citrullinated protein antibodies (ACPA) positive Exclusion Criteria: At risk for tuberculosis Have acute infection Have chronic or recurrent bacterial or serious latent viral infection History of malignancies in the last 5 years except squamous skin, basal skin or cervical carcinoma Previous treatment with any conventional or biologic Disease-modifying anti rheumatic drugs (DMARD)

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: Combination Therapy: Abatacept + Methotrexate<br>Abatacept 125 mg subcutaneous injection once per week + Methotrexate at least 15mg per week tablet or capsule orally once per week | Drug: Abatacept<br> <br> Drug: Methotrexate<br> <br> |
| Active Comparator: Methotrexate treatment<br>Methotrexate at least 15mg per week tablet or capsule orally | Drug: Methotrexate<br> <br> |
| Placebo Comparator: Abatacept Placebo<br>Placebo for Abatacept subcutaneous injection once per week | Other: Abatacept Placebo<br> <br> |
| Placebo Comparator: Methotrexate Placebo<br>Placebo to match Methotrexate capsule orally once per week | Other: Methotrexate Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Simple Disease Activity Index (SDAI) Remission at Week 24 | Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Disease Activity Score (DAS)28 - C-reactive Protein (CRP) Remission at Week 24 | DAS28-CRP = Disease Activity Score 28 based on C-reactive protein DAS28-CRP Remission is defined as DAS28-CRP <= 2.6 Using a logistic regression model that includes treatment arm, stratification variable and baseline measure as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. | Week 24 | 
| Percentage of Participants in SDAI Remission at Week 52 | Simple Disease Activity Index (SDAI) is calculated using the following formula: TJC + SJC + PGA + MDGA + CRP (TJC = number of painful joints from 28 joints, SJC = number of swollen joints from 28 joints, PGA = patient global assessment on a visual analog scale 0-10 cm, MDGA = physician global assessment on a visual analog scale 0-10 cm, and CRP = c-reactive protein in mg/dL) SDAI Remission is defined as SDAI <= 3.3. Using a logistic regression model that includes treatment arm, randomization stratification factor, and baseline SDAI as continuous variable and point estimate of adjusted ORs, corresponding 95% CI and p-value was provided. SDAI total score range: 0 to 86. SDAI <= 3.3 indicates disease remission and SDAI >26 = high disease activity. | Week 52 | 
| Mean Change From Baseline in Radiographic Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijide Total Sharp Scores (TSS) at Week 52 | The Modified Total Sharp Score (mTSS) is calculated as the bilateral sum of erosion and Joint Space Narrowing (JSN) scores across all joints of the hands and feet.The score range for mTSS is 0-448. Higher scores indicate more joint damage. The mean change from baseline in TSS using modified Sharp/van der Heijide scores was assessed using a rank-based nonparametric ANCOVA model. | Week 52 | 
| Percentage of Participants in Boolean Remission at Week 52 | Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale). Logistic regression was used for this endpoint. | Week 52 |