Rheumatoid Arthritis
Conditions
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)
Interventions
DRUGAbatacept
All the subjects will receive Abatacept subcutaneous injection once a week for 24 weeks
Sponsors
Bristol-Myers Squibb
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abatacept Subjects will receive abatacept 125mg subcutaneous injection once a week for 24 doses (24 weeks) | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Abatacept |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 8 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Number of Participants With 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
Time frame: 14 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Number of Participants With American College of Rheumatology (ACR) 20 Response at Week 14 | 9 participants |
Secondary
Number of Participants With American College of Rheumatology (ACR) 20 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
Time frame: 24 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Number of Participants With American College of Rheumatology (ACR) 20 Response at Week 24 | 14 participants |
Secondary
Number of Participants With American College of Rheumatology (ACR) 50 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
Time frame: Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Number of Participants With American College of Rheumatology (ACR) 50 Response at Week 24 | 10 participants |
Secondary
Number of Participants With American College of Rheumatology (ACR) 70 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
Time frame: Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Number of Participants With American College of Rheumatology (ACR) 70 Response at Week 24 | 3 participants |
Secondary
Number of Participants With 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
Time frame: Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abatacept | Number of Participants With European League Against Rheumatism (EULAR) Good or Moderate Response at Week 24 | 17 participants |