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

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00095147
First received: November 1, 2004
Last updated: December 21, 2010
Last verified: December 2010
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Abatacept (ABA) + Methotrexate (MTX), double-blind (DB)
Drug: Infliximab (INF) + MTX, DB
Drug: Placebo (PLA) + MTX, DB
Drug: PLA + MTX switched to ABA+ MTX, DB
Drug: ABA, open-label (OL)
Phase 3

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
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome 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) ] [ Designated as safety issue: No ]
    The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or C-reactive protein (CRP), and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.

  • 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) ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

  • 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) ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).

  • 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) ] [ Designated as safety issue: Yes ]
    High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; monocytes: >2000 mm3; eosinophils: >0.750 x 10^3 c/uL;

  • 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) ] [ Designated as safety issue: Yes ]
    Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL

  • OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin [ Time Frame: Baseline (Day 1), Day 365 ] [ Designated as safety issue: Yes ]
    Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN

  • OL; Mean Change From Baseline to Day 365 in Platelets [ Time Frame: Baseline (Day 1), Day 365 ] [ Designated as safety issue: Yes ]
    Platelets (PLT): <0.67 x LLN, >1.5 x ULN

  • OL; Mean Change From Baseline to Day 365 in Hematocrit [ Time Frame: Baseline (Day 1), Day 365 ] [ Designated as safety issue: Yes ]
    Hematocrit: <0.75 x BL

  • OL; Mean Change From Baseline to Day 365 in White Blood Cells [ Time Frame: Baseline (Day 1), Day 365 ] [ Designated as safety issue: Yes ]
    Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.

  • OL; Mean Change From Baseline to Day 365 in Erythrocytes [ Time Frame: Baseline (Day 1), Day 365 ] [ Designated as safety issue: Yes ]
    Erythrocytes: <0.75 x BL

  • OL; Mean Change From Baseline to Day 365 in Electrolytes [ Time Frame: Baseline (Day 1), Day 365 ] [ Designated as safety issue: Yes ]
    Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN

  • 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 ] [ Designated as safety issue: Yes ]
    Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;

  • 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 ] [ Designated as safety issue: Yes ]
    alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN

  • OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin [ Time Frame: Baseline (Day 1), Day 729 ] [ Designated as safety issue: Yes ]
    Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN

  • OL; Mean Change From Baseline to Day 729 in Platelets [ Time Frame: Baseline (Day 1), Day 729 ] [ Designated as safety issue: Yes ]
    Platelets (PLT): <0.67 x LLN, >1.5 x ULN

  • OL; Mean Change From Baseline to Day 729 in Hematocrit [ Time Frame: Baseline (Day 1), Day 729 ] [ Designated as safety issue: Yes ]
    Hematocrit: <0.75 x BL

  • OL; Mean Change From Baseline to Day 729 in White Blood Cells [ Time Frame: Baseline (Day 1), Day 729 ] [ Designated as safety issue: Yes ]
    Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.

  • OL; Mean Change From Baseline to Day 729 in Erythrocytes [ Time Frame: Baseline (Day 1), Day 729 ] [ Designated as safety issue: Yes ]
    Erythrocytes: <0.75 x BL

  • OL; Mean Change From Baseline to Day 729 in Electrolytes [ Time Frame: Baseline (Day 1), Day 729 ] [ Designated as safety issue: Yes ]
    Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN

  • 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 ] [ Designated as safety issue: Yes ]
    Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;

  • 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 ] [ Designated as safety issue: Yes ]
    alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN

  • OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin [ Time Frame: Baseline (Day 1), Day 1121 ] [ Designated as safety issue: Yes ]
    Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN

  • OL; Mean Change From Baseline to Day 1121 in Platelets [ Time Frame: Baseline (Day 1), Day 1121 ] [ Designated as safety issue: Yes ]
    Platelets (PLT): <0.67 x LLN, >1.5 x ULN

  • OL; Mean Change From Baseline to Day 1121 in Hematocrit [ Time Frame: Baseline (Day 1), Day 1121 ] [ Designated as safety issue: Yes ]
    Hematocrit: <0.75 x BL

  • OL; Mean Change From Baseline to Day 1121 in White Blood Cells [ Time Frame: Baseline (Day 1), Day 1121 ] [ Designated as safety issue: Yes ]
    Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.

  • OL; Mean Change From Baseline to Day 1121 in Erythrocytes [ Time Frame: Baseline (Day 1), Day 1121 ] [ Designated as safety issue: Yes ]
    Erythrocytes: <0.75 x BL

  • OL; Mean Change From Baseline to Day 1121 in Electrolytes [ Time Frame: Baseline (Day 1), Day 1121 ] [ Designated as safety issue: Yes ]
    Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN

  • 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 ] [ Designated as safety issue: Yes ]
    Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;

  • 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 ] [ Designated as safety issue: Yes ]
    alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN

  • OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin [ Time Frame: Baseline (Day 1), Day 1513 ] [ Designated as safety issue: Yes ]
    Hemoglobin (HGB): >3 g/dL decrease from BL; total protein: < 0.9 x LLN, >1.1 x ULN; albumin:<0.9 x LLN

  • OL; Mean Change From Baseline to Day 1513 in Platelets [ Time Frame: Baseline (Day 1), Day 1513 ] [ Designated as safety issue: Yes ]
    Platelets (PLT): <0.67 x LLN, >1.5 x ULN

  • OL; Mean Change From Baseline to Day 1513 in Hematocrit [ Time Frame: Baseline (Day 1), Day 1513 ] [ Designated as safety issue: Yes ]
    Hematocrit: <0.75 x BL

  • OL; Mean Change From Baseline to Day 1513 in White Blood Cells [ Time Frame: Baseline (Day 1), Day 1513 ] [ Designated as safety issue: Yes ]
    Leukocytes: <0.75 x LLN, >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; basophils: > 400 mm3; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL, >7.50 x 10^3 c/uL.

  • OL; Mean Change From Baseline to Day 1513 in Erythrocytes [ Time Frame: Baseline (Day 1), Day 1513 ] [ Designated as safety issue: Yes ]
    Erythrocytes: <0.75 x BL

  • OL; Mean Change From Baseline to Day 1513 in Electrolytes [ Time Frame: Baseline (Day 1), Day 1513 ] [ Designated as safety issue: Yes ]
    Sodium (Na): <0.95 x LLN, >1.05 x ULN; potassium (K): <0.9 x LLN, >1.1 x ULN; chloride (Cl): <0.9 x LLN, >1.1 x ULN

  • 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 ] [ Designated as safety issue: Yes ]
    Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; calcium (Ca): <0.8 x LLN, >1.2 x ULN; phosphorous (P): <0.75 x LLN, >1.2 5 x ULN; serum glucose (Glu): <65 mg/dL, >220 mg/dL; fasting serum Glu: <0.8 x LLN, >1.5 x ULN; uric acid: >1.5 x ULN;

  • 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 ] [ Designated as safety issue: Yes ]
    alanine aminotransferase (ALT): >3 x ULN; aspartate aminotransferase (AST): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Alkaline phosphatase (ALP): >2 x ULN

  • OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period [ Time Frame: Days 365, 729, 1121, and 1513 ] [ Designated as safety issue: Yes ]
    Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP), units=mm mercury (Hg)

  • OL; Mean Heart Rate (HR) During Open Label Period [ Time Frame: Days 365, 729, 1121, and 1513 ] [ Designated as safety issue: Yes ]
    Heart Rate (HR), units=beats per minute (bpm)

  • OL; Mean Temperature (T) During Open Label Period [ Time Frame: Days 365, 729, 1121, and 1513 ] [ Designated as safety issue: Yes ]
    Temperature (T), units=degrees Celcius


Secondary Outcome 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) ] [ Designated as safety issue: No ]
    The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.

  • 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) ] [ Designated as safety issue: No ]
    The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). Clinically significant response= decrease in DAS28 score of >1.2 from baseline. DAS28 AUC can be calculated from the DAS28 score versus time curve, which provides an assessment of changes in disease activity over time.

  • DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197 [ Time Frame: DB Day 197 ] [ Designated as safety issue: No ]
    The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.

  • DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365 [ Time Frame: DB Day 365 ] [ Designated as safety issue: No ]
    The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.

  • DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis) [ Time Frame: Baseline (Day 1), 6 months (Day 197) ] [ Designated as safety issue: No ]
    The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.

  • DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis) [ Time Frame: Baseline (Day 1), 12 months (Day 365) ] [ Designated as safety issue: No ]
    The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.

  • 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) ] [ Designated as safety issue: No ]
    The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.

  • 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) ] [ Designated as safety issue: No ]
    The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.

  • 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 ] [ Designated as safety issue: No ]
    The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute: <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute: 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute: >5.1 or <0.6 change from BL)

  • DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197 [ Time Frame: DB Day 197 ] [ Designated as safety issue: No ]
    The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.

  • DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365 [ Time Frame: DB Day 365 ] [ Designated as safety issue: No ]
    The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.

  • 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 ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

  • 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 ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).

  • 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 ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

  • 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 ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

  • 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 ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).

  • 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 ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs, including all infections, serious infections, autoimmune disorders; malignancies; and acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion).

  • 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 ] [ Designated as safety issue: Yes ]
    Seated Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.

  • 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 ] [ Designated as safety issue: Yes ]
    Heart Rate (HR) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.

  • 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 ] [ Designated as safety issue: Yes ]
    Temperature (T) was assessed as clinically significant or relevant at the discretion of the Clinical Investigator. Criteria may have varied between institutions.

  • 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 ] [ Designated as safety issue: Yes ]
    High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL

  • 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 ] [ Designated as safety issue: Yes ]
    High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; creatinine: >4 x BL

  • DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay) [ Time Frame: Day 1 through day 365 ] [ Designated as safety issue: No ]
    ECL screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. Cytotoxic leukocyte antigen 4 (CTLA4) and Possibly Immunoglobulin (Ig) Category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction Category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.

  • 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 ] [ Designated as safety issue: No ]
    Infliximab levels were measured using a microplate enzyme-linked immunosorbant assay (ELISA) with infliximab bound to immobilized recombinant tumor necrosis factor (TNF)-alpha. Bound infliximab is detected utilizing a horseradish peroxidase-conjugated anti-human IgG Fc(fragment, crystallizable region)-specific). The enzyme turns over the substrate O-phenlenediamine to a chromogenic product that is measured at 490 nm. The cut-off value was 1.40 ug/mL; this was based on the mean (+ 3 SD) value in serum samples from 40 participants who had never received infliximab.

  • OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score [ Time Frame: Baseline (Day 1), Day 365, Day 533, Day 729 ] [ Designated as safety issue: No ]
    The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.

  • 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 ] [ Designated as safety issue: No ]
    The DAS28 is a continuous disease measure which is a composite of 4 variables: the 28 tender joint count, the 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. The DAS28 has numeric thresholds that define high disease activity (> 5.1), low disease activity (< 3.2) and remission (< 2.6). A clinically significant response is a decrease in DAS28 score of >1.2 from baseline.

  • 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 ] [ Designated as safety issue: No ]
    The DAS28 is a continuous disease measure composite of 4 variables: 28 tender joint count, 28 swollen joint count, ESR or CRP, and participant assessment of disease activity measure on a visual analogue scale. High disease activity= > 5.1, low disease activity= < 3.2, and remission= < 2.6. Clinically significant response= decrease of >1.2 from baseline. Utilizing EULAR response criteria, DAS28 categorical responses define a good (absolute <3.2 or >1.2 improvement from baseline [BL]), moderate (absolute 3.2-5.1 or 0.6-1.2 change from BL), or no response (absolute >5.1 or <0.6 change from BL)

  • OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time [ Time Frame: DB Day 197, Day 365, Day 533, Day 729 ] [ Designated as safety issue: No ]
    The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joint counts, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein [CRP]). The evaluation for 50% improvement (ACR 50) and 70% improvement (ACR 70) follow similarly.

  • 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 ] [ Designated as safety issue: No ]
    Major Clinical Response was defined as a continuous ACR 70 for six months.

  • 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 ] [ Designated as safety issue: No ]
    The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.

  • OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI [ Time Frame: Day 1 (Baseline), Day 729 ] [ Designated as safety issue: No ]
    The disability section of the full HAQ includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3= unable to do. Higher scores= greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ response=an improvement of at least 0.3 units from baseline in HAQ disability Index.


Enrollment: 431
Study Start Date: February 2005
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Abatacept (ABA) + Methotrexate (MTX) (double-blind [DB])
Days 1-365
Drug: Abatacept (ABA) + Methotrexate (MTX), double-blind (DB)
Abatacept, intravenous (IV) Solution, Infusion, Depends on participant weight, Monthly, 12 months.
Other Name: Orencia
Active Comparator: Infliximab + MTX (DB)
Days 1-365
Drug: Infliximab (INF) + MTX, DB
Infliximab, IV Solution, Infusion, Depends on participant weight, Every 2 Months, 12 months.
Placebo Comparator: Placebo + MTX (DB)
Days 1-197
Drug: Placebo (PLA) + MTX, DB
Placebo, IV Solution, Infusion, Depends on participant weight, Monthly, 6 months.
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
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
Other Name: Orencia
Experimental: Abatacept (open-label)
Days 365 to 729 All participants receive Active Drug
Drug: ABA, open-label (OL)
Abatacept, IV solution, Infusion. Depends on participant weight, Monthly, 12+ months
Other Name: Orencia

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00095147

  Hide Study Locations
Locations
United States, Alabama
Local Institution
Huntsville, Alabama, United States
United States, Colorado
Local Institution
Denver, Colorado, United States
United States, Florida
Local Institution
Boca Raton, Florida, United States
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Ft Lauderdale, Florida, United States
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Largo, Florida, United States
United States, Indiana
Local Institution
Indianapolis, Indiana, United States
United States, Louisiana
Local Institution
New Orleans, Louisiana, United States
United States, Massachusetts
Local Institution
Springfield, Massachusetts, United States
Local Institution
Worcester, Massachusetts, United States
United States, Mississippi
Local Institution
Flowood, Mississippi, United States
United States, New York
Local Institution
Syracuse, New York, United States
United States, North Carolina
Local Institution
Charlotte, North Carolina, United States
United States, Ohio
Local Institution
Cincinnati, Ohio, United States
United States, Oklahoma
Local Institution
Oklahoma City, Oklahoma, United States
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Tulsa, Oklahoma, United States
United States, Pennsylvania
Local Institution
Bethlehem, Pennsylvania, United States
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Willow Grove, Pennsylvania, United States
United States, Texas
Local Institution
Austin, Texas, United States
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Dallas, Texas, United States
Argentina
Local Institution
Capital Federal, Buenos Aires, Argentina
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Quilmes, Buenos Aires, Argentina
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Buenos Aires, Argentina
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Cordoba, Argentina
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Tucuman, Argentina
Australia, Queensland
Local Institution
Cairns, Queensland, Australia
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Cotton Tree, Queensland, Australia
Australia, Victoria
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Clayton, Victoria, Australia
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Heidelberg, Victoria, Australia
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Malvern, Victoria, Australia
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Parkville, Victoria, Australia
Australia, Western Australia
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Perth, Western Australia, Australia
Brazil
Local Institution
Curitiba, Parana, Brazil
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Recife, Pernambuco, Brazil
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Porto Alegre, Rio Grande Do Sul, Brazil
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Rio De Janeiro, Brazil
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Sao Paulo, Brazil
Canada, Alberta
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Calgary, Alberta, Canada
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Edmonton, Alberta, Canada
Canada, Manitoba
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Winnipeg, Manitoba, Canada
Canada, Newfoundland and Labrador
Local Institution
St. Johns, Newfoundland and Labrador, Canada
Canada, Ontario
Local Institution
Hamilton, Ontario, Canada
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Kitchener, Ontario, Canada
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Ottawa, Ontario, Canada
Canada, Quebec
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Montreal, Quebec, Canada
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Ste-Foy, Quebec, Canada
Canada, Saskatchewan
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Saskatoon, Saskatchewan, Canada
Canada
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Kitchener, Canada, ON
Czech Republic
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Prague 2, Czech Republic
Denmark
Local Institution
Copenhagen, Denmark
Korea, Republic of
Local Institution
Seoul, Korea, Republic of
Mexico
Local Institution
Tijuana, Baja California, Mexico
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Mexico, Distrito Federal, Mexico
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Leon, Guanajuato, Mexico
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Guadalajara, Jalisco, Mexico
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Monterrey, Nuevo Leon, Mexico
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San Luis Potosi, Mexico
Peru
Local Institution
Lima, Peru
Poland
Local Institution
Poznan, Poland
Local Institution
Sopot, Poland
Local Institution
Warszawa, Poland
Puerto Rico
Local Institution
Rio Piedras, Puerto Rico
Russian Federation
Local Institution
Moscow, Russian Federation
South Africa
Local Institution
Muckleneuk, Gauteng, South Africa
Local Institution
Berea, Kwa Zulu Natal, South Africa
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Panorama, Western Cape, South Africa
Spain
Local Institution
A Coruna, Spain
Local Institution
Barcelona, Spain
Local Institution
Cordoba, Spain
Local Institution
Madrid, Spain
Sweden
Local Institution
Falun, Sweden
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Linkoping, Sweden
Local Institution
Lund, Sweden
Local Institution
Stockholm, Sweden
Local Institution
Uppsala, Sweden
Switzerland
Local Institution
Bern, Switzerland
Local Institution
St. Gallen, Switzerland
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00095147     History of Changes
Other Study ID Numbers: IM101-043
Study First Received: November 1, 2004
Results First Received: October 26, 2010
Last Updated: December 21, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Abatacept
Methotrexate
Infliximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on September 30, 2014