Phase IIIB Subcutaneous Abatacept Monotherapy Study

NCT00547521 | Completed Phase 3 Results

• 1 other identifier: IM101-173
• Study Type: interventional
• Target: 119
• Locations: 4 countries
• Sites: 22

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

Conditions

Rheumatoid Arthritis (RA)

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (Enzyme-linked Immunosorbent Assay [ELISA] Method) at Day 113 of the ST Study

  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.

  Day 113

• Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses (ELISA Method) Over Time During the ST Study

  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.

  Day 15, 29, 43, 57, 85,113 and 28, 56, and 85 days post last dose.

• Number of Participants With Positive Anti-abatacept Responses to Abatacept (Meso-Scale Discovery [MSD] Electrochemiluminescence [ECL] Assay Method) Over Time During the ST Study

  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.

  Day 15, 29, 43, 57, 85,113 and 28, 56 and 85 days post last dose.

• Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for ELISA Results)

  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.

  Day 113.

• Immunogenicity in MTX Naive and MTX-previous Users in Cohort 1 at Day 113 of the ST Study (for MSD Results)

  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.

  Day 113.

• 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)

  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.

  Baseline and on day 15, 29, 43, 57, 85 and 113

• 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)

  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.

  Baseline and day 15, 29, 43, 57, 85 and 113.

Secondary Outcomes (33)

• Change From Baseline in DAS28-CRP Score at End of 4-month (Day 113) of the ST Study

  Baseline and Month 4 (Day113).

• 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).

• 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).

• 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.

Study Arms (2)

Subcutaneous (SC) Abatacept + Methotrexate (MTX) Cohort

EXPERIMENTAL

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.

Drug: abatacept; Drug: Methotrexate (MTX)

SC Abatacept Monotherapy Cohort

EXPERIMENTAL

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.

Drug: abatacept

Interventions

abatacept DRUG

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

Also known as: BMS-188667, Orencia®

SC Abatacept Monotherapy Cohort; Subcutaneous (SC) Abatacept + Methotrexate (MTX) Cohort

Methotrexate (MTX) DRUG

Participants who were currently receiving methotrexate at a stable dose ≥ 10 mg for at least 4 weeks

Subcutaneous (SC) Abatacept + Methotrexate (MTX) Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (22)

Rheumatology Associates Of North Alabama

Huntsville, Alabama, 35801, United States

Location

Coastal Clinical Research Inc

Mobile, Alabama, 36608, United States

Location

Stanford University School Of Medicine

Palo Alto, California, 94304, United States

Location

Boulder Medical Center

Boulder, Colorado, 80304, United States

Location

The Arthritis Center

Palm Harbor, Florida, 34684, United States

Location

Medical Towers South

Louisville, Kentucky, 40298, United States

Location

Westroads Medical Group

Omaha, Nebraska, 68114, United States

Location

Regional Rheumatology Associates

Binghamton, New York, 13905, United States

Location

Physicians East, Pa

Greenville, North Carolina, 27834, United States

Location

Healthcare Research Consultants

Tulsa, Oklahoma, 74135, United States

Location

East Penn Rheumatology Associates

Bethlehem, Pennsylvania, 18015, United States

Location

Altoona Center For Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Low Country Rheumatology, Pa

Charleston, South Carolina, 29406, United States

Location

Columbia Arthritis Center

Columbia, South Carolina, 29204, United States

Location

Rheumatic Disease Center

Glendale, Wisconsin, 53217, United States

Location

Local Institution

Maroochydore, Queensland, 4558, Australia

Location

Local Institution

Hobart, Tasmania, 7001, Australia

Location

Local Institution

Malvern, Victoria, 3144, Australia

Location

Local Institution

Guadalajara, Jalisco, 44100, Mexico

Location

Local Institution

D.f., Mexico City, 06700, Mexico

Location

Local Institution

Berea, KwaZulu-Natal, 4001, South Africa

Location

Local Institution

Panorama, Western Cape, 7500, South Africa

Location

Related Publications (1)

• 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.

  PMID: 23097311 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Abatacept; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2007
• First Posted: October 22, 2007
• Study Start: December 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: February 1, 2014
• Last Updated: March 23, 2015
• Results First Posted: January 24, 2011

Record last verified: 2015-03

Locations

AU (3); ME (2); US (15); ZA (2)