Clinical trial NCT00048581: Phase III Study of BMS-188667 (CTLA4Ig) in Patients With Rheumatoid Arthritis Who Are Currently Failing Anti-TNF Therapy or Who Have Failed Anti-TNF Therapy in the Past.
Official title: A Phase III, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-188667 in Subjects With Active Rheumatoid Arthritis on Background Disease Modifying Anti-Rheumatic Drugs (DMARDS) Who Have Failed Anti-Tumor Necrosis Factor (TNF) Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2002-11-13
Enrollment: 738
Sex: ALL
Minimum age (years): 18
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 determine whether abatacept treatment on a background of Disease Modifying Antirheumatic Drugs (DMARDs) will relieve the symptoms of rheumatoid arthritis (RA) in participants who are currently receiving anti-tumor necrosis factor (TNF) therapy for at least 3 months and are not responding or have taken anti-TNF therapy in the last 3 months and did not respond. The safety of treatment with abatacept will also be evaluated. This study also has a 4.5-year long-term extension beginning 6 months after the start of the study.


Eligibility criteria: Eligibility Criteria:

* Active rheumatoid arthritis currently failing anti-TNF therapy or have failed anti-TNF therapy in the past.

Exclusion Criteria:

* Women who are pregnant or breast feeding
* Current symptoms of serious medical disease
* History of cancer in last 5 years other than non-melanoma skin cancer
* Chronic serious infection
* Active TB requiring treatment in last 5 years
* Herpes zoster in last 2 months
* Any active viral infection including Human Immunodeficiency Virus (HIV)
* Serious side effects associated with previous anti-TNF therapy

Primary outcomes:
measure: Double-blind Period (DB); Number of Participants With American College of Rheumatology (ACR) 20 Response at Day 169
timeFrame: Day 169
measure: DB; Number of Participants Achieving Clinically Meaningful Improvement in Health Assessment Questionnaire (HAQ)
timeFrame: Day 169
measure: Open-Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation
timeFrame: From first day of OL to 5.5 years
measure: OL; Number of Participants AEs of Special Interest
timeFrame: From first day of OL to 5.5 years
measure: OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria
timeFrame: From first day of OL to 5.5 years
measure: OL; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality Criteria
timeFrame: From first day of OL to 5.5 years
measure: OL; Mean Time-matched Baseline Immunoglobulin (Ig) Levels Over the OL
timeFrame: Baseline and Days 169, 365, 729, and 1093
measure: OL; Mean Time-matched Change From Baseline in Immunoglobulin (Ig) Levels Over the OL
timeFrame: BL, Days 169, 365, 729, and 1093
Secondary outcomes:
measure: DB; Number of Participants With ACR 20, ACR 50, and ACR 70 Responses Over Time
timeFrame: Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Time-matched Baseline Tender Joint Counts (TJCs) and Post-Baseline TJCs Over Time: ACR Core Component
timeFrame: BL
measure: DB; Mean Time-Matched Percentage of Change From Baseline in TJC Over Time: ACR Core Component
timeFrame: BL, Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Time-matched Baseline Swollen Joint Count (SJC) and Post-Baseline SJCs Over Time: ACR Core Component
timeFrame: Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Time-Matched Percentage of Change From Baseline in SJC Over Time: ACR Core Component
timeFrame: Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Time-matched Baseline Participant Pain Assessment Over Time: ACR Core Component
timeFrame: BL
measure: DB; Mean Time-Matched Percentage of Change From Baseline in Participant Pain Assessment Over Time: ACR Core Component
timeFrame: BL, Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Time-matched Baseline HAQ-DI Over Time: ACR Core Component
timeFrame: BL
measure: DB; Mean Time-Matched Percentage of Change From Baseline in HAQ-DI Over Time: ACR Core Component
timeFrame: BL, Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Time-matched Baseline Participant Global Assessment Over Time: ACR Core Component
timeFrame: BL
measure: DB; Mean Time-Matched Percentage of Change From Baseline in Participant Global Assessment Over Time: ACR Core Component
timeFrame: BL, Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Time-matched Baseline Physician Global Assessment Over Time: ACR Core Component
timeFrame: BL
measure: DB; Mean Time-Matched Percentage of Change From Baseline in Physician Global Assessment Over Time: ACR Core Component
timeFrame: BL, Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Time-matched Baseline C-Reactive Protein (CRP) Levels Over Time: ACR Core Component
timeFrame: BL
measure: DB; Mean Time-Matched Percentage of Change From Baseline in CRP Levels Over Time: ACR Core Component
timeFrame: Days 15, 29, 57, 85, 113, 141, and 169
measure: DB; Mean Baseline Levels of Disease Biomarkers (Interleukin-6 (IL-6), Soluble IL-2 Receptor [sIL-2R], and Tumor Necrosing Factor [TNF]-Alpha) in Participants With Measurements at Day 169
timeFrame: BL
measure: DB; Mean Change From Baseline to Day 169 in Levels of Disease Biomarkers (IL-6, sIL-2R, and TNF-alpha) in Participants With Measurements at Day 169
timeFrame: BL, Day 169
measure: DB; Mean Baseline Levels of Disease Biomarkers (E-Selectin, Soluble Inter-Cellular Adhesion Molecule 1 [sICAM-1], and Matrix Metalloproteinase-3 [MMP-3]) in Participants With Measurements at Day 169
timeFrame: BL
measure: DB; Mean Change From Baseline to Day 169 in Levels of Disease Biomarkers (E-Selectin, sICAM-1, and MMP-3) in Participants With Measurements at Day 169
timeFrame: BL, Day 169
measure: DB; Mean Change From Baseline to Day 169 in Rheumatoid Factor (RF) Status
timeFrame: BL, Day 169
measure: DB; Mean Baseline Short Form 36 (SF-36) Quality of Life Physical Component Summary (PCS), Mental Component Summary (MCS), and SF-36 Individual Component Scores For Participants With Measurements at Day 85
timeFrame: BL
measure: DB; Adjusted Mean Change From Baseline to Day 85 in Short SF-36 PCS, MCS, and SF-36 Individual Component Scores
timeFrame: BL, Day 85
measure: DB; Mean Baseline SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participants With Measurements at Day 169
timeFrame: BL
measure: DB; Adjusted Mean Change From Baseline to Day 169 in SF-36 PCS, MCS, and SF-36 Individual Component Scores For Participants With Measurements at Day 169
timeFrame: BL, Day 169
measure: DB; Mean Baseline HAQ-DI and HAQ Component Scores in Participants With Assessments at Day 169
timeFrame: BL
measure: DB; Adjusted Mean Change From Baseline to Day 169 in HAQ-DI and HAQ Component Scores in Participants With Assessments at Day 169
timeFrame: BL, Day 169
measure: DB; Mean Disease Activity Score (DAS)28 (C-Reactive Protein [CRP]) and Mean Disease Activity Score (Erythrocyte Sedimentation Rate [ESR]) at Day 169
timeFrame: BL, Day 169
measure: DB; Adjusted Mean Change From Baseline to Day 169 in DAS28 (CRP) and DAS28 (ESR)
timeFrame: BL, Day 169
measure: DB; Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs, Related AEs, or AEs Leading to Discontinuation
timeFrame: From BL up to database lock for DB period (6/2/2004)
measure: DB; Number of Participants AEs of Special Interest
timeFrame: From BL up to database lock for DB period (6/2/2004)
measure: DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality (MA) Criteria
timeFrame: From BL up to database lock for DB period (6/2/2004)
measure: DB; Number of Participants With Blood Chemistry Laboratories Meeting MA Criteria
timeFrame: From BL up to database lock for DB period (6/2/2004)
measure: DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA)
timeFrame: From BL to Day 169
measure: OL; Number of Participants With ACR 20, ACR 50, and ACR 70 Responses Over Time For Participants Treated in the OL
timeFrame: Days 15, 29, 57, 85, 113, 141, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821
measure: OL; Number of Participants With Low Disease Activity (LDAS) or Remission For Participants Treated in the OL
timeFrame: Days 15, 29, 57, 85, 113, 141, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821
measure: OL; Mean Time-matched Baseline DAS28 (CRP) Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in DAS28 (CRP) Over Time For Participants Treated in the OL
timeFrame: BL, Days 15, 29, 57, 85, 113, 141, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821
measure: OL; Mean Time-matched Baseline DAS28 (ESR) Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in DAS28 (ESR) Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821
measure: OL; Number of Participants Achieving HAQ Response Over Time In Participants Treated in the OL
timeFrame: Days 15, 29, 57, 85, 113, 141, 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821
measure: OL; Mean Time-matched Baseline HAQ-DI and HAQ Component Scores Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in HAQ-DI and HAQ Component Scores For Participants Treated in the OL
timeFrame: BL, Days 169, 253, 365, 449, 533, 617, 729, 813, 897, 981, 1093, 1261, 1457, 1625, and 1821
measure: OL; Mean Time-matched Baseline Levels of Rheumatoid Factor (RF) Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Levels of RF Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1261, 1457, and 1821
measure: OL; Mean Time-matched Baseline Levels of C-Reactive Protein (CRP) Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Levels of CRP Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1261, 1457, and 1821
measure: OL; Mean Time-matched Baseline Erythrocyte Sedimentation Rate (ESR) Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in ESR Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1261, 1457, and 1821
measure: OL; Mean Time-matched Baseline Levels of Soluble Interleukin 2 Receptor (sIL-2R) Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Levels of sIL-2R Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1261, 1457, and 1821
measure: OL; Mean Time-matched Baseline SF-36 PCS and MCS Over Time For Participants Treated in OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in SF-36 PCS and MCS Over Time For Participants Treated in OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Physical Function Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Physical Function Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Role-Physical Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Role-Physical Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Bodily Pain Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Bodily Pain Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline General Health Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in General Health Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Vitality Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Vitality Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Social Functioning Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Social Functioning Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Role-Emotional Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Role-Emotional Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Mental Health Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Mental Health Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Medical Outcomes Study Sleep Module (MOS-sleep) Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in MOS-Sleep Score Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Fatigue Visual Analog Score (VAS) Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Time-matched Change From Baseline in Fatigue VAS Over Time For Participants Treated in the OL
timeFrame: BL, Days 169, 365, 729, 1093, 1457, and 1821
measure: OL; Mean Time-matched Baseline Activity Limitation Score Over Time For Participants Treated in the OL
timeFrame: BL
measure: OL; Mean Change From Baseline in Activity Limitation Score Over Time For Participants Treated in the OL
timeFrame: Days 169, 365, 729, 1093, 1457, and 1821
measure: Cumulative Analysis (DB + OL); Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbent Assay (ELISA)
timeFrame: From BL (Day 1) to Day 1821
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution
state: Alabama
city: Mobile
country: United States
facility: Local Institution
state: Alabama
city: Paradise Valley
country: United States
facility: Local Institution
state: Arizona
city: La Jolla
country: United States
facility: Local Institution
state: California
city: Long Beach
country: United States
facility: Local Institution
state: California
city: Palo Alto
country: United States
facility: Local Institution
state: California
city: Rancho Mirage
country: United States
facility: Local Institution
state: California
city: Denver
country: United States
facility: Local Institution
state: Colorado
city: Englewood
country: United States
facility: Local Institution
state: Colorado
city: Bridgeport
country: United States
facility: Local Institution
state: Connecticut
city: Hamden
country: United States
facility: Local Institution
state: Connecticut
city: Clearwater
country: United States
facility: Local Institution
state: Florida
city: Fort Lauderdale
country: United States
facility: Local Institution
state: Florida
city: Largo
country: United States
facility: Local Institution
state: Florida
city: Palm Harbor
country: United States
facility: Local Institution
state: Florida
city: Tampa
country: United States
facility: Local Institution
state: Florida
city: Rome
country: United States
facility: Local Institution
state: Georgia
city: Indianapolis
country: United States
facility: Local Institution
state: Indiana
city: Wichita
country: United States
facility: Local Institution
state: Kansas
city: New Orleans
country: United States
facility: Local Institution
state: Louisiana
city: Boston
country: United States
facility: Local Institution
state: Massachusetts
city: Springfield
country: United States
facility: Local Institution
state: Massachusetts
city: Lincoln
country: United States
facility: Local Institution
state: Nebraska
city: New Brunswick
country: United States
facility: Local Institution
state: New Jersey
city: Albany
country: United States
facility: Local Institution
state: New York
city: Syracuse
country: United States
facility: Local Institution
state: New York
city: Charlotte
country: United States
facility: Local Institution
state: North Carolina
city: Hickory
country: United States
facility: Local Institution
state: North Carolina
city: Bismarck
country: United States
facility: Local Institution
state: North Dakota
city: Cincinnati
country: United States
facility: Local Institution
state: Ohio
city: Oklahoma City
country: United States
facility: Local Institution
state: Oklahoma
city: Eugene
country: United States
facility: Local Institution
state: Oregon
city: Portland
country: United States
facility: Local Institution
state: Oregon
city: Duncansville
country: United States
facility: Local Institution
state: Pennsylvania
city: Norristown
country: United States
facility: Local Institution
state: Pennsylvania
city: Sellersville
country: United States
facility: Local Institution
state: Pennsylvania
city: Willow Grove
country: United States
facility: Local Institution
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution
state: South Carolina
city: Austin
country: United States
facility: Local Institution
state: Texas
city: Dallas
country: United States
facility: Local Institution
state: Texas
city: Vancouver
country: United States
facility: Local Institution
state: Washington
city: Milwaukee
country: United States
facility: Local Institution
state: Wisconsin
Study officials:
References:
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: Stewart AL and Ware JE. Measuring function and well being. The Medical Outcomes Study Approach. Durham, NC: Duke University Press. 1992.
citation: Spritzer KL, Hays RD. (2003, November). MOS Sleep Scale: A Manual For Use and Scoring, Version 1.0. Los Angeles, CA.
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.