A Study to Evaluate Biomarkers to Predict Efficacy of Abatacept in Rheumatoid Arthritis

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate if baseline levels of T cell associated biomarkers predict efficacy of abatacept during 24 weeks of treatment in patients with moderate to severe active Rheumatoid Arthritis (RA) who have had an inadequate response to conventional disease modifying anti-rheumatic drugs (cDMARDs)

Official Title
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Phase IV Open-Label Study to Evaluate Biomarkers to Predict the Efficacy of Abatacept in Subjects With Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Abatacept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-nursing female Age 18 years or greater Body weight less than or equal to 120 kg Classification of Rheumatoid Arthritis according to the 1987 ACR criteria or 2010 ACR/EULAR criteria Symptoms of Rheumatoid Arthritis present for at least 3 months and less that 10 years prior to Screening. Clinical Disease Activity Index (CDAI) greater than or equal to 16, corresponding to moderate to severe disease activity. Patients taking oral DMARDs must be on stable doses of DMARDs for at least 4 weeks prior to Abatacept initiation Treatment within the past year with either methotrexate, leflunomide, hydroxychloroquine and/or sulfasalazine for greater than or equal to 8 weeks. Patients who have received one prior Tumor necrosis factor (TNF) inhibitor must have discontinued etanercept, infliximab, adalimumab, certolizumab, or golimumab for at least 6 months prior to screening. Patients taking oral corticosteroids, the dose must be less than or equal to 5mg per day (prednisone or equivalent) Females of child bearing potential and males with female partners of child bearing potential may participate in this study only if using a reliable means of contraception Exclusion Criteria: Previous treatment with Abatacept (Orencia) Previous treatment with rituximab, tocilizumab, tofacitinib, sarilumab, or anakinra Previous treatment with IV immunoglobulin, plasmapheresis, or alkylating agents such as cyclophosphamide Intraarticular or parenteral corticosteroids within 4 weeks of screening Rheumatic autoimmune disease other than Rheumatoid Arthritis, including Systemic Lupus Erythematosus, primary Sjogren syndrome, spondyloarthritis, systemic sclerosis, dermatomyositis, mixed connective tissue disease, or vasculitis Non-rheumatic auto-immune disease including inflammatory bowel disease, psoriasis, multiple sclerosis Recurrent or chronic bacterial, viral, fungal, mycobacterial, or other infections including Human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, latent tuberculosis (TB) (TB not adequately treated) Primary or secondary immunodeficiency Current, uncontrolled renal, gastrointestinal, endocrine, pulmonary, cardiac, or neurologic disease History of malignancy within 10 years prior to screening, except for appropriately treated carcinoma in situ of the cervix or non-melanoma skin carcinoma History of alcohol, drug, or chemical abuse within 1 year prior to screening Laboratory exclusion criteria at screening including: estimated glomerular filtration rate (eGFR) <30ml/min Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >1.5 times upper limit of normal Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery during the study Immunization with a live/attenuated vaccine within 4 weeks prior to screening Pregnant or nursing women, or women of child bearing potential who plan to become pregnant prior to 14 weeks after the last dose of abatacept treatment Patients of reproductive potential not willing to use an effective method of contraception Prisoners, or subjects who are compulsory detained

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abatacept<br>Abatacept 125mg subcutaneous injection weekly for 24 weeks | Drug: Abatacept<br>* All the subjects will receive Abatacept subcutaneous injection once a week for 24 weeks<br>* Other names: Orencia;|

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 at Week 14 | Baseline levels of T cell-associated biomarkers predict ACR20 response (improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, pain, functional ability measure, erythrocyte sedimentation rate (ESR) or C-reactive protein) with subcutaneous abatacept | 14 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 Response at Week 24 | Baseline levels of T cell associated biomarkers predict ACR20 response (improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, pain, functional ability measure, erythrocyte sedimentation rate (ESR) or C-reactive protein) with subcutaneous abatacept | 24 Weeks | 
| ACR50 Response at Week 24 | Baseline levels of T cell associated biomarkers predict ACR50 response (improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, pain, functional ability measure, erythrocyte sedimentation rate (ESR) or C-reactive protein) with subcutaneous abatacept | Week 24 | 
| ACR70 Response at Week 24 | Baseline levels of T cell associated biomarkers predict ACR70 response (improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, pain, functional ability measure, erythrocyte sedimentation rate (ESR) or C-reactive protein) with subcutaneous abatacept | Week 24 | 
| European League Against Rheumatism (EULAR) good or moderate response at Week 24 | Baseline levels of T cell associated biomarkers predict EULAR good or moderate response (disease activity index for RA generated from tender and swollen joint count, patient global assessment, ESR or C-reactive protein) with subcutaneous abatacept | Week 24 |