Clinical trial NCT00095147: Abatacept and Infliximab in Combination With Methotrexate in Subjects With Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2004-11-02
Enrollment: 431
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: Baseline (Day 1), 6 months (Day 197)
measure: 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
timeFrame: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
measure: OL; Number of Participants With AEs of Special Interest
timeFrame: From beginning of OL (Day 366) through end of OL (range from 1.9 months to 42.3 months)
measure: OL; Number of Participants With Select Hematologic Laboratory Abnormalities
timeFrame: From Day 366 through end of OL (range from 1.9 months to 42.3 months)
measure: OL; Number of Participants With Select Blood Chemistry Laboratory Abnormalities
timeFrame: From Day 366 through end of OL (range from 1.9 months to 42.3 months)
measure: OL; Mean Change From Baseline to Day 365 in Hemoglobin, Total Protein, and Albumin
timeFrame: Baseline (Day 1), Day 365
measure: OL; Mean Change From Baseline to Day 365 in Platelets
timeFrame: Baseline (Day 1), Day 365
measure: OL; Mean Change From Baseline to Day 365 in Hematocrit
timeFrame: Baseline (Day 1), Day 365
measure: OL; Mean Change From Baseline to Day 365 in White Blood Cells
timeFrame: Baseline (Day 1), Day 365
measure: OL; Mean Change From Baseline to Day 365 in Erythrocytes
timeFrame: Baseline (Day 1), Day 365
measure: OL; Mean Change From Baseline to Day 365 in Electrolytes
timeFrame: Baseline (Day 1), Day 365
measure: OL; Mean Change From Baseline to Day 365 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
timeFrame: Baseline (Day 1), Day 365
measure: OL; Mean Change From Baseline to Day 365 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
timeFrame: Baseline (Day 1), Day 365
measure: OL; Mean Change From Baseline to Day 729 in Hemoglobin, Total Protein, and Albumin
timeFrame: Baseline (Day 1), Day 729
measure: OL; Mean Change From Baseline to Day 729 in Platelets
timeFrame: Baseline (Day 1), Day 729
measure: OL; Mean Change From Baseline to Day 729 in Hematocrit
timeFrame: Baseline (Day 1), Day 729
measure: OL; Mean Change From Baseline to Day 729 in White Blood Cells
timeFrame: Baseline (Day 1), Day 729
measure: OL; Mean Change From Baseline to Day 729 in Erythrocytes
timeFrame: Baseline (Day 1), Day 729
measure: OL; Mean Change From Baseline to Day 729 in Electrolytes
timeFrame: Baseline (Day 1), Day 729
measure: OL; Mean Change From Baseline to Day 729 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
timeFrame: Baseline (Day 1), Day 729
measure: OL; Mean Change From Baseline to Day 729 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
timeFrame: Baseline (Day 1), Day 729
measure: OL; Mean Change From Baseline to Day 1121 in Hemoglobin, Total Protein, and Albumin
timeFrame: Baseline (Day 1), Day 1121
measure: OL; Mean Change From Baseline to Day 1121 in Platelets
timeFrame: Baseline (Day 1), Day 1121
measure: OL; Mean Change From Baseline to Day 1121 in Hematocrit
timeFrame: Baseline (Day 1), Day 1121
measure: OL; Mean Change From Baseline to Day 1121 in White Blood Cells
timeFrame: Baseline (Day 1), Day 1121
measure: OL; Mean Change From Baseline to Day 1121 in Erythrocytes
timeFrame: Baseline (Day 1), Day 1121
measure: OL; Mean Change From Baseline to Day 1121 in Electrolytes
timeFrame: Baseline (Day 1), Day 1121
measure: OL; Mean Change From Baseline to Day 1121 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
timeFrame: Baseline (Day 1), Day 1121
measure: OL; Mean Change From Baseline to Day 1121 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
timeFrame: Baseline (Day 1), Day 1121
measure: OL; Mean Change From Baseline to Day 1513 in Hemoglobin, Total Protein, and Albumin
timeFrame: Baseline (Day 1), Day 1513
measure: OL; Mean Change From Baseline to Day 1513 in Platelets
timeFrame: Baseline (Day 1), Day 1513
measure: OL; Mean Change From Baseline to Day 1513 in Hematocrit
timeFrame: Baseline (Day 1), Day 1513
measure: OL; Mean Change From Baseline to Day 1513 in White Blood Cells
timeFrame: Baseline (Day 1), Day 1513
measure: OL; Mean Change From Baseline to Day 1513 in Erythrocytes
timeFrame: Baseline (Day 1), Day 1513
measure: OL; Mean Change From Baseline to Day 1513 in Electrolytes
timeFrame: Baseline (Day 1), Day 1513
measure: OL; Mean Change From Baseline to Day 1513 in Bilirubin, Blood Urea Nitrogen, Creatinine, Calcium, Phosphorous, Serum Glucose, Fasting Serum Glucose, and Uric Acid
timeFrame: Baseline (Day 1), Day 1513
measure: OL; Mean Change From Baseline to Day 1513 in Alanine Aminotransferase, Aspartate Aminotransferase, G-Glutamyl Transferase, and Alkaline Phosphatase
timeFrame: Baseline (Day 1), Day 1513
measure: OL; Mean Systolic (SBP) and Diastolic (DBP) Blood Pressure During Open Label Period
timeFrame: Days 365, 729, 1121, and 1513
measure: OL; Mean Heart Rate (HR) During Open Label Period
timeFrame: Days 365, 729, 1121, and 1513
measure: OL; Mean Temperature (T) During Open Label Period
timeFrame: Days 365, 729, 1121, and 1513
Secondary outcomes:
measure: DB; Adjusted Mean Change From Baseline to Day 197 in DAS 28 Score (ESR) For INF Versus PLA (LOCF Analysis)
timeFrame: Baseline (Day 1), 6 months (Day 197)
measure: DB; DAS 28 (ESR) Area Under The Curve (AUC) Over 12 Months For ABA Versus INF
timeFrame: From Day 1 through Day 365 (12 months)
measure: DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 197
timeFrame: DB Day 197
measure: DB; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response at Day 365
timeFrame: DB Day 365
measure: DB; Adjusted Mean Change From Baseline to Day 197 in HAQ-DI (LOCF Analysis)
timeFrame: Baseline (Day 1), 6 months (Day 197)
measure: DB; Adjusted Mean Change From Baseline to Day 365 in HAQ-DI (LOCF Analysis)
timeFrame: Baseline (Day 1), 12 months (Day 365)
measure: DB; Adjusted Mean Change From Baseline to Day 197 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
timeFrame: Baseline (Day 1), 6 months (Day 197)
measure: DB; Adjusted Mean Change From Baseline to Day 365 in SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS)
timeFrame: Baseline (Day 1), 12 months (Day 365)
measure: DB; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) at Day 365
timeFrame: DB Day 365
measure: DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 197
timeFrame: DB Day 197
measure: DB; Percentage of Participants With American College of Rheumatology (ACR) Responses at Day 365
timeFrame: DB Day 365
measure: 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
timeFrame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
measure: DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 197
timeFrame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
measure: 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
timeFrame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
measure: 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
timeFrame: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
measure: DB; Number of Participants With AEs of Special Interest From Day 1 Through Day 365
timeFrame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
measure: DB; Number of Participants With AEs of Special Interest From Day 198 Through Day 365 in Participants Receiving Placebo Switched to Abatacept
timeFrame: From Day 198 through Day 365, and up to 56 days after last dose if occurring on-study
measure: DB; Number of Participants With Significant Changes in Mean Systolic and Diastolic Blood Pressure During Days 1 Through 197 and Days 1 Through 365
timeFrame: 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
measure: DB; Number of Participants With Significant Changes in Mean Heart Rate During Days 1 Through 197 and Days 1 Through 365
timeFrame: 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
measure: DB; Number of Participants With Significant Changes in Mean Temperature During Days 1 Through 197 and Days 1 Through 365
timeFrame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
measure: DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 197
timeFrame: From Baseline (Day 1) through Day 197, and up to 56 days after last dose if occurring on-study
measure: DB; Number of Participants With Select Hematologic and Blood Chemistry Laboratory Abnormalities on Days 1 Through 365
timeFrame: From Baseline (Day 1) through Day 365, and up to 56 days after last dose if occurring on-study
measure: DB; Number of Participants With Anti-Abatacept Antibodies From Day 1 Through Day 365 (Electrochemiluminescent [ECL] Immunoassay)
timeFrame: Day 1 through day 365
measure: DB; Percentage of Participants With Antibodies Against Infliximab (Human Anti-chimeric Antibody [HACA]) From Day 1 Through Day 365
timeFrame: Day 1 through day 365
measure: OL; Mean Change From Baseline Over Time in DAS 28 (ESR) Score
timeFrame: Baseline (Day 1), Day 365, Day 533, Day 729
measure: OL; Percentage of Participants With DAS28 (ESR) Remission and Low Disease Activity (LDAS) Over Time
timeFrame: Baseline (Day 1), Day 365, Day 533, Day 729
measure: OL; Percentage of Participants With Good, Moderate, or No Response According to European League Against Rheumatism (EULAR) Over Time
timeFrame: DB Days 365, 533, and 729
measure: OL; Percentage of Participants With American College of Rheumatology (ACR) Responses Over Time
timeFrame: DB Day 197, Day 365, Day 533, Day 729
measure: OL; Percentage of Participants Who Achieved Major Clinical Response
timeFrame: Defined from the date of achieving ACR 70 response to 6 months post response
measure: OL; Percentage of Participants With Clinically Meaningful Health Assessment Questionnaire-Disability Index (HAQ-DI) Response Over Time
timeFrame: OL Days 197, 253, 281, 309, 337, 365, 449, 533, 617, and 729
measure: OL; Adjusted Mean Change From Baseline to Day 729 in HAQ-DI
timeFrame: Day 1 (Baseline), Day 729
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Local Institution
state: Alabama
city: Denver
country: United States
facility: Local Institution
state: Colorado
city: Boca Raton
country: United States
facility: Local Institution
state: Florida
city: Ft Lauderdale
country: United States
facility: Local Institution
state: Florida
city: Largo
country: United States
facility: Local Institution
state: Florida
city: Indianapolis
country: United States
facility: Local Institution
state: Indiana
city: New Orleans
country: United States
facility: Local Institution
state: Louisiana
city: Springfield
country: United States
facility: Local Institution
state: Massachusetts
city: Worcester
country: United States
facility: Local Institution
state: Massachusetts
city: Flowood
country: United States
facility: Local Institution
state: Mississippi
city: Syracuse
country: United States
facility: Local Institution
state: New York
city: Charlotte
country: United States
facility: Local Institution
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution
state: Ohio
city: Oklahoma City
country: United States
facility: Local Institution
state: Oklahoma
city: Tulsa
country: United States
facility: Local Institution
state: Oklahoma
city: Bethlehem
country: United States
facility: Local Institution
state: Pennsylvania
city: Willow Grove
country: United States
facility: Local Institution
state: Pennsylvania
city: Austin
country: United States
facility: Local Institution
state: Texas
city: Dallas
country: United States
facility: Local Institution
state: Texas
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordoba
country: Argentina
facility: Local Institution
city: Tucuman
country: Argentina
facility: Local Institution
city: Cairns
country: Australia
facility: Local Institution
state: Queensland
city: Cotton Tree
country: Australia
facility: Local Institution
state: Queensland
city: Clayton
country: Australia
facility: Local Institution
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution
state: Victoria
city: Malvern
country: Australia
facility: Local Institution
state: Victoria
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Recife
country: Brazil
facility: Local Institution
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: St. Johns
country: Canada
facility: Local Institution
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Local Institution
state: Ontario
city: Kitchener
country: Canada
facility: Local Institution
state: Ontario
city: Ottawa
country: Canada
facility: Local Institution
state: Ontario
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Ste-Foy
country: Canada
facility: Local Institution
state: Quebec
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Kitchener
country: Canada
facility: Local Institution
city: Prague 2
country: Czech Republic
facility: Local Institution
city: Copenhagen
country: Denmark
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Tijuana
country: Mexico
facility: Local Institution
state: Baja California
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Leon
country: Mexico
facility: Local Institution
state: Guanajuato
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: San Luis Potosi
country: Mexico
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Sopot
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Rio Piedras
country: Puerto Rico
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Muckleneuk
country: South Africa
facility: Local Institution
state: Gauteng
city: Berea
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Panorama
country: South Africa
facility: Local Institution
state: Western Cape
city: A Coruna
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Cordoba
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Falun
country: Sweden
facility: Local Institution
city: Linkoping
country: Sweden
facility: Local Institution
city: Lund
country: Sweden
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
city: Uppsala
country: Sweden
facility: Local Institution
city: Bern
country: Switzerland
facility: Local Institution
city: St. Gallen
country: Switzerland
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Schiff M, Keiserman M, Codding C, Songcharoen S, Berman A, Nayiager S, Saldate C, Li T, Aranda R, Becker JC, Lin C, Cornet PL, Dougados M. Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate. Ann Rheum Dis. 2008 Aug;67(8):1096-103. doi: 10.1136/ard.2007.080002. Epub 2007 Nov 29.