Remission and Joint Damage Progression in Early Rheumatoid Arthritis

Official Title: “A Phase IIIB Multi-center, Randomized, Double-Blind Study to Evaluate Remission and Joint Damage Progression in Methotrexate Naive Early Erosive RA Subjects Treated With Abatacept Plus Methotrexate Compared With Methotrexate”

This is a world wide study to evaluate the remission and joint damage in subjects treated with abatacept in addition to methotrexate versus subjects who receive methotrexate along with a placebo.

Intervention(s) in this Clinical Trial

• Drug: Abatacept
  • abatacept 10 mg/kg IV monthly, methotrexate weekly, for 24 months
• Drug: placebo
  • placebo IV, monthly, methotrexate weekly for 12 months followed by abatacept 10 mg/kg IV monthly, methotrexate weekly for 12 months
• Drug: methotrexate
  • Oral, titrated to at least 15 mg per week not to exceed 20 mg per week administered every 28 days from Month 12 to Month 24

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: ABA + MTX
  • abatacept 10 mg/kg intravenous (IV) + methotrexate
• Active Comparator: Placebo (PLA) + MTX
  • placebo IV + methotrexate

Primary Measures

• Number of Participants in DAS 28 C-reactive Protein (CRP) Remission at Month 12
  • Time Frame: Month 12
    Safety Issue?: No
• Mean Change From Baseline in Radiographic Total Score to Month 12
  • Time Frame: Baseline, Month 12
    Safety Issue?: No
• Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Due to AEs During the Open-Label Period
  • Time Frame: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
    Safety Issue?: Yes
• Number of Participants With Serious Adverse Events Reported During the Open-Label Period
  • Time Frame: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
    Safety Issue?: Yes
• Number of Participants With SAEs With an Outcome of Death During the Open-label Period
  • Time Frame: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
    Safety Issue?: Yes
• Incidence Rates of Autoimmune Disorders in ABA-Treated Participants
  • Time Frame: Double Blind Period (+56 days post last dose in double-blind period or start of open-label period, whichever came first). Open-label period (56 days post last dose in the open-label period or start of maintenance sub-study, whichever came first).
    Safety Issue?: Yes
• Incidence Rates of Infections and Infestations of Adverse Events in ABA-Treated Participants
  • Time Frame: Double Blind Period (+56 days post last dose in double-blind period or start of the open-label period, whichever came first). Open-label period (56 days post last dose in open-label period or start of maintenance sub-study, whichever came first).
    Safety Issue?: Yes
• Incidence Rates of Malignant Neoplasm Adverse Events in ABA-Treated Participants
  • Time Frame: Double Blind Period (+56 days post last dose in double-blind period or start of the open-label period, whichever came first). Open-label period (56 days post last dose in open-label period or start of maintenance sub-study, whichever came first).
    Safety Issue?: Yes
• Number of Participants With a Serious Acute-Infusional AE of Anaphylactic Shock During Open-Label Period
  • Time Frame: Open-Label Period (Month 12 to Month 24)
    Safety Issue?: Yes
• Number of Participants With Select Blood Chemistry Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
  • Time Frame: Continuously through open-label period (from Month 12 to Month 24). Includes data up to 56 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
    Safety Issue?: Yes
• Number of Participants With Hematology Laboratory Values Meeting the Marked Abnormality Criteria During the Open-Label Period
  • Time Frame: Continuously from start of open-label period up to 56 days post the last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
    Safety Issue?: Yes

Secondary Measures

• Number of Participants With American College of Rheumatology (ACR) 50 Response at Month 12
  • Time Frame: Month 12
    Safety Issue?: No
• Number of Participants With Major Clinical Response (MCR) at Month 12
  • Time Frame: Month 12
    Safety Issue?: No
• Adjusted Mean Change From Baseline in DAS-28-CRP Score to Month 12
  • Time Frame: Baseline, Month 12
    Safety Issue?: No
• Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 12
  • Time Frame: Month 12
    Safety Issue?: No
• Adjusted Mean Change in Short Form 36 (SF-36) From Baseline to Month 12
  • Time Frame: Baseline, Month 12
    Safety Issue?: No
• Mean Change From Baseline in Radiographic Erosion and Joint Space Narrowing (JSN) Scores to Month 12
  • Time Frame: Baseline, Month 12
    Safety Issue?: No
• Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses in the Double-blind Period as Analyzed by Enzyme-linked-immunosorbent Serologic Assay (ELISA)
  • Time Frame: includes data up to approximately 85 days past the last dose of the double-blind period or start of the open-label period, whichever occurred first.
    Safety Issue?: No
• Number of Participants With Anti-abatacept or Anti-CTLA4-T Responses During the Open-Label Period (From Month 12 to Month 24) as Analyzed by ELISA
  • Time Frame: Includes open-label data up to approximately 85 days post last dose in the open-label period or start of the maintenance sub-study, whichever occurred first.
    Safety Issue?: No
• Number of Participants With Health Assessment Questionnaire (HAQ) Response at Month 24
  • Time Frame: Baseline, Month 24
    Safety Issue?: No
• Mean Change From Baseline in Radiographic Total, Erosion and JSN Scores to Month 24
  • Time Frame: Baseline, Month 24
    Safety Issue?: No
• Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) From Baseline at Month 24
  • Time Frame: Baseline, Month 24
    Safety Issue?: No
• Number of Participants Without Radiographic Progression (as Measured by in Erosion Scores, JSN Scores, and Total Scores) at Month 24 in Participants Without Progression at Month 12
  • Time Frame: Month 12, Month 24
    Safety Issue?: No
• Mean Difference Observed in Change From Baseline to Month 12 and Between Month 12 and Month 24 in Radiographic Scores (Total Score)
  • Time Frame: Baseline, Month 12, Month 24
    Safety Issue?: No
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuations Reported During the Double-blind Period
  • Time Frame: Includes data up to 56 days post the last dose in the double-blind period or start of the open-label period, whichever occurred first.
    Safety Issue?: Yes
• Number of Participants With Laboratory Values Meeting the Marked Abnormality Criteria During the Double-blind Period
  • Time Frame: Includes data up to 56 days post the last dose in the double-blind period or start of the open-label period, whichever occurred first.
    Safety Issue?: Yes

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis (RA) <=2 years; MTX naive or <=10 mg/wk for <=3 weeks. No dose within 3 months prior to informed consent.
• C-Reactive Protein (CRP) >= 4.5 mg/L (after amendment)
• Rheumatoid factor or anti-cyclic citrullinated peptide antibody (anti-CCP) positive
• Tender joints >=12 and swollen joints >=10

Exclusion Criteria:

• Women and men who are not willing to use birth control
• Diagnosed with other rheumatic disease
• History of cancer within 5 years
• Active tuberculosis
• Treatment with another investigation drug within 28 days
• Active bacterial or viral infection

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Bristol-Myers Squibb Industry

Overall Clinical Trial Officials and Contacts

Bristol-Myers Squibb Study Director Bristol-Myers Squibb  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00122382

Study ID Number: IM101-023

ClinicalTrials.gov Identifier: NCT00122382

Health Authority: United States: Food and Drug Administration

BMS Clinical Trials Disclosure

For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm