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

Phase 4

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: Abatacept

Registration Number: NCT03882008

Lead Sponsor: University of Washington

Brief Summary: 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)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

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:
1. estimated glomerular filtration rate (eGFR) <30ml/min
2. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Abatacept	Abatacept	Abatacept 125mg subcutaneous injection weekly for 24 weeks

Primary Outcome Measures

Name	Time	Method
Number of Participants With American College of Rheumatology (ACR) 20 Response at Week 14	14 Weeks	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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With American College of Rheumatology (ACR) 70 Response at Week 24	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
Number of Participants With American College of Rheumatology (ACR) 20 Response at Week 24	24 Weeks	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
Number of Participants With American College of Rheumatology (ACR) 50 Response at Week 24	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
Number of Participants With European League Against Rheumatism (EULAR) Good or Moderate Response at Week 24	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