A Phase IIIb, Multi-Center, Randomized, Withdrawal Study to Evaluate the Immunogenicity and Safety of Subcutaneous Administered Abatacept in Adults With Active Rheumatoid Arthritis

简要总结

主要结局

次要结局

• Lead-in (LI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time(For on-treatment visits: Day 1-Day 85, includes ≤21 Days after last dose or up to 1st dose of DBW Period. For follow-up post visits for participants who discontinued drug in LI: Day 22 after last dose of drug to Day 85 after last dose of drug)
• DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time(Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period)
• DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL At Post Visits(Day 22 after last dose of drug to Day 85 after last dose of drug)
• RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time by DBW Treatment Group(For on-treatment visits: Days 170-253, includes ≤21 Days after last dose or up to 1st dose of LTE Period. For follow-up post visits for participants who discontinued drug in RI: Day 22 after last dose of drug to Day 85 after last dose of drug)
• Short Term (ST); Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ELISA Antibody Responses by DBW Treatment Groups(For on-TRT visits: Days 1-253 (ST). For follow-up post visits for participants who discontinued drug in the ST: Day 22 after last dose of ST drug to Day 85 after last dose of ST drug)
• Short Term: Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ECL Antibody Responses by DBW Treatment Groups(For on-TRT visits: Days 1-253 (ST). For follow-up post visits for participants who discontinued drug in the ST: Day 22 after last dose of ST drug to Day 85 after last dose of ST drug)
• LI; Mean Change in DAS 28 (CRP) From Baseline Over Time(Days 1 (Baseline), 15, 29, 57, 78, 85)
• LI; Percentage of Participants With Clinically Meaningful Improvement in DAS (CRP) Over Time(Days 15, 29, 57, 78, 85)
• LI Period; Number of Participants With AEs of Special Interest(From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier)
• RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Placebo Group(Day 253 (short term))
• DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Post Visits(Day 22 after last dose of drug to Day 85 after last dose of drug)
• DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time(Days 86-169, includes ≤21 Days after last dose or up to 1st dose of RI Period)
• Short Term; Mean Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline Over Time by DBW Treatment Groups(Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term))
• RI Period; Mean Change in DAS 28 (CRP) From RI Period Baseline (Day 169) Over Time(Days 169 (Period III Baseline), 197, 225, and 253)
• LI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by Electrochemiluminescence (ECL) Over Time(For on-treatment visits: Day 1-Day 85, includes ≤21 Days after last dose or up to 1st dose of DBW Period. For follow-up post visits for participants who discontinued drug in LI: Day 22 after last dose of drug to Day 85 after last dose of drug)
• RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time by DBW Treatment Group(For on-treatment visits: Days 170-253, includes ≤21 Days after last dose or up to 1st dose of LTE Period. For follow-up post visits for participants who discontinued drug in RI: Day 22 after last dose of drug to Day 85 after last dose of drug)
• DBW; Number of Participants With AEs of Special Interest(From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier)
• DBW; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria(From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier)
• Short Term: Mean Change in Disease Activity Score (DAS) 28 (Using C-Reactive Protein [CRP]) From Baseline Over Time by DBW Treatment Groups(Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term))
• Short Term: Percentage of Participants Achieving Clinically Meaningful Improvement (CMI) in DAS 28 (CRP), Low Disease Activity (LDAS), or Clinical Remission Over Time by DBW Treatment Groups(Days 85, 169, and 253 (short term))
• Short Term; Percentage of Participants With HAQ-DI Response Over Time by DBW Treatment Groups(Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term))
• DBW Period; Percentage of Participants With Rheumatoid Arthritis (RA) Flare Over Time(Days 85, 113, 141, and 169)
• LI; Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria(From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier)
• LI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria(From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier)
• LI Period; Mean Heart Rate (HR)(Days 1, 15, 29, 57, 78, and 85)
• DBW Period; Mean Change in DAS 28 (CRP) From DBW Period Baseline (Day 85) Over Time(Days 85 (Period 2 Baseline), 113, 141, and 169)
• LI; Number of Participants With Deaths, Serious Adverse Events (SAEs), SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation(From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier)
• LI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria(From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier)
• LI Period; Mean Temperature (T)(Days 1, 15, 29, 57, 78, and 85)
• DBW; Number of Participants With Death, Serious SAEs, Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation(From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier)
• DBW; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Double Blind Period(Days 113, 141, and 169)
• DBW Period; Mean Heart Rate (HR) During Period 2(Days 113, 141, and 169)
• DBW Period; Mean Temperature (T) During Period II(Days 113, 141, and 169)
• RI; Number of Participants With AEs of Special Interest(From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.)
• RI; Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria(From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.)
• LI; Number of Participants With Hematology Values Meeting the Marked Abnormality (MA) Criteria(From Day 1 through Day 85, up to 56 days post last dose in Lead-in Period or up to first dose in next period, whichever occurred earlier)
• LI Period; Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Days 1, 15, 29, 57, 78, and 85)
• RI; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria(From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.)
• LTE: Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria During LTE(For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.)
• DBW; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria(From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier)
• RI; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria(From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.)
• RI; Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria(From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.)
• Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ECL by RI Treatment Groups(Day 197 through Day 253)
• ST; Number of Participants Positive for Anti-nuclear Antibody (ANA), Anti-double Stranded DNA Antibody (dsDNA), or Rheumatoid Factor (RF) at Day 253 According to Baseline Status (Negative at Baseline or Positive at Baseline) by DBW Treatment Groups(Baseline, Day 253)
• DBW; Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria(From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier)
• DBW; Number of Participants With Electrolytes Values Meeting the Marked Abnormality Criteria(From Day 85 through Day 169, up to 56 days post last dose in DBW Period or up to first dose in RI Period, whichever occurred earlier)
• RI; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation(From Day 169 through Day 253, up to 56 days post last dose in RI Period or up to first dose in LTE, whichever occurred earlier.)
• RI Period; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Period III(Days 169, 197, 225, and 253)
• RI Period; Mean Heart Rate (HR) During Period III(Days 169, 197, 225, and 253)
• RI Period; Mean Temperature (T) During Period III(Days 169, 197, 225, and 253)
• LTE: DAS28-CRP Mean Change From Baseline (Day 1) Over Time - All Participants Treated in LTE(For Period 1 non-responders: as of Study Day 85 and up to Day 1821. For ST completers: as of Study Day 253 and up to Day 1821.)
• LTE: Percent of Participants Who Achieved Clinical Remission in the Long Term Extension - All Participants Treated in LTE(For Period I non-responders: as of Study Day 85 and up to Study Day 1821. For ST completers: as of Study Day 253 and up to Study Day 1821)
• LTE: Number of Participants With Death, Related SAEs, SAEs Leading to Discontinuation, Related AEs, or AEs Leading to Discontinuation During Long Term Extension (LTE)(For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014), up to 56 days post last dose. For ST completers: as of Day 253 and up to completion of LTE (FEB 2014) up to 56 days post last dose.)
• LTE: Number of Participants With AEs of Special Interest During LTE(For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014) up to 56 days post last dose. For ST completers: as of Day 253 and up to completion of LTE (FEB 2014) up to 56 days post last dose.)
• LTE: Mean Seated Systolic Blood Pressure (SBP) During LTE(Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261,1345, 1457,1541,1625,1709,1821,1905,1989,2073)
• Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ELISA by RI Treatment Groups(Day 197 through Day 253)
• LTE: Percent of Participants With Low Disease Activity in Long Term Extension: All Participants Treated in LTE(For Period 1 non-responders: as of Study Day 85 and up to Day 1821. For ST completers: as of Study Day 253 and up to Day 1821.)
• LTE: Percent of Participants With HAQ Response Over Time - All Participants Treated in LTE(Study Days 1 (Baseline),15, 29, 57, 78, 85, 253, 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1345, 1457, 1541,1625,1709,1821,1905,1989, 2073)
• LTE: Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria During LTE(For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.)
• LTE: Mean Heart Rate (HR) During LTE(Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073)
• LTE: Overall Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses (ECL Method) for On-Treatment Visits, Post Last Dose Visits, and Overall Study - All Participants Treated in LTE(Days 337, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1177, 1261, 1457, 1625, 1821, 1989 and 28, 56, 85, 168 days post last dose in LTE)
• LTE: Number of Participants With Electrolyte Values Meeting the Marked Abnormality Criteria During LTE(For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.)
• LTE: Mean Seated Diastolic Blood Pressure (DBP) During LTE(Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073)
• LTE: Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria During LTE(For Period I non-responders: as of Day 85 and up to completion of LTE (FEB 2014). For ST completers: as of Day 253 and up to completion of LTE (FEB 2014). Data included up to 56 days post last dose.)
• LTE: Mean Temperature (T) During LTE(Days 337, 365, 449,533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073)