Clinical trial NCT00547521: Phase IIIB Subcutaneous Abatacept Monotherapy Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis (RA)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-10-22
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate safety and immunogenicity of abatacept when used with or without methotrexate in the absence of an IV loading dose of abatacept


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (Enzyme-linked Immunosorbent Assay [ELISA] Method) at Day 113 of the ST Study
timeFrame: Day 113
measure: Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (ELISA Method) Over Time During the ST Study
timeFrame: Day 15, 29, 43, 57, 85,113 and 28, 56, and 85 days post last dose.
measure: Number of Participants With Positive Anti-abatacept Responses to Abatacept (Meso-Scale Discovery [MSD] Electrochemiluminescence [ECL] Assay Method) Over Time During the ST Study
timeFrame: Day 15, 29, 43, 57, 85,113 and 28, 56 and 85 days post last dose.
measure: Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for ELISA Results)
timeFrame: Day 113.
measure: Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for MSD Results)
timeFrame: Day 113.
measure: 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)
timeFrame: Baseline and on day 15, 29, 43, 57, 85 and 113
measure: 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)
timeFrame: Baseline and day 15, 29, 43, 57, 85 and 113.
Secondary outcomes:
measure: Change From Baseline in DAS28-CRP Score at End of 4-month (Day 113) of the ST Study
timeFrame: Baseline and Month 4 (Day113).
measure: Number of Participants With Clinically Meaningful Improvement at End of 4-month (Day 113) of the ST Study
timeFrame: Day 113.
measure: Change From Baseline in Physical Functioning (HAQ-DI) at End of the 4-month Treatment Period (Day 113) of the ST Study
timeFrame: Baseline and Month 4 (Day 113).
measure: Change From Baseline in All HAQ-DI Components at End of the 4-month Treatment Period (Day 113) of the ST Study
timeFrame: Baseline and Month 4 (Day113).
measure: Cross Tabulations of Number of Participants With Positive and Negative Status for RF at Day 113 With Baseline, in the ST Study
timeFrame: Baseline and Day 113.
measure: Number of Participants Who Died, Experienced SAEs, Experienced AEs or Who Discontinued Due to AEs During the ST Study
timeFrame: 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.
measure: Number of Participants Who Experienced Drug-related SAEs and Drug-related AEs During the ST Study
timeFrame: 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.
measure: Number of Participants With AEs of Special Interest During the ST Study
timeFrame: 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.
measure: Number of Participants With Marked Abnormalities (MAs) in Hematology During the ST Study: Hemoglobin, Hematocrit, Platelet Count, Erythrocytes and Leukocytes
timeFrame: 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.
measure: Number of Participants With MAs in Hematology During the ST Study: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
timeFrame: 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.
measure: 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)
timeFrame: 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.
measure: Number of Participants With MAs in Serum Chemistry During the ST Study: Creatinine, Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total) and Protein (Total)
timeFrame: 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.
measure: Number of Participants With MAs in Serum Chemistry During the ST Study: Glucose (Fasting Serum), Albumin, Glucose (Serum), Phosphorous (Inorganic) and Uric Acid
timeFrame: 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.
measure: 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)
timeFrame: 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.
measure: Number of Participants With Anti-nuclear Antibody (ANA) Category at Day 113 of the ST Study
timeFrame: Day 113.
measure: Number of Participants With Anti-double Stranded DNA (dsDNA) Category at Day 113 of the ST Study
timeFrame: Day 113.
measure: Number of Participants With Clinically Meaningful Vital Signs During the ST Study
timeFrame: At screening and on days 1,15,29,43, 57, 85 and 113.
measure: Minimum Plasma Concentration (Cmin) at Each Visit During the 4 Month Treatment Period of the ST Study
timeFrame: Days 1, 15, 29, 43, 57, 85 and 113.
measure: Number of Participants With Abatacept Induced Antibody Responses Over Time During the LTE Study (ECL Method) - All Treated Participants in LTE Study
timeFrame: 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
measure: Change From Baseline in DAS28-CRP Score in the LTE Study - All Treated Participants in LTE Study
timeFrame: Baseline, Day 113, Day 1345
measure: Number of Participants With Clinically Meaningful Improvement From Baseline in the LTE Study - All Treated Participants in LTE Study
timeFrame: Baseline, Day 113, Day 1345
measure: 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
timeFrame: Day 113, Day 1345
measure: Change From Baseline in HAQ-DI in the LTE Study - All Treated Participants in LTE Study
timeFrame: Baseline, Day 113, Day 1345
measure: Number of Participants With HAQ Responses in the LTE Study - All Treated Participants in the LTE STudy
timeFrame: Baseline, Day 113, Day 1345
measure: 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
timeFrame: Continuously from start of LTE period up to 7 days post the last dose
measure: Change From Baseline in DAS28-CRP Score and Physical Function (HAQ-DI) Score in the LTE Study - Abatacept Monotherapy Subgroup
timeFrame: Baseline, Day 113, Day 1345
measure: Number of Participants in DAS 28-CRP Remission and Low Disease Activity (LDA) in the LTE Study - Abatacept Monotherapy Subgroup
timeFrame: Day 113, Day 1345
measure: 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
timeFrame: Continuously from start of LTE Study up to 56 days post the last dose
measure: Number of Participants With AEs of Special Interest During the LTE Study - All Treated Participants in LTE Study
timeFrame: Continuously from start of LTE Study up to 56 days post the last dose
measure: Number of Participants With Marked Abnormalities (MAs) in Hematology During the LTE Period - All Treated Participants in LTE Study
timeFrame: Continuously from start of LTE Study up to 56 days post the last dose
measure: Number of Participants With MAs in Serum Chemistry (Liver and Kidney Function) During the LTE Period - All Treated Participants in LTE Study
timeFrame: Continuously from start of LTE Study up to 56 days post the last dose
measure: Number of Participants With MAs in Serum Chemistry (Electrolytes, Glucose, Protein, and Metabolite) During the LTE Period - All Treated Participants in LTE Study
timeFrame: Continuously from start of LTE Study up to 56 days post the last dose
measure: 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
timeFrame: Continuously from start of LTE Study up to 56 days post the last dose
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rheumatology Associates Of North Alabama
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research Inc
state: Alabama
city: Palo Alto
country: United States
facility: Stanford University School Of Medicine
state: California
city: Boulder
country: United States
facility: Boulder Medical Center
state: Colorado
city: Palm Harbor
country: United States
facility: The Arthritis Center
state: Florida
city: Louisville
country: United States
facility: Medical Towers South
state: Kentucky
city: Omaha
country: United States
facility: Westroads Medical Group
state: Nebraska
city: Binghamton
country: United States
facility: Regional Rheumatology Associates
state: New York
city: Greenville
country: United States
facility: Physicians East, Pa
state: North Carolina
city: Tulsa
country: United States
facility: Healthcare Research Consultants
state: Oklahoma
city: Bethlehem
country: United States
facility: East Penn Rheumatology Associates
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research
state: Pennsylvania
city: Charleston
country: United States
facility: Low Country Rheumatology, Pa
state: South Carolina
city: Columbia
country: United States
facility: Columbia Arthritis Center
state: South Carolina
city: Glendale
country: United States
facility: Rheumatic Disease Center
state: Wisconsin
city: Maroochydore
country: Australia
facility: Local Institution
state: Queensland
city: Hobart
country: Australia
facility: Local Institution
state: Tasmania
city: Malvern
country: Australia
facility: Local Institution
state: Victoria
city: D.f.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Berea
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Panorama
country: South Africa
facility: Local Institution
state: Western Cape
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Nash P, Nayiager S, Genovese MC, Kivitz AJ, Oelke K, Ludivico C, Palmer W, Rodriguez C, Delaet I, Elegbe A, Corbo M. Immunogenicity, safety, and efficacy of abatacept administered subcutaneously with or without background methotrexate in patients with rheumatoid arthritis: results from a phase III, international, multicenter, parallel-arm, open-label study. Arthritis Care Res (Hoboken). 2013 May;65(5):718-28. doi: 10.1002/acr.21876.