World Health Organization site
Skip Navigation Links

Main
Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 19 October 2017
Main ID:  NCT00533897
Date of registration: 20/09/2007
Prospective Registration: Yes
Primary sponsor: Bristol-Myers Squibb
Public title: Phase IIIB Subcutaneous Missed Dose Study
Scientific title: A Phase IIIb, Multi-Center, Randomized, Withdrawal Study to Evaluate the Immunogenicity and Safety of Subcutaneous Administered Abatacept in Adults With Active Rheumatoid Arthritis
Date of first enrolment: November 2007
Target sample size: 270
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT00533897
Study type:  Interventional
Study design:   
Phase:  Phase 3
Countries of recruitment
Argentina Brazil Canada Mexico South Africa United States
Contacts
Name:     Bristol-Myers Squibb
Address: 
Telephone:
Email:
Affiliation:  Bristol-Myers Squibb
Key inclusion & exclusion criteria

Inclusion Criteria:

- Clinical diagnosis of Rheumatoid Arthritis

- Disease Activity Score (DAS)28-C-Reactive Protein (CRP) score = 3.2 and =5.1

- On background methotrexate at least 3 months (=10mg weekly)

- Must be able to self injection or allow a care giver to do it for them

- Discontinue all Biologics and Disease-Modifying Anti-rheumatic Drugs (DMARDs) except
for methotrexate

Exclusion Criteria:

- Participants who had prior exposure to abatacept or CTLA-4 Ig

- Received treatment with rituximab.

- Participants who have received treatment with leflunomide within 1 year of screening

- Participants who have received treatment with immunoadsorption columns (such as
Prosorba columns), mycophenolate mofetil (CellceptĀ®), cyclosporine A or other
calcineurin inhibitors, or D-Penicillamine.



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Rheumatoid Arthritis
Intervention(s)
Drug: Abatacept
Drug: Placebo
Primary Outcome(s)
Double-blind Withdrawal (DBW) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Antibody Responses by Enzyme-Linked Immunosorbent Assay (ELISA) at Day 169 [Time Frame: Day 169]
Re-introduction (RI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Groups [Time Frame: Day 253 (short term)]
Secondary Outcome(s)
DBW Period; Mean Change in DAS 28 (CRP) From DBW Period Baseline (Day 85) Over Time [Time Frame: Days 85 (Period 2 Baseline), 113, 141, and 169]
DBW Period; Mean Heart Rate (HR) During Period 2 [Time Frame: Days 113, 141, and 169]
DBW Period; Mean Temperature (T) During Period II [Time Frame: Days 113, 141, and 169]
DBW Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL At Post Visits [Time Frame: 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 [Time Frame: 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 ELISA at Post Visits [Time Frame: 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 [Time Frame: Days 86-169, includes =21 Days after last dose or up to 1st dose of RI Period]
DBW Period; Percentage of Participants With Rheumatoid Arthritis (RA) Flare Over Time [Time Frame: Days 85, 113, 141, and 169]
DBW; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Double Blind Period [Time Frame: Days 113, 141, and 169]
DBW; Number of Participants With AEs of Special Interest [Time Frame: 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 Death, Serious SAEs, Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation [Time Frame: 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 [Time Frame: 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 [Time Frame: 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 Liver and Kidney Function Values Meeting the Marked Abnormality Criteria [Time Frame: 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 Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria [Time Frame: 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]
Lead-in (LI) Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time [Time Frame: 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]
LI Period; Mean Heart Rate (HR) [Time Frame: Days 1, 15, 29, 57, 78, and 85]
LI Period; Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Time Frame: Days 1, 15, 29, 57, 78, and 85]
LI Period; Mean Temperature (T) [Time Frame: Days 1, 15, 29, 57, 78, and 85]
LI Period; Number of Participants With AEs of Special Interest [Time Frame: 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; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by Electrochemiluminescence (ECL) Over Time [Time Frame: 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]
LI; Mean Change in DAS 28 (CRP) From Baseline Over Time [Time Frame: Days 1 (Baseline), 15, 29, 57, 78, 85]
LI; Number of Participants With Deaths, Serious Adverse Events (SAEs), SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation [Time Frame: 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 Electrolyte Values Meeting the Marked Abnormality Criteria [Time Frame: 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 Hematology Values Meeting the Marked Abnormality (MA) Criteria [Time Frame: 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 [Time Frame: 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 [Time Frame: 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; Percentage of Participants With Clinically Meaningful Improvement in DAS (CRP) Over Time [Time Frame: Days 15, 29, 57, 78, 85]
LTE: DAS28-CRP Mean Change From Baseline (Day 1) Over Time - All Participants Treated in LTE [Time Frame: 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: Mean Heart Rate (HR) During LTE [Time Frame: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073]
LTE: Mean Seated Diastolic Blood Pressure (DBP) During LTE [Time Frame: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261, 1345, 1457,1541,1625,1709,1821,1905,1989,2073]
LTE: Mean Seated Systolic Blood Pressure (SBP) During LTE [Time Frame: Days 337, 365, 449, 533, 617, 729,813, 897,981, 1093, 1177,1261,1345, 1457,1541,1625,1709,1821,1905,1989,2073]
LTE: Mean Temperature (T) During LTE [Time Frame: 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 AEs of Special Interest During LTE [Time Frame: 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 Death, Related SAEs, SAEs Leading to Discontinuation, Related AEs, or AEs Leading to Discontinuation During Long Term Extension (LTE) [Time Frame: 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 Electrolyte Values Meeting the Marked Abnormality Criteria During LTE [Time Frame: 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: Number of Participants With Hematology Values Meeting the Marked Abnormality Criteria During LTE [Time Frame: 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: Number of Participants With Liver and Kidney Function Values Meeting the Marked Abnormality Criteria During LTE [Time Frame: 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: Number of Participants With Other Chemistry and Urinalysis Values Meeting the Marked Abnormality Criteria During LTE [Time Frame: 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: 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 [Time Frame: 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: Percent of Participants Who Achieved Clinical Remission in the Long Term Extension - All Participants Treated in LTE [Time Frame: 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: Percent of Participants With HAQ Response Over Time - All Participants Treated in LTE [Time Frame: 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: Percent of Participants With Low Disease Activity in Long Term Extension: All Participants Treated in LTE [Time Frame: 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.]
RI Period; Mean Change in DAS 28 (CRP) From RI Period Baseline (Day 169) Over Time [Time Frame: Days 169 (Period III Baseline), 197, 225, and 253]
RI Period; Mean Heart Rate (HR) During Period III [Time Frame: Days 169, 197, 225, and 253]
RI Period; Mean Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During Period III [Time Frame: Days 169, 197, 225, and 253]
RI Period; Mean Temperature (T) During Period III [Time Frame: Days 169, 197, 225, and 253]
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ECL Over Time by DBW Treatment Group [Time Frame: 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]
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA at Day 253, by DBW Period Placebo Group [Time Frame: Day 253 (short term)]
RI Period; Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 Antibody Responses by ELISA Over Time by DBW Treatment Group [Time Frame: 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]
RI; Number of Participants With AEs of Special Interest [Time Frame: 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 Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation [Time Frame: 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 Electrolytes Values Meeting the Marked Abnormality Criteria [Time Frame: 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 [Time Frame: 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 Liver and Kidney Function Values Meeting the Marked Abnormality Criteria [Time Frame: 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 [Time Frame: 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 (ST); Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ELISA Antibody Responses by DBW Treatment Groups [Time Frame: 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: Mean Change in Disease Activity Score (DAS) 28 (Using C-Reactive Protein [CRP]) From Baseline Over Time by DBW Treatment Groups [Time Frame: 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 [Time Frame: Days 85, 169, and 253 (short term)]
Short Term: Percentage of Participants With Positive Anti-Abatacept or Anti-CTLA4 ECL Antibody Responses by DBW Treatment Groups [Time Frame: 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; Abatacept Serum Concentration by Immunogenicity Status as Measured by ECL by RI Treatment Groups [Time Frame: Day 197 through Day 253]
Short Term; Abatacept Serum Concentration by Immunogenicity Status as Measured by ELISA by RI Treatment Groups [Time Frame: Day 197 through Day 253]
Short Term; Mean Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) From Baseline Over Time by DBW Treatment Groups [Time Frame: Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)]
Short Term; Percentage of Participants With HAQ-DI Response Over Time by DBW Treatment Groups [Time Frame: Days 1 (Baseline),15, 29, 57, 78, 85, 113, 141, 169, 197, 225, and 253 (short term)]
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 [Time Frame: Baseline, Day 253]
Secondary ID(s)
IM101-167
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available: Yes
Date Posted: 03/06/2011
Date Completed:
URL: https://clinicaltrials.gov/ct2/show/results/NCT00533897
Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.
Copyright - World Health Organization - Version 3.6 - Version history