A Phase IIIb, Multi-center, Stratified, Open-Label Study to Evaluate the Immunogenicity, Steady State Trough Level, and Safety of Subcutaneous Abatacept (BMS-188667) in Subjects With Rheumatoid Arthritis Administered With or Without Background Methotrexate
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 119
- 试验地点
- 16
- 主要终点
- Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (ELISA Method) Over Time During the ST Study
研究概览
简要总结
To evaluate safety and immunogenicity of abatacept when used with or without methotrexate in the absence of an IV loading dose of abatacept
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of Rheumatoid Arthritis
- •Subjects Global Disease Assessment of greater than equal to 20 mm on a visual analog scale
- •Discontinue all Biologics and Disease-modifying antirheumatic drugs (DMARDS) except for methotrexate
排除标准
- •Received treatment with rituximab
- •Subjects who have received treatment with immunoadsorbtion columns (such as Prosorba columns), mycophenolate mofetil (Cellcept®), cyclosporine A or other calcineurin inhibitors, or D-Penicillamine
研究组 & 干预措施
Subcutaneous (SC) Abatacept + Methotrexate (MTX) Cohort
In the ST period, participants were administered a dose of 125 mg abatacept SC, once weekly, for 4 months. Participants were also administered a stable MTX dose of greater than or equal to 10 mg once weekly for at least 4 weeks prior to first injection of SC abatacept.
干预措施: abatacept (Drug)
Subcutaneous (SC) Abatacept + Methotrexate (MTX) Cohort
In the ST period, participants were administered a dose of 125 mg abatacept SC, once weekly, for 4 months. Participants were also administered a stable MTX dose of greater than or equal to 10 mg once weekly for at least 4 weeks prior to first injection of SC abatacept.
干预措施: Methotrexate (MTX) (Drug)
SC Abatacept Monotherapy Cohort
In the ST period, participants were administered a dose of 125 mg abatacept SC, once weekly, for 4 months. Participants did not receive MTX at screening i.e., MTX naive, or discontinued MTX due to lack of efficacy or tolerability at least 4 weeks prior to first injection of SC abatacept.
干预措施: abatacept (Drug)
结局指标
主要结局
Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (ELISA Method) Over Time During the ST Study
时间窗: Day 15, 29, 43, 57, 85,113 and 28, 56, and 85 days post last dose.
ELISA is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum. For anti-abatacept antibody ELISA, a sample was considered seropositive if it had a titer of 400 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of \< 400. A sample was considered positive in CTLA4-T antibody ELISA if it had a titer of 25 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of \< 25.
Number of Participants With Positive Anti-abatacept Responses to Abatacept (Meso-Scale Discovery [MSD] Electrochemiluminescence [ECL] Assay Method) Over Time During the ST Study
时间窗: Day 15, 29, 43, 57, 85,113 and 28, 56 and 85 days post last dose.
The ECL (MSD) assay method is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum. It is more sensitive and has a higher drug tolerance than ELISA method. For the anti-abatacept antibody ECL (MSD) assay, a sample was considered seropositive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept, or abatacept and CTLA4-T. Those responses that were not positive in the initial screen or were not confirmed to be positive based on immunodepletion were reported as seronegative and were assigned a value of \< 10.
Cross Tabulations of the Number of Participants With Positive and Negative Immunogenicity Status at Baseline and Each Visit During the ST Study (for MSD Results)
时间窗: Baseline and day 15, 29, 43, 57, 85 and 113.
The ECL (MSD) assay method is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum . It is more sensitive and has a higher drug tolerance than the ELISA method. For anti-abatacept antibody ECL(MSD) assay, a sample was considered seropositive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept, or abatacept and CTLA4-T. Those responses that were not positive in the initial screen or were not confirmed to be positive based on immunodepletion were reported as seronegative and were assigned a value of \< 10.
Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (Enzyme-linked Immunosorbent Assay [ELISA] Method) at Day 113 of the ST Study
时间窗: Day 113
ELISA is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum. For anti-abatacept antibody ELISA, a sample was considered seropositive if it had a titer of 400 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of \< 400. A sample was considered positive in CTLA4-T antibody ELISA if it had a titer of 25 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of \< 25.
Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for MSD Results)
时间窗: Day 113.
The ECL (MSD) assay method is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum. It is more sensitive and has a higher drug tolerance than the ELISA method. For anti-abatacept antibody ECL (MSD) assay, a sample was considered seropositive if it had a titer of 10 or greater and if immunodepletion was observed with abatacept, or abatacept and CTLA4-T. Those responses that were not positive in the initial screen or were not confirmed to be positive based on immunodepletion were reported as seronegative and were assigned a value of \< 10.
Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for ELISA Results)
时间窗: Day 113.
ELISA is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum. For anti-abatacept antibody ELISA, a sample was considered seropositive if it had a titer of 400 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of \< 400. A sample was considered positive in CTLA4-T antibody ELISA if it had a titer of 25 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of \< 25.
Cross Tabulations of the Number of Participants With Positive and Negative Immunogenicity Status at Baseline and Each Visit During the ST Study (for ELISA Results)
时间窗: Baseline and on day 15, 29, 43, 57, 85 and 113
ELISA is a validated, sensitive assay technique used to analyze presence of abatacept-specific antibodies in serum. For anti-abatacept antibody ELISA, a sample was considered seropositive if it had a titer of 400 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of \< 400. A sample was considered positive in CTLA4-T antibody ELISA if it had a titer of 25 or greater and if immunodepletion was observed. The responses that were negative in initial screen were reported as seronegative with a value of \< 25.
次要结局
- Change From Baseline in DAS28-CRP Score at End of 4-month (Day 113) of the ST Study(Baseline and Month 4 (Day113).)
- Cross Tabulations of Number of Participants With Positive and Negative Status for RF at Day 113 With Baseline, in the ST Study(Baseline and Day 113.)
- Number of Participants With Clinically Meaningful Improvement at End of 4-month (Day 113) of the ST Study(Day 113.)
- Change From Baseline in Physical Functioning (HAQ-DI) at End of the 4-month Treatment Period (Day 113) of the ST Study(Baseline and Month 4 (Day 113).)
- Number of Participants With MAs in Serum Chemistry During the ST Study: Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Bilirubin (Total), G-Glutamyl Transferase (G-GT) and Blood Urea Nitrogen (BUN)(Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.)
- Number of Participants With MAs in Urinalysis During the ST Study: Protein, Glucose, Blood, Leukocyte Esterase, Red Blood Cells (RBC) and White Blood Cells (WBC)(Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.)
- Number of Participants With Anti-double Stranded DNA (dsDNA) Category at Day 113 of the ST Study(Day 113.)
- Number of Participants in DAS28-CRP Remission and Number of Participants With Low Disease Activity (LDA) in the LTE Study - All Treated Participants in the LTE(Day 113, Day 1345)
- Number of Participants With AEs of Special Interest During the ST Study(Continuously through ST period (up to Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.)
- Number of Participants With Anti-nuclear Antibody (ANA) Category at Day 113 of the ST Study(Day 113.)
- Number of Participants With Clinically Meaningful Vital Signs During the ST Study(At screening and on days 1,15,29,43, 57, 85 and 113.)
- Change From Baseline in DAS28-CRP Score and Physical Function (HAQ-DI) Score in the LTE Study - Abatacept Monotherapy Subgroup(Baseline, Day 113, Day 1345)
- Change From Baseline in All HAQ-DI Components at End of the 4-month Treatment Period (Day 113) of the ST Study(Baseline and Month 4 (Day113).)
- Number of Participants With Marked Abnormalities (MAs) in Hematology During the ST Study: Hemoglobin, Hematocrit, Platelet Count, Erythrocytes and Leukocytes(Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.)
- Minimum Plasma Concentration (Cmin) at Each Visit During the 4 Month Treatment Period of the ST Study(Days 1, 15, 29, 43, 57, 85 and 113.)
- Number of Participants With Clinically Meaningful Improvement From Baseline in the LTE Study - All Treated Participants in LTE Study(Baseline, Day 113, Day 1345)
- Number of Participants With AEs of Special Interest During the LTE Study - All Treated Participants in LTE Study(Continuously from start of LTE Study up to 56 days post the last dose)
- Number of Participants Who Experienced Drug-related SAEs and Drug-related AEs During the ST Study(Continuously through ST period (upto Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.)
- Number of Participants With MAs in Hematology During the ST Study: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)(Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.)
- Number of Participants With MAs in Serum Chemistry During the ST Study: Creatinine, Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total) and Protein (Total)(Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.)
- Change From Baseline in DAS28-CRP Score in the LTE Study - All Treated Participants in LTE Study(Baseline, Day 113, Day 1345)
- Number of Participants With Negative Status for RF up to 7 Days After Last Dose of Abatacept in the LTE Period - All Treated Participants in LTE Study(Continuously from start of LTE period up to 7 days post the last dose)
- Number of Participants Who Died, Experienced SAEs, Experienced AEs or Who Discontinued Due to AEs During the ST Study(Continuously through ST period (upto Day 113). Includes the data from start of study drug therapy up to 56 days after the last dose (Day 113) or start of the long-term period whichever occurred first.)
- Number of Participants With MAs in Serum Chemistry During the ST Study: Glucose (Fasting Serum), Albumin, Glucose (Serum), Phosphorous (Inorganic) and Uric Acid(Continuously from start of ST period up to 56 days post the last dose in the short-term period or start of the long-term period, whichever occurred first.)
- Number of Participants With Abatacept Induced Antibody Responses Over Time During the LTE Study (ECL Method) - All Treated Participants in LTE Study(Days 197, 281, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541, 1625, 1709, 1821, 1989, days post dose: 28, 56, 85, 168)
- Change From Baseline in HAQ-DI in the LTE Study - All Treated Participants in LTE Study(Baseline, Day 113, Day 1345)
- Number of Participants With MAs in Serum Chemistry (Electrolytes, Glucose, Protein, and Metabolite) During the LTE Period - All Treated Participants in LTE Study(Continuously from start of LTE Study up to 56 days post the last dose)
- Number of Participants With HAQ Responses in the LTE Study - All Treated Participants in the LTE STudy(Baseline, Day 113, Day 1345)
- Number of Participants With Marked Abnormalities (MAs) in Hematology During the LTE Period - All Treated Participants in LTE Study(Continuously from start of LTE Study up to 56 days post the last dose)
- Number of Participants With MAs in Serum Chemistry (Liver and Kidney Function) During the LTE Period - All Treated Participants in LTE Study(Continuously from start of LTE Study up to 56 days post the last dose)
- Number of Participants in DAS 28-CRP Remission and Low Disease Activity (LDA) in the LTE Study - Abatacept Monotherapy Subgroup(Day 113, Day 1345)
- Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs), or Discontinued Due to AEs and/or SAEs During the LTE Period - All Treated Participants in LTE Study(Continuously from start of LTE Study up to 56 days post the last dose)
- Number of Participants With MAs in Urinalysis During the LTE Period: Protein, Glucose, Blood, Leukocyte Esterase, Red Blood Cells (RBC) and White Blood Cells (WBC) - All Treated Participants in LTE Study(Continuously from start of LTE Study up to 56 days post the last dose)