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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00547521




Registration number
NCT00547521
Ethics application status
Date submitted
19/10/2007
Date registered
22/10/2007
Date last updated
23/03/2015

Titles & IDs
Public title
Phase IIIB Subcutaneous Abatacept Monotherapy Study
Scientific 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
Secondary ID [1] 0 0
IM101-173
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis (RA) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - abatacept
Treatment: Drugs - Methotrexate (MTX)

Experimental: 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.

Experimental: 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.


Treatment: Drugs: abatacept
solution, subcutaneous injection, 125 mg/kg, weekly, 106 days in short term; long term is open

Treatment: Drugs: Methotrexate (MTX)
Participants who were currently receiving methotrexate at a stable dose = 10 mg for at least 4 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (Enzyme-linked Immunosorbent Assay [ELISA] Method) at Day 113 of the ST Study
Timepoint [1] 0 0
Day 113
Primary outcome [2] 0 0
Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (ELISA Method) Over Time During the ST Study
Timepoint [2] 0 0
Day 15, 29, 43, 57, 85,113 and 28, 56, and 85 days post last dose.
Primary outcome [3] 0 0
Number of Participants With Positive Anti-abatacept Responses to Abatacept (Meso-Scale Discovery [MSD] Electrochemiluminescence [ECL] Assay Method) Over Time During the ST Study
Timepoint [3] 0 0
Day 15, 29, 43, 57, 85,113 and 28, 56 and 85 days post last dose.
Primary outcome [4] 0 0
Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for ELISA Results)
Timepoint [4] 0 0
Day 113.
Primary outcome [5] 0 0
Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for MSD Results)
Timepoint [5] 0 0
Day 113.
Primary outcome [6] 0 0
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)
Timepoint [6] 0 0
Baseline and on day 15, 29, 43, 57, 85 and 113
Primary outcome [7] 0 0
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)
Timepoint [7] 0 0
Baseline and day 15, 29, 43, 57, 85 and 113.
Secondary outcome [1] 0 0
Change From Baseline in DAS28-CRP Score at End of 4-month (Day 113) of the ST Study
Timepoint [1] 0 0
Baseline and Month 4 (Day113).
Secondary outcome [2] 0 0
Number of Participants With Clinically Meaningful Improvement at End of 4-month (Day 113) of the ST Study
Timepoint [2] 0 0
Day 113.
Secondary outcome [3] 0 0
Change From Baseline in Physical Functioning (HAQ-DI) at End of the 4-month Treatment Period (Day 113) of the ST Study
Timepoint [3] 0 0
Baseline and Month 4 (Day 113).
Secondary outcome [4] 0 0
Change From Baseline in All HAQ-DI Components at End of the 4-month Treatment Period (Day 113) of the ST Study
Timepoint [4] 0 0
Baseline and Month 4 (Day113).
Secondary outcome [5] 0 0
Cross Tabulations of Number of Participants With Positive and Negative Status for RF at Day 113 With Baseline, in the ST Study
Timepoint [5] 0 0
Baseline and Day 113.
Secondary outcome [6] 0 0
Number of Participants Who Died, Experienced SAEs, Experienced AEs or Who Discontinued Due to AEs During the ST Study
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Number of Participants Who Experienced Drug-related SAEs and Drug-related AEs During the ST Study
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Number of Participants With AEs of Special Interest During the ST Study
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
Number of Participants With Marked Abnormalities (MAs) in Hematology During the ST Study: Hemoglobin, Hematocrit, Platelet Count, Erythrocytes and Leukocytes
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Number of Participants With MAs in Hematology During the ST Study: Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
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)
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
Number of Participants With MAs in Serum Chemistry During the ST Study: Creatinine, Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total) and Protein (Total)
Timepoint [12] 0 0
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.
Secondary outcome [13] 0 0
Number of Participants With MAs in Serum Chemistry During the ST Study: Glucose (Fasting Serum), Albumin, Glucose (Serum), Phosphorous (Inorganic) and Uric Acid
Timepoint [13] 0 0
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.
Secondary outcome [14] 0 0
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)
Timepoint [14] 0 0
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.
Secondary outcome [15] 0 0
Number of Participants With Anti-nuclear Antibody (ANA) Category at Day 113 of the ST Study
Timepoint [15] 0 0
Day 113.
Secondary outcome [16] 0 0
Number of Participants With Anti-double Stranded DNA (dsDNA) Category at Day 113 of the ST Study
Timepoint [16] 0 0
Day 113.
Secondary outcome [17] 0 0
Number of Participants With Clinically Meaningful Vital Signs During the ST Study
Timepoint [17] 0 0
At screening and on days 1,15,29,43, 57, 85 and 113.
Secondary outcome [18] 0 0
Minimum Plasma Concentration (Cmin) at Each Visit During the 4 Month Treatment Period of the ST Study
Timepoint [18] 0 0
Days 1, 15, 29, 43, 57, 85 and 113.
Secondary outcome [19] 0 0
Number of Participants With Abatacept Induced Antibody Responses Over Time During the LTE Study (ECL Method) - All Treated Participants in LTE Study
Timepoint [19] 0 0
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
Secondary outcome [20] 0 0
Change From Baseline in DAS28-CRP Score in the LTE Study - All Treated Participants in LTE Study
Timepoint [20] 0 0
Baseline, Day 113, Day 1345
Secondary outcome [21] 0 0
Number of Participants With Clinically Meaningful Improvement From Baseline in the LTE Study - All Treated Participants in LTE Study
Timepoint [21] 0 0
Baseline, Day 113, Day 1345
Secondary outcome [22] 0 0
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
Timepoint [22] 0 0
Day 113, Day 1345
Secondary outcome [23] 0 0
Change From Baseline in HAQ-DI in the LTE Study - All Treated Participants in LTE Study
Timepoint [23] 0 0
Baseline, Day 113, Day 1345
Secondary outcome [24] 0 0
Number of Participants With HAQ Responses in the LTE Study - All Treated Participants in the LTE STudy
Timepoint [24] 0 0
Baseline, Day 113, Day 1345
Secondary outcome [25] 0 0
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
Timepoint [25] 0 0
Continuously from start of LTE period up to 7 days post the last dose
Secondary outcome [26] 0 0
Change From Baseline in DAS28-CRP Score and Physical Function (HAQ-DI) Score in the LTE Study - Abatacept Monotherapy Subgroup
Timepoint [26] 0 0
Baseline, Day 113, Day 1345
Secondary outcome [27] 0 0
Number of Participants in DAS 28-CRP Remission and Low Disease Activity (LDA) in the LTE Study - Abatacept Monotherapy Subgroup
Timepoint [27] 0 0
Day 113, Day 1345
Secondary outcome [28] 0 0
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
Timepoint [28] 0 0
Continuously from start of LTE Study up to 56 days post the last dose
Secondary outcome [29] 0 0
Number of Participants With AEs of Special Interest During the LTE Study - All Treated Participants in LTE Study
Timepoint [29] 0 0
Continuously from start of LTE Study up to 56 days post the last dose
Secondary outcome [30] 0 0
Number of Participants With Marked Abnormalities (MAs) in Hematology During the LTE Period - All Treated Participants in LTE Study
Timepoint [30] 0 0
Continuously from start of LTE Study up to 56 days post the last dose
Secondary outcome [31] 0 0
Number of Participants With MAs in Serum Chemistry (Liver and Kidney Function) During the LTE Period - All Treated Participants in LTE Study
Timepoint [31] 0 0
Continuously from start of LTE Study up to 56 days post the last dose
Secondary outcome [32] 0 0
Number of Participants With MAs in Serum Chemistry (Electrolytes, Glucose, Protein, and Metabolite) During the LTE Period - All Treated Participants in LTE Study
Timepoint [32] 0 0
Continuously from start of LTE Study up to 56 days post the last dose
Secondary outcome [33] 0 0
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
Timepoint [33] 0 0
Continuously from start of LTE Study up to 56 days post the last dose

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2014
Sample size
Target
Accrual to date
Final
119
Recruitment in Australia
Recruitment state(s)
QLD,TAS,VIC
Recruitment hospital [1] 0 0
Local Institution - Maroochydore
Recruitment hospital [2] 0 0
Local Institution - Hobart
Recruitment hospital [3] 0 0
Local Institution - Malvern
Recruitment postcode(s) [1] 0 0
4558 - Maroochydore
Recruitment postcode(s) [2] 0 0
7001 - Hobart
Recruitment postcode(s) [3] 0 0
3144 - Malvern
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Mexico
State/province [13] 0 0
Distrito Federal
Country [14] 0 0
Mexico
State/province [14] 0 0
Jalisco
Country [15] 0 0
South Africa
State/province [15] 0 0
Kwa Zulu Natal
Country [16] 0 0
South Africa
State/province [16] 0 0
Western Cape

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT00547521
Trial related presentations / publications
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00547521