Clinical trial NCT00929864: Abatacept Versus Adalimumab Head-to-Head
Official title: A Randomized, Head-to-Head, Single-Blind Study to Compare the Efficacy and Safety of Subcutaneous Abatacept Versus Subcutaneous Adalimumab, Both With Background Methotrexate, in Biologic-Naive Subjects With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2009-06-30
Enrollment: 869
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 study is demonstrate that subcutaneous abatacept is non-inferior (no worse than) to subcutaneous adalimumab in the treatment of subjects with rheumatoid arthritis who are biologic naive


Eligibility criteria: Inclusion Criteria:

* Moderate to severe Rheumatoid arthritis (RA) according to American College of Rheumatology (ACR) criteria
* Methotrexate failure
* Naive to RA biologics
* ≤5 years duration of disease
* Disease Activity Score-28 C-reactive protein (DAS28 CRP) ≥ 3.2
* Willingness to self-inject subcutaneous (SC) drug

Exclusion Criteria:

* Previous or current medical conditions that are warnings against the use of tumor necrosis factor (TNF)-blocking agents
* History of active or chronic hepatitis
* Cancer in the last 5 years
* History of severe chronic or recurrent bacterial or viral infections
* Risk of tuberculosis
* Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematologic, Gastro-intestinal, pulmonary, cardiac, neurologic, or cerebral disease

Primary outcomes:
measure: The Proportion of Participants Meeting the American College of Rheumatology (ACR) Criteria of 20% Improvement (ACR20) After 12 Months of Treatment - Intent to Treat Population
timeFrame: Day 1 to Day 365
Secondary outcomes:
measure: Proportion of Participants With Local Injection Site Reactions Adverse Events (Pre-specified) Reported During 12 Month Period - ITT Population
timeFrame: Day 1 to 12 Months
measure: Incidence Rate of Local Injection Site Reactions (Pre-specified) Reported During 24 Month Period - ITT Population
timeFrame: Day 1 to Day 729
measure: Proportion of Participants Without Radiographic Progression in Total Score Less Than or Equal to the Smallest Detectable Change (SDC) From Baseline to Months 12 and 24 Using Modified Van Der Heijde Total Sharp Score (mSvdHS) - ITT Population
timeFrame: Baseline to Day 729
measure: Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 12 Months of Treatment - ITT Population
timeFrame: Day 1 to Day 365
measure: Incidence Rate of Serious Adverse Events (SAEs), Serious Infections, Pre-specified Opportunistic Infections, and Discontinuation for Any Cause at 24 Months of Treatment - ITT Population
timeFrame: Day 1 to Day 729
measure: Proportion of Participants With Induction of Autoantibodies During the 12 Months and 24 Months Periods - ITT Population
timeFrame: Day 1 to Day 729
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Rheumatology Associates, Pc
state: Alabama
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Tuscaloosa
country: United States
facility: Clinical And Translational Research Center Of Alabama, Pc
state: Alabama
city: Peoria
country: United States
facility: Sun Valley Arthritis Center, Ltd.
state: Arizona
city: Hot Springs
country: United States
facility: Mercy Clinic Hot Springs Communities
state: Arkansas
city: Huntington Beach
country: United States
facility: Talbert Medical Group
state: California
city: La Jolla
country: United States
facility: Allergy & Rheumatology Medical Clinic, Inc.
state: California
city: Long Beach
country: United States
facility: Valerius Med Group & Res Ctr Of Greater Long Beach, Inc.
state: California
city: Pasadena
country: United States
facility: Irene Y. Tong
state: California
city: San Diego
country: United States
facility: San Diego Arthritis Medical Clinic
state: California
city: Torrance
country: United States
facility: Healthcare Partners Medical Group
state: California
city: Torrance
country: United States
facility: Drs. Goldin, Nies, Klashman & Eng
state: California
city: Upland
country: United States
facility: Inland Rheumatology & Osteoporosis Medical Group
state: California
city: Aventura
country: United States
facility: Arthritis And Rheumatic Disease Specialties
state: Florida
city: Gainesville
country: United States
facility: University Of Florida College Of Medicine At Jacksonville
state: Florida
city: Miami
country: United States
facility: Center For Arthritis And Rheumatic Diseases
state: Florida
city: Palm Harbor
country: United States
facility: Arthritis Research Of Florida, Inc.
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Research Center
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates
state: Florida
city: Venice
country: United States
facility: Lovelace Scientific Resources, Inc
state: Florida
city: Atlanta
country: United States
facility: Arthritis & Rheumatology Of Georgia
state: Georgia
city: Atlanta
country: United States
facility: Laureate Clinical Research Group
state: Georgia
city: Gainesville
country: United States
facility: Arthritis Center Of North Georgia
state: Georgia
city: Boise
country: United States
facility: St. Luke'S Clinic - Rheumatology
state: Idaho
city: Coeur D Alene
country: United States
facility: Coeur D'Alene Arthrit Clin
state: Idaho
city: Quincy
country: United States
facility: Quincy Medical Group
state: Illinois
city: Rockford
country: United States
facility: Rockford Orthopedic Associates, Ltd.
state: Illinois
city: Cedar Rapids
country: United States
facility: Physicians Clinic Of Iowa
state: Iowa
city: Elizabethtown
country: United States
facility: Center For Arthritis And Osteoporosis
state: Kentucky
city: Lexington
country: United States
facility: Bluegrass Community Research, Inc.
state: Kentucky
city: Cumberland
country: United States
facility: Klein And Associates, M.D., Pa
state: Maryland
city: Wheaton
country: United States
facility: The Center For Rheumatology And Bone Research
state: Maryland
city: Boston
country: United States
facility: Brigham And Women'S Hospital
state: Massachusetts
city: Mansfield
country: United States
facility: Mansfield Health Center
state: Massachusetts
city: Battle Creek
country: United States
facility: Associated Internal Medicine Specialists
state: Michigan
city: Kalamazoo
country: United States
facility: Rheumatology Pc
state: Michigan
city: Jackson
country: United States
facility: Arthritis Associates Of Mississippi
state: Mississippi
city: St.Louis
country: United States
facility: Physician Groups, Lc Dba
state: Missouri
city: Reno
country: United States
facility: Arthritis Center Of Reno
state: Nevada
city: Dover
country: United States
facility: Seacoast Arthritis And Osteoporosis Center
state: New Hampshire
city: Nashua
country: United States
facility: Nashua Rheumatology
state: New Hampshire
city: Las Cruces
country: United States
facility: Arthritis And Osteoporosis Associates Of New Mexico
state: New Mexico
city: Lake Success
country: United States
facility: North Shore Lij Health System
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Smithtown
country: United States
facility: Rheumatology Associates Of Long Island
state: New York
city: Asheville
country: United States
facility: Asheville Rheumatology & Osteoporosis Research Asso P. A.
state: North Carolina
city: Statesville
country: United States
facility: Carolina Pharmaceutical Research
state: North Carolina
city: Oklahoma City
country: United States
facility: Health Research Of Oklahoma
state: Oklahoma
city: Oklahoma City
country: United States
facility: Health Research Institute
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Sciences Institute
state: Oklahoma
city: Bethlehem
country: United States
facility: East Penn Rheumatology Associates, P.C.
state: Pennsylvania
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Center Of Reading, Llp
state: Pennsylvania
city: Charleston
country: United States
facility: Low Country Rheumatology, Pa
state: South Carolina
city: Columbia
country: United States
facility: Columbia Arthritis Center, P.A.
state: South Carolina
city: Austin
country: United States
facility: Lovelace Scientific Resources, Inc.
state: Texas
city: Dallas
country: United States
facility: Arthritis Centers Of Texas
state: Texas
city: Houston
country: United States
facility: Rheumatic Disease Clinical Research Center, Llc
state: Texas
city: Chesapeake
country: United States
facility: Center For Arthritis & Rheumatic Diseases, Pc
state: Virginia
city: Spokane
country: United States
facility: Rockwood Research Center
state: Washington
city: Clarksburg
country: United States
facility: Mountain State Clinical Research
state: West Virginia
city: Glendale
country: United States
facility: Rheumatic Disease Center
state: Wisconsin
city: Ciudad Autonoma De Beunos Aire
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad Autonoma De Buenos Aire
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad Autonoma De Buenos Aire
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ciudad Autonoma
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Cordoba, Crd
country: Argentina
facility: Local Institution
state: Cordoba
city: Rosario
country: Argentina
facility: Local Institution
state: Santa Fe
city: San Miguel De Tucuman
country: Argentina
facility: Local Institution
state: Tucuman
city: Cordoba
country: Argentina
facility: Local Institution
city: San Juan
country: Argentina
facility: Local Institution
city: Tucuman
country: Argentina
facility: Local Institution
city: Winnipeg
country: Canada
facility: Local Institution
state: Manitoba
city: Hamilton
country: Canada
facility: Local Institution
state: Ontario
city: Trois-Rivieres
country: Canada
facility: Local Institution
state: Quebec
city: Quebec
country: Canada
facility: Local Institution
city: Santiago
country: Chile
facility: Local Institution
state: Providencia
city: Bellavista
country: Peru
facility: Local Institution
state: Callao 2
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Jabado O, Maldonado MA, Schiff M, Weinblatt ME, Fleischmann R, Robinson WH, He A, Patel V, Greenfield A, Saini J, Galbraith D, Connolly SE. Differential Changes in ACPA Fine Specificity and Gene Expression in a Randomized Trial of Abatacept and Adalimumab in Rheumatoid Arthritis. Rheumatol Ther. 2022 Apr;9(2):391-409. doi: 10.1007/s40744-021-00404-x. Epub 2021 Dec 8.
citation: Keystone EC, Ahmad HA, Yazici Y, Bergman MJ. Disease activity measures at baseline predict structural damage progression: data from the randomized, controlled AMPLE and AVERT trials. Rheumatology (Oxford). 2020 Aug 1;59(8):2090-2098. doi: 10.1093/rheumatology/kez455.
citation: Fleischmann R, Weinblatt M, Ahmad H, Maldonado MA, Alemao E, Ye J, Schiff M. Efficacy of Abatacept and Adalimumab in Patients with Early Rheumatoid Arthritis With Multiple Poor Prognostic Factors: Post Hoc Analysis of a Randomized Controlled Clinical Trial (AMPLE). Rheumatol Ther. 2019 Dec;6(4):559-571. doi: 10.1007/s40744-019-00174-7. Epub 2019 Oct 22.
citation: Fleischmann R, Connolly SE, Maldonado MA, Schiff M. Brief Report: Estimating Disease Activity Using Multi-Biomarker Disease Activity Scores in Rheumatoid Arthritis Patients Treated With Abatacept or Adalimumab. Arthritis Rheumatol. 2016 Sep;68(9):2083-9. doi: 10.1002/art.39714.
citation: Schiff M, Weinblatt ME, Valente R, Citera G, Maldonado M, Massarotti E, Yazici Y, Fleischmann R. Reductions in disease activity in the AMPLE trial: clinical response by baseline disease duration. RMD Open. 2016 Apr 19;2(1):e000210. doi: 10.1136/rmdopen-2015-000210. eCollection 2016.
citation: Fleischmann R, Weinblatt ME, Schiff M, Khanna D, Maldonado MA, Nadkarni A, Furst DE. Patient-Reported Outcomes From a Two-Year Head-to-Head Comparison of Subcutaneous Abatacept and Adalimumab for Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2016 Jul;68(7):907-13. doi: 10.1002/acr.22763.
citation: Sokolove J, Schiff M, Fleischmann R, Weinblatt ME, Connolly SE, Johnsen A, Zhu J, Maldonado MA, Patel S, Robinson WH. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial. Ann Rheum Dis. 2016 Apr;75(4):709-14. doi: 10.1136/annrheumdis-2015-207942. Epub 2015 Sep 10.
citation: Schiff M, Weinblatt ME, Valente R, van der Heijde D, Citera G, Elegbe A, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial. Ann Rheum Dis. 2014 Jan;73(1):86-94. doi: 10.1136/annrheumdis-2013-203843. Epub 2013 Aug 20.
citation: Weinblatt ME, Schiff M, Valente R, van der Heijde D, Citera G, Zhao C, Maldonado M, Fleischmann R. Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis: findings of a phase IIIb, multinational, prospective, randomized study. Arthritis Rheum. 2013 Jan;65(1):28-38. doi: 10.1002/art.37711.