Clinical trial NCT00124982: Study of Abatacept (BMS-188667) in Subjects With Active Rheumatoid Arthritis on Background Non-biologic DMARDS (Disease Modifying Antirheumatic Drugs) Who Have an Inadequate Response to Anti-TNF Therapy
Official title: A Phase III, Multi-Center, Open Label Study to Evaluate the Efficacy, Tolerability and Safety of Abatacept (BMS-188667) in Subjects With Active Rheumatoid Arthritis on Background Non-Biologic DMARDs Who Have an Inadequate Response to Anti-TNF Therapy and Have Limited Therapeutic Options
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-07-29
Enrollment: 1286
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to summarize the safety and tolerability of abatacept during 6 months of combined treatment with one or more of the background non-biologic disease modifying anti-rheumatic drugs (DMARDs) approved for rheumatoid arthritis (RA) in subjects with active RA. Secondary objectives assessed the clinical efficacy of combination treatment, including disease activity, physical function, and quality of life outcomes.


Eligibility criteria: Inclusion Criteria:

* Completed double-blind portion of the IM101064 study.
* Rheumatoid arthritis (RA) for greater than 1 year from the time of initial diagnosis
* American College of Rheumatology (ACR) functional class I, II, III
* Subjects currently or previously received an anti-TNF therapy at an approved labeled dose for at least 3 months

Exclusion Criteria:

* Subjects with active vasculitis of a major organ system (except subcutaneous rheumatoid nodules)
* History of cancer within the last 5 years (other than non-melanoma skin cell cancers cured by local resection)

Primary outcomes:
measure: Short-term Period: Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuations, AEs, Related AEs, or AEs Leading to Discontinuations
timeFrame: Days 1-169
measure: Short-term Period: Number of Participants With AEs of Special Interest
timeFrame: Days 1-169
measure: Short-term Period: Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria
timeFrame: Days 1-169
measure: Short-term Period: Number of Participants With Liver and Kidney Function Laboratories Meeting MA Criteria
timeFrame: Days 1-169
measure: Short-term Period: Number of Participants With Electrolyte Laboratories Meeting MA Criteria
timeFrame: Days 1-169
measure: Short-term Period: Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria
timeFrame: Days 1-169
measure: Short-term Period: Mean Change From Baseline in Systolic and Diastolic Blood Pressure
timeFrame: Day 1 (Baseline) -Day 169
measure: Short-term Period: Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)
timeFrame: Days 1-169
measure: Long-term Period: Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuations, AEs, Related AEs, or AEs Leading to Discontinuations
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Number of Participants With AEs of Special Interest
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Number of Participants With Liver and Kidney Function Laboratories Meeting MA Criteria
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Number of Participants With Electrolyte Laboratories Meeting MA Criteria
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Change From Baseline in Hemoglobin (HGB), Total Protein, and Albumin Over Time
timeFrame: BL, Day 365, Day 729
measure: Long-term Period: Change From Baseline in Hematocrit Over Time
timeFrame: BL, Day 365, Day 729
measure: Long-term Period: Change From Baseline in Erythrocytes Over Time
timeFrame: BL, Day 365, Day 729
measure: Long-term Period: Change From Baseline in Platelets (PLT) Over Time
timeFrame: BL, Day 365, Day 729
measure: Long-term Period: Change From Baseline in White Blood Cells Over Time
timeFrame: BL, Day 365, Day 729
measure: Long-term Period: Change From Baseline in Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and G-Glutamyl Transferase (GGT) Over Time
timeFrame: BL, Day 365, Day 729
measure: Long-term Period: Change From Baseline in Bilirubin, Blood Urea Nitrogen (BUN), Creatinine, Calcium (Ca), Phosphorus (P), Serum Glucose (Glu), and Uric Acid Over Time
timeFrame: BL, Day 365, Day 729
measure: LT; Change From Baseline in Sodium (Na), Potassium (K), Chloride (Cl) Over Time
timeFrame: BL, Day 365, Day 729
measure: Long-term Period: Mean Sitting Systolic Blood Pressure (SBP) Over Time
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Mean Sitting Diastolic Blood Pressure (DBP) Over Time
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Mean Heart Rate (HR) Over Time
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
measure: Long-term Period: Mean Temperature (T) Over Time
timeFrame: From Day 169 through Day 813, including up to 56 days after the last dose of long-term period abatacept
Secondary outcomes:
measure: Short-term Period: Number of Participants With Clinically Meaningful Improvement (CMI) in Disease Activity Score (DAS 28), Low Disease Activity (LDAS), or Remission at Day 169
timeFrame: BL, Day 169
measure: Short-term Period: Mean Time-matched Baseline (Day 0) DAS 28 and DAS 28 for Post-Baseline Visits Through 6 Month Open-Label
timeFrame: BL (Day 0), Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169
measure: Short-term Period: Mean Time-matched Change From Baseline (Day 0) in DAS 28 Through 6 Month Open-Label
timeFrame: BL (Day 0), Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169
measure: Short-term Period: Mean Change From Baseline to Day 169 in High Sensitivity C-Reactive Protein (Hs-CRP)
timeFrame: BL, Day 169
measure: Short-term Period: Mean Change From Baseline to Day 169 in Rheumatoid Factor (RF)
timeFrame: BL, Day 169
measure: Short-term Period: Mean Change From Baseline to Day 169 in the Health Assessment Questionnaire Disability Index (HAQ-DI)
timeFrame: BL, Day 169
measure: Short-term Period: Number of Participants Achieving a Clinically Meaningful HAQ Response
timeFrame: BL, Day 169
measure: Short-term Period: Mean Baseline Short Form 36 (SF-36) Quality of Life Physical Component Summary (PCS), Mental Component Summary (MCS), and SF-36 Individual Component Scores
timeFrame: BL
measure: Short-term Period: Mean Change From Baseline to Day 169 in SF-36 PCS, MCS, and SF-36 Individual Component Scores
timeFrame: BL, Day 169
measure: Short-term Period: Mean Baseline Fatigue Visual Analog Scale (VAS)
timeFrame: BL
measure: Short-term Period: Mean Change From Baseline to Day 169 in Fatigue Visual Analog Scale (VAS)
timeFrame: BL, Day 169
measure: Long-term Period: Number of Participants With Clinically Meaningful Improvement in DAS 28, Low Disease Activity, or Remission Over Time
timeFrame: BL, Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Baseline (Day 0) DAS 28 and DAS 28 for Post-Baseline Visits Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Change From Baseline (Day 0) in DAS 28 Over The Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Baseline (Day 0) Number of Tender Joints and Number of Tender Joints for Post-Baseline Visits Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Change From Baseline (Day 0) in Number of Tender Joints Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Baseline (Day 0) Number of Swollen Joints And Post-Baseline Number of Swollen Joints Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-Matched Change From Baseline (Day 0) in Number of Swollen Joints Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Baseline (Day 0) Hs-CRP Levels and Hs-CRP Levels for Post-Baseline Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Change From Baseline (Day 0) in Hs-CRP Level Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Baseline (Day 0) Visual Analog Scale (VAS) and VAS for Post-Baseline Visits Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Change From Baseline (Day 0) in VAS Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Baseline (Day 0) HAQ-DI and HAQ-DI Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term
timeFrame: BL (Day 0)
measure: Long-term Period: Mean HAQ-DI and HAQ-DI Component Scores For Participant Cohorts at Post-baseline Visits Over the Long Term
timeFrame: Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Change From Baseline (Day 0) in HAQ-DI and HAQ-DI Components For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term
timeFrame: BL (Day 0), Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Number of Participants Achieving Clinically Meaningful HAQ Response Over Time
timeFrame: BL, Days 365, 449, 533, 617, 729, 813
measure: Long-term Period: Mean Time-matched Baseline (Day 0) SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term
timeFrame: BL (Day 0)
measure: Long-term Period: Mean SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Post-baseline Visits Over the Long Term
timeFrame: Days 365 and 729
measure: Long-term Period: Mean Time-matched Change From Baseline (Day 0) in SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participant Cohorts at Each Corresponding Post-baseline Visit Over the Long Term
timeFrame: BL (Day 0), Days 365, 729
measure: LT; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA
timeFrame: Days 1-813
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution
state: Alabama
city: Huntsville
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state: Alabama
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city: Tucson
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state: Arizona
city: Long Beach
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state: California
city: Palm Springs
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state: California
city: Palo Alto
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facility: Local Institution
state: California
city: San Diego
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state: California
city: Santa Monica
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state: California
city: Colorado Springs
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facility: Local Institution
state: Colorado
city: Denver
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state: Colorado
city: Danbury
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state: Connecticut
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state: Connecticut
city: Trumbull
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state: Connecticut
city: Washington
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state: District of Columbia
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state: Florida
city: Clearwater
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state: Florida
city: Ft. Lauderdale
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state: Florida
city: Jupiter
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state: Florida
city: Largo
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state: Florida
city: Sarasota
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state: Florida
city: Atlanta
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state: Georgia
city: Blue Ridge
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state: Georgia
city: Macon
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state: Georgia
city: Morton Grove
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state: Illinois
city: Evansville
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state: Indiana
city: Indianapolis
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state: Indiana
city: Des Moines
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facility: Local Institution
state: Iowa
city: Kansas City
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state: Kansas
city: Prairie Village
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state: Kansas
city: Bowling Green
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state: Kentucky
city: Louisville
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state: Kentucky
city: New Orleans
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state: Louisiana
city: Boston
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state: Massachusetts
city: Peabody
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state: Massachusetts
city: Springfield
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state: Massachusetts
city: Worcester
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city: Ann Arbor
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state: Michigan
city: East Lansing
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city: Voorhees
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city: Albany
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state: New York
city: Brooklyn
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state: New York
city: Hewlett
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state: New York
city: Lake Success
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facility: Local Institution
state: New York
city: Mineola
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facility: Local Institution
state: New York
city: New York
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facility: Local Institution
state: New York
city: Olean
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facility: Local Institution
state: New York
city: Orchard Park
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state: New York
city: Rochester
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state: New York
city: Schenectady
country: United States
facility: Local Institution
state: New York
city: Smithtown
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state: New York
city: Syracuse
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state: New York
city: Asheville
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state: North Carolina
city: Charlotte
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state: North Carolina
city: Hickory
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state: North Carolina
city: Wilmington
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city: Beachwood
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facility: Local Institution
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city: Cleveland
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city: Columbus
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city: Mayfield Village
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city: Youngstown
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facility: Local Institution
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city: Bethlehem
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facility: Local Institution
state: Pennsylvania
city: Camp Hill
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facility: Local Institution
state: Pennsylvania
city: Duncansville
country: United States
facility: Local Institution
state: Pennsylvania
city: Erie
country: United States
facility: Local Institution
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city: Meadville
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facility: Local Institution
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city: Philadelphia
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facility: Local Institution
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city: Pittsburgh
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facility: Local Institution
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city: West Reading
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facility: Local Institution
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city: Wexford
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facility: Local Institution
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city: Willow Grove
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facility: Local Institution
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city: Providence
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facility: Local Institution
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city: Myrtle Beach
country: United States
facility: Local Institution
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city: Simpsonville
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facility: Local Institution
state: South Carolina
city: Sioux Falls
country: United States
facility: Local Institution
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city: Hixson
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facility: Local Institution
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city: Knoxville
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facility: Local Institution
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city: Austin
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facility: Local Institution
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city: Corpus Christi
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facility: Local Institution
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city: Dallas
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facility: Local Institution
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city: Houston
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facility: Local Institution
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city: Lubbock
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facility: Local Institution
state: Texas
city: San Antonio
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facility: Local Institution
state: Texas
city: Sugarland
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facility: Local Institution
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city: Burke
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facility: Local Institution
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city: Chesapeake
country: United States
facility: Local Institution
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city: Fairfax
country: United States
facility: Local Institution
state: Virginia
city: Salem
country: United States
facility: Local Institution
state: Virginia
city: Seattle
country: United States
facility: Local Institution
state: Washington
city: Vancouver
country: United States
facility: Local Institution
state: Washington
city: Glendale
country: United States
facility: Local Institution
state: Wisconsin
city: La Crosse
country: United States
facility: Local Institution
state: Wisconsin
city: Madison
country: United States
facility: Local Institution
state: Wisconsin
city: Bruxelles
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Prague 2
country: Czech Republic
facility: Local Institution
city: Boisguillaume
country: France
facility: Local Institution
city: Bordeaux Cedex
country: France
facility: Local Institution
city: Brest Cedex
country: France
facility: Local Institution
city: Chambray Les Tours
country: France
facility: Local Institution
city: Montpellier
country: France
facility: Local Institution
city: Nice Cedex 03
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Rennes Cedex 9
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Toulouse
country: France
facility: Local Institution
city: Freiburg
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Kiel
country: Germany
facility: Local Institution
city: Leipzig
country: Germany
facility: Local Institution
city: Tuebingen
country: Germany
facility: Local Institution
city: Cork
country: Ireland
facility: Local Institution
city: Genova
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Torino
country: Italy
facility: Local Institution
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Distrito Federal
country: Mexico
facility: Local Institution
city: Alicante
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Guipuzcoa
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Santander
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Cambridge
country: United Kingdom
facility: Local Institution
state: Cambridgeshire
city: Manchester
country: United Kingdom
facility: Local Institution
state: Greater Manchester
city: Maidstone
country: United Kingdom
facility: Local Institution
state: Kent
city: Leeds
country: United Kingdom
facility: Local Institution
state: North Yorkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Schiff M, Pritchard C, Huffstutter JE, Rodriguez-Valverde V, Durez P, Zhou X, Li T, Bahrt K, Kelly S, Le Bars M, Genovese MC. The 6-month safety and efficacy of abatacept in patients with rheumatoid arthritis who underwent a washout after anti-tumour necrosis factor therapy or were directly switched to abatacept: the ARRIVE trial. Ann Rheum Dis. 2009 Nov;68(11):1708-14. doi: 10.1136/ard.2008.099218. Epub 2008 Dec 15.
citation: Alten R, Burkhardt H, Feist E, Kruger K, Rech J, Rubbert-Roth A, Voll RE, Elbez Y, Rauch C. Abatacept used in combination with non-methotrexate disease-modifying antirheumatic drugs: a descriptive analysis of data from interventional trials and the real-world setting. Arthritis Res Ther. 2018 Jan 2;20(1):1. doi: 10.1186/s13075-017-1488-5.
citation: Vieira MC, Zwillich SH, Jansen JP, Smiechowski B, Spurden D, Wallenstein GV. Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results From a Network Meta-analysis. Clin Ther. 2016 Dec;38(12):2628-2641.e5. doi: 10.1016/j.clinthera.2016.11.004. Epub 2016 Nov 24.
citation: Hassett AL, Li T, Buyske S, Savage SV, Gignac MA. The multi-faceted assessment of independence in patients with rheumatoid arthritis: preliminary validation from the ATTAIN study. Curr Med Res Opin. 2008 May;24(5):1443-53. doi: 10.1185/030079908x297376. Epub 2008 Apr 9.
citation: Genovese MC, Schiff M, Luggen M, Becker JC, Aranda R, Teng J, Li T, Schmidely N, Le Bars M, Dougados M. Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy. Ann Rheum Dis. 2008 Apr;67(4):547-54. doi: 10.1136/ard.2007.074773. Epub 2007 Oct 5.