Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis

Verified by: Bristol-Myers Squibb, December 2010
First Received: November 1, 2004 | Last Updated: December 21, 2010 | Phase: Phase 3 | Start Date: February 2005
Overall Status: Completed | Estimated Enrollment: 431
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The purpose of this clinical research study is to learn if Abatacept or Infliximab in combination with Methotrexate demonstrate a greater reduction in disease activity over placebo...

Brief Summary

Official Title: “A Phase IIIB, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Comparative Study of Abatacept or Infliximab in Combination With Methotrexate in Controlling Disease Activity in Subjects With Rheumatoid Arthritis Having an Inadequate Clinical Response to Methotrexate”

The purpose of this clinical research study is to learn if Abatacept or Infliximab in combination with Methotrexate demonstrate a greater reduction in disease activity over placebo.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
  • Study Primary Completion Date: July 2009

Intervention(s) in this Clinical Trial

  • Drug: Abatacept (ABA) + Methotrexate (MTX), double-blind (DB)
    • Abatacept, intravenous (IV) Solution, Infusion, Depends on participant weight, Monthly, 12 months.
  • Drug: Infliximab (INF) + MTX, DB
    • Infliximab, IV Solution, Infusion, Depends on participant weight, Every 2 Months, 12 months.
  • Drug: Placebo (PLA) + MTX, DB
    • Placebo, IV Solution, Infusion, Depends on participant weight, Monthly, 6 months.
  • Drug: PLA + MTX switched to ABA+ MTX, DB
    • Placebo=IV Solution, Infusion, Depends on participant weight, Monthly, 6 months. Abatacept=IV Solution, Infusion, Depends on participant weight, Monthly, 6 months
  • Drug: ABA, open-label (OL)
    • Abatacept, IV solution, Infusion. Depends on participant weight, Monthly, 12+ months

Arms, Groups and Cohorts in this Clinical Trial

  • Active Comparator: Abatacept (ABA) + Methotrexate (MTX) (double-blind [DB])
    • Days 1-365
  • Active Comparator: Infliximab + MTX (DB)
    • Days 1-365
  • Placebo Comparator: Placebo + MTX (DB)
    • Days 1-197
  • Experimental: Placebo + MTX switched to abatacept + MTX (DB)
    • Participants received placebo plus methotrexate for days 1-197, and abatacept plus methotrexate for days 198-365
  • Experimental: Abatacept (open-label)
    • Days 365 to 729 All participants receive Active Drug

Outcome Measures for this Clinical Trial

Primary Measures

  • DB; Adjusted Mean Change From Baseline to Day 197 in Disease Activity Score (DAS) 28 Score (Erythrocyte Sedimentation Rate [ESR]) For ABA Versus PLA (Last Observation Carried Forward [LOCF] Analysis)
    • Time Frame: Baseline (Day 1), 6 months (Day 197)
      Safety Issue?: No
  • OL; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, and AEs Leading to Discontinuation
    • Time Frame: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
      Safety Issue?: Yes
  • OL; Number of Participants With AEs of Special Interest
    • Time Frame: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
      Safety Issue?: Yes
  • OL; Number of Participants With Select Hematologic Laboratory Abnormalities
    • Time Frame: From Day 366 through end of OL (range from 1.9 months to 42.3 months)
      Safety Issue?: Yes
  • OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
    • Time Frame: From Day 366 through end of OL (range from 1.9 months to 42.3 months)
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
    • Time Frame: Baseline (Day 1), Day 365
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 365 in Platelets
    • Time Frame: Baseline (Day 1), Day 365
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 365 in Hematocrit
    • Time Frame: Baseline (Day 1), Day 365
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 365 in White Blood Cells
    • Time Frame: Baseline (Day 1), Day 365
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 365 in Erythrocytes
    • Time Frame: Baseline (Day 1), Day 365
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 365 in Electrolytes
    • Time Frame: Baseline (Day 1), Day 365
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
    • Time Frame: Baseline (Day 1), Day 365
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
    • Time Frame: Baseline (Day 1), Day 365
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
    • Time Frame: Baseline (Day 1), Day 729
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 729 in Platelets
    • Time Frame: Baseline (Day 1), Day 729
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 729 in Hematocrit
    • Time Frame: Baseline (Day 1), Day 729
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 729 in White Blood Cells
    • Time Frame: Baseline (Day 1), Day 729
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 729 in Erythrocytes
    • Time Frame: Baseline (Day 1), Day 729
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 729 in Electrolytes
    • Time Frame: Baseline (Day 1), Day 729
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
    • Time Frame: Baseline (Day 1), Day 729
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
    • Time Frame: Baseline (Day 1), Day 729
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
    • Time Frame: Baseline (Day 1), Day 1121
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1121 in Platelets
    • Time Frame: Baseline (Day 1), Day 1121
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1121 in Hematocrit
    • Time Frame: Baseline (Day 1), Day 1121
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1121 in White Blood Cells
    • Time Frame: Baseline (Day 1), Day 1121
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1121 in Erythrocytes
    • Time Frame: Baseline (Day 1), Day 1121
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1121 in Electrolytes
    • Time Frame: Baseline (Day 1), Day 1121
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
    • Time Frame: Baseline (Day 1), Day 1121
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
    • Time Frame: Baseline (Day 1), Day 1121
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
    • Time Frame: Baseline (Day 1), Day 1513
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1513 in Platelets
    • Time Frame: Baseline (Day 1), Day 1513
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1513 in Hematocrit
    • Time Frame: Baseline (Day 1), Day 1513
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1513 in White Blood Cells
    • Time Frame: Baseline (Day 1), Day 1513
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1513 in Erythrocytes
    • Time Frame: Baseline (Day 1), Day 1513
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1513 in Electrolytes
    • Time Frame: Baseline (Day 1), Day 1513
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
    • Time Frame: Baseline (Day 1), Day 1513
      Safety Issue?: Yes
  • OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
    • Time Frame: Baseline (Day 1), Day 1513
      Safety Issue?: Yes
  • OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
    • Time Frame: Days 365, 729, 1121, and 1513
      Safety Issue?: Yes
  • OL; Mean Heart Rate (HR) During Open Label Period
    • Time Frame: Days 365, 729, 1121, and 1513
      Safety Issue?: Yes
  • OL; Mean Temperature (T) During Open Label Period
    • Time Frame: Days 365, 729, 1121, and 1513
      Safety Issue?: Yes

Secondary Measures

  • DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis)
    • Time Frame: Baseline (Day 1), 6 months (Day 197)
      Safety Issue?: No
  • DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF
    • Time Frame: From Day 1 through Day 365 (12 months)
      Safety Issue?: No
  • DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197
    • Time Frame: DB Day 197
      Safety Issue?: No
  • DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365
    • Time Frame: DB Day 365
      Safety Issue?: No
  • DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
    • Time Frame: Baseline (Day 1), 6 months (Day 197)
      Safety Issue?: No
  • DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
    • Time Frame: Baseline (Day 1), 12 months (Day 365)
      Safety Issue?: No
  • DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
    • Time Frame: Baseline (Day 1), 6 months (Day 197)
      Safety Issue?: No
  • DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
    • Time Frame: Baseline (Day 1), 12 months (Day 365)
      Safety Issue?: No
  • DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
    • Time Frame: DB Day 365
      Safety Issue?: No
  • DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
    • Time Frame: DB Day 197
      Safety Issue?: No
  • DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
    • Time Frame: DB Day 365
      Safety Issue?: No
  • DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 197
    • Time Frame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
    • Time Frame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 1 Through Day 365
    • Time Frame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, and AEs Leading to Discontinuation From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
    • Time Frame: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
    • Time Frame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
    • Time Frame: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365
    • Time Frame: From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365
    • Time Frame: From Baseline (Day 1) through Day 197, or Day 1 through Day 365, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365
    • Time Frame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
    • Time Frame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
    • Time Frame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
      Safety Issue?: Yes
  • DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)
    • Time Frame: Day 1 through day 365
      Safety Issue?: No
  • DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
    • Time Frame: Day 1 through day 365
      Safety Issue?: No
  • OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
    • Time Frame: Baseline (Day 1), Day 365, Day 533, Day 729
      Safety Issue?: No
  • OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
    • Time Frame: Baseline (Day 1), Day 365, Day 533, Day 729
      Safety Issue?: No
  • OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
    • Time Frame: DB Days 365, 533, and 729
      Safety Issue?: No
  • OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
    • Time Frame: DB Day 197, Day 365, Day 533, Day 729
      Safety Issue?: No
  • OL; Percentage of Participants Who Achieved Major Clinical Response
    • Time Frame: Defined from the date of achieving ACR 70 response to 6 months post response
      Safety Issue?: No
  • OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
    • Time Frame: OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729
      Safety Issue?: No
  • OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
    • Time Frame: Day 1 (Baseline), Day 729
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion Criteria:

  • Diagnosis of Rheumatoid Arthritis
  • At least 3 months prior treatment with Methotrexate (MTX)
  • At least 10 swollen joints and 12 tender joints and C-Reactive Protein of at least 1 mg/dl
  • Washout required for other disease modifying anti-rheumatic drugs (DMARDS)

Exclusion Criteria:

  • participants who have failed more than 3 DMARDs
  • participants previously treated with an approved biologic drug
  • History of cancer in the last 5 years
  • Severe or recurrent bacterial infection
  • Any previous or current medical conditions that are contraindications to the use of TNF blocking agents
  • Women of Child Bearing Potential

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Clinical Trial Investigator Information

Lead Investigator: Bristol-Myers Squibb Industry

Overall Clinical Trial Officials and Contacts

Bristol-Myers Squibb Study Director Bristol-Myers Squibb  

Additional Information

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00095147

Study ID Number: IM101-043

ClinicalTrials.gov Identifier: NCT00095147

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

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