Methotrexate-Inadequate Response Study
A Phase IIIB Multicenter, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Abatacept Administered Subcutaneously and Intravenously in Subjects With Rheumatoid Arthritis, Receiving Background Methotrexate, and Experiencing an Inadequate Response to Methotrexate
2 other identifiers
interventional
2,492
24 countries
203
Brief Summary
The purpose of this study is to determine whether a weekly subcutaneous dose of abatacept yields clinical efficacy comparable to that of monthly intravenous doses of abatacept in participants with rheumatoid arthritis and an inadequate response to current methotrexate therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2008
Longer than P75 for phase_3
203 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 15, 2007
CompletedFirst Posted
Study publicly available on registry
November 16, 2007
CompletedStudy Start
First participant enrolled
January 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2009
CompletedResults Posted
Study results publicly available
July 6, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2014
CompletedNovember 9, 2015
November 1, 2015
1.8 years
November 15, 2007
April 29, 2011
November 5, 2015
Conditions
Outcome Measures
Primary Outcomes (2)
Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169
The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, 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).
Day 169
Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population
Serum samples from all treated adult participants with active rheumatoid arthritis who were from the Anti-TNF failure population were screened for the presence of drug-specific antibodies using Enzyme Linked Immunoabsorbant Assay (ELISA). The number of participants who had the presence of anti-abatacept antibodies or anti-CTLA-4 antibodies present in their serum are summarized.
Days 85, and 169 and postvisits on Days 28, 56, and 85
Secondary Outcomes (31)
Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169
Day 169
Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169
Day 169
Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI
Baseline to Day 169
Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169
Day 169
Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation
Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.
- +26 more secondary outcomes
Study Arms (2)
Subcutaneous (SC) Abatacept
ACTIVE COMPARATORParticipants received 125 mg weekly SC abatacept injections (with an intravenous \[IV\] abatacept loading dose on Day 1, based on weight). A double-dummy design was used to protect the blind, thus, participants also received IV injections of placebo (IV Placebo) with the exception that on Day 1 a loading dose of IV abatacept replaced the IV Placebo treatment.
Intravenous (IV) Abatacept
ACTIVE COMPARATORParticipants received IV abatacept infusions on Days 1, 15, 29, and every 28 days, thereafter. A double-dummy design was used to protect the blind, thus, participants also received SC injections of placebo (SC Placebo).
Interventions
Participants received 125 mg weekly SC abatacept injections (with an intravenous \[IV\] abatacept loading dose on Day 1, based on weight). A double-dummy design was used to protect the blind, thus, participants also received IV injections of placebo (IV Placebo) with the exception that on Day 1 a loading dose of IV abatacept replaced the IV Placebo treatment.
Participants received IV abatacept infusions on Days 1, 15, 29, and every 28 days, thereafter. A double-dummy design was used to protect the blind, thus, participants also received SC injections of placebo (SC Placebo). 500mg (for body weight up to 60 kg) 750 mg (body weight between 61 and 100 kg) 1g (body weight above 100 kg)infusions
Eligibility Criteria
You may qualify if:
- Subjects who are considered methotrexate inadequate responders
- or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)
You may not qualify if:
- Subjects who failed one or multiple anti-tumor necrosis factor (TNF) therapies
- Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematous)
- Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)
- Subjects with severe chronic or recurrent bacterial infections
- Subjects who have received treatment with rituximab
- An Anti-TNF Failure Sub-study was initiated (recruited separately from Main study) using the same treatment as the Main study in order to assess the immunogenicity and safety in the Anti-TNF Failure population. The Sub-study terminated due to low recruitment and participants were permitted to roll into the LT Open Label Period.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (203)
Rheumatology Associates, Pc
Birmingham, Alabama, 35205, United States
Coastal Clinical Research, Inc
Mobile, Alabama, 36608, United States
Advanced Arthritis Care & Research
Scottsdale, Arizona, 85258, United States
Catalina Pointe Clinical Research, Inc.
Tucson, Arizona, 85704, United States
St. Joseph'S Mercy Clinic
Hot Springs, Arkansas, 71913, United States
Talbert Medical Group
Huntington Beach, California, 92646, United States
Allergy & Rheumatology Medical Clinic, Inc.
La Jolla, California, 92037, United States
Valerius Medical Group &Research Ctr. Of Greater Long Beach
Long Beach, California, 90806, United States
Stanford University School Of Medicine
Palo Alto, California, 94304, United States
San Diego Arthritis Medical Clinic
San Diego, California, 92108, United States
Boulder Medical Center
Boulder, Colorado, 80304, United States
Arthritis Assoc And Osteo Ctr Of Col Sprgs
Colorado Springs, Colorado, 80910, United States
Denver Arthritis Clinic
Denver, Colorado, 80230, United States
Arthritis Center Of The Rockies, Pc
Loveland, Colorado, 80538, United States
Guadagnoli, Germano
Bridgeport, Connecticut, 06606, United States
Joao Nascimento
Bridgeport, Connecticut, 06606, United States
Clinical Research Center Of Ct/Ny
Danbury, Connecticut, 06810, United States
Arthritis And Rheumatic Disease Specialties
Aventura, Florida, 33180, United States
Arthritis & Osteoporosis Treatment Center, Pa
Orange Park, Florida, 32073, United States
Rheumatology Associates Of Central Florida
Orlando, Florida, 32806, United States
The Arthritis Center
Palm Harbor, Florida, 34684, United States
Sarasota Arthritis Research Center
Sarasota, Florida, 34239, United States
Arthritis & Rheumatology Of Georgia,Pc
Atlanta, Georgia, 30342, United States
Boise Rheumatology/ Intermountain Research Center, Inc
Boise, Idaho, 83702, United States
Coeur D'Alene Arthrit Clin
Coeur d'Alene, Idaho, 83814, United States
Quincy Medical Group
Quincy, Illinois, 62301, United States
Rockford Orthopedic Associates, Ltd.
Rockford, Illinois, 61107, United States
The Arthritis Center
Springfield, Illinois, 62704, United States
Klein And Associates, M.D., Pa
Cumberland, Maryland, 21502, United States
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01610, United States
Shores Rheumatology, P. C.
Saint Clair Shores, Michigan, 48081, United States
Arthritis Assoicates Of Mississippi
Jackson, Mississippi, 39202, United States
Kansas City Internal Medicine
Lee's Summit, Missouri, 64086, United States
Physician Research Collaboration, Llc
Lincoln, Nebraska, 68516, United States
Allergy And Arthritis Associates
Dover, New Jersey, 07801, United States
Albuquerque Clinical Trials, Inc.
Albuquerque, New Mexico, 87102, United States
Albuquerque Rehabilitation & Rheumatology Pc
Albuquerque, New Mexico, 87102, United States
The Center For Rheumatology, Llp
Albany, New York, 12206, United States
Southern Tier Arthritis & Rheumatism
Olean, New York, 14760, United States
Arthritis Health Associates
Syracuse, New York, 13210, United States
Asheville Rheumatology & Osteoporosis Research Asso P. A.
Asheville, North Carolina, 28801, United States
The Arthritis Clinic & Carolina Bone & Joint
Charlotte, North Carolina, 28210, United States
Rheumatology
Durham, North Carolina, 27704, United States
Physicians East, Pa
Greenville, North Carolina, 27834, United States
Carolina Pharmaceutical Research
Statesville, North Carolina, 28625, United States
Carolina Arthritis Associates
Wilmington, North Carolina, 28401, United States
Cincinnati Rheumatic Disease Study Group
Cincinnati, Ohio, 45219, United States
Health Research Of Oklahoma
Oklahoma City, Oklahoma, 73103, United States
Oklahoma Center For Arthritis Therapy And Research
Tulsa, Oklahoma, 74104, United States
Healthcare Research Consultants
Tulsa, Oklahoma, 74135, United States
Pro Research
Eugene, Oregon, 97401, United States
Portland Rheumatology Clinic, Llc
Lake Oswego, Oregon, 97035, United States
East Penn Rheumatology Associates
Bethlehem, Pennsylvania, 18015, United States
Rheumatology Associates
Providence, Rhode Island, 02906, United States
Low Country Rheumatology, Pa
Charleston, South Carolina, 29406, United States
Columbia Arthritis Center
Columbia, South Carolina, 29204, United States
Carolina Health Specialists
Myrtle Beach, South Carolina, 29572, United States
Acme Research, Llc
Orangeburg, South Carolina, 29118, United States
Arthritis Clinic
Jackson, Tennessee, 38305, United States
Rheumatology Consultants Pllc
Knoxville, Tennessee, 37909, United States
The Arthritis Group, Pc
Memphis, Tennessee, 38104, United States
St. Thomas Hospital Tower East
Nashville, Tennessee, 37205, United States
Walter F. Chase
Austin, Texas, 78705, United States
Rheumatic Disease Clinical Research Center, Llc
Houston, Texas, 77004, United States
Accurate Clinical Research
Houston, Texas, 77034, United States
Texas Research Center
Sugarland, Texas, 77479, United States
Arthritis Clinic Of Northern Virginia, P.C.
Arlington, Virginia, 22205, United States
Center For Arthritis & Rheumatic Diseases, Pc
Chesapeake, Virginia, 23320, United States
South Puget Sound Clinincal Research Center
Olympia, Washington, 98502, United States
Tacoma Center For Arthritis Research Ps
Tacoma, Washington, 98405, United States
Local Institution
Buenos Aires, Buenos Aires, 1015, Argentina
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Buenos Aires, Buenos Aires, 1426, Argentina
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Buenos Aires, Buenos Aires, C1428DQG, Argentina
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Ciudad Autonoma, Buenos Aires, CP1425A WC, Argentina
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Córdoba, Córdoba Province, 5000, Argentina
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Córdoba, Córdoba Province, 5016, Argentina
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Rosario, Santa Fe, Santa Fe Province, 2000, Argentina
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Santa Fe, Santa Fe Province, 3000, Argentina
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San Miguel de Tucumán, Tucumán Province, 4000, Argentina
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St Leonards, New South Wales, 2065, Australia
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Cairns, Queensland, QLD 4870, Australia
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Maroochydore, Queensland, 4558, Australia
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Woodville, South Australia, 5011, Australia
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Heidelberg, Victoria, 3081, Australia
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Shenton Park, Western Australia, 6008, Australia
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Brussels, 1020, Belgium
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Brussels, 1200, Belgium
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Hasselt, 3500, Belgium
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Leuven, 3000, Belgium
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Wilrijk, 2610, Belgium
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Yvoir, 5530, Belgium
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Goiânia, Goiás, 74110, Brazil
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Goiânia, Goiás, 74605, Brazil
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Juiz de Fora, Minas Gerais, 36010, Brazil
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Curitiba, Paraná, 80060240, Brazil
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Curitiba, Paraná, 80440, Brazil
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Recife, Pernambuco, 50670, Brazil
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Rio de Janeiro, Rio de Janeiro, 20551, Brazil
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Porto Alegre, Rio Grande do Sul, 90035003, Brazil
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Porto Alegre, Rio Grande do Sul, 91610, Brazil
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Campinas, São Paulo, 13059, Brazil
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Campinas, São Paulo, 13083, Brazil
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São Paulo, São Paulo, 04027, Brazil
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Winnipeg, Manitoba, R3A 1M3, Canada
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St. John's, Newfoundland and Labrador, A1A 5E8, Canada
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Hamilton, Ontario, L8N 1Y2, Canada
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Hamilton, Ontario, L8N 2B6, Canada
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Mississauga, Ontario, L5M 2V8, Canada
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Ottawa, Ontario, K1H 1A2, Canada
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Ste-Foy, Quebec, G1V 3M7, Canada
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Ste-Foy, Quebec, G1W 4R4, Canada
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Trois-Rivières, Quebec, G8Z 1Y2, Canada
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Saskatoon, Saskatchewan, S7N 0W8, Canada
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Santiago, Santiago Metropolitan, 0, Chile
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Santiago, Santiago Metropolitan, 7500995, Chile
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Santiago, Santiago Metropolitan, Chile
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Bordeaux, 33076, France
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Brest, 29609, France
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Chambray-lès-Tours, 37170, France
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Le Mans, 72037, France
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Lille, 59037, France
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Marseille, 13008, France
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Nice, 06202, France
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Paris, 75651, France
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Paris, 75679, France
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Poitiers, 86021, France
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Strasbourg, 67098, France
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Berlin, 14059, Germany
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Leipzig, 04103, Germany
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München, 80639, Germany
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München, 81541, Germany
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Heraklion Crete, 71110, Greece
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Budapest, 1023, Hungary
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Debrecen, 4012, Hungary
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Secunderabad, Andhra Pradesh, 500003, India
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Navrangpura, Ahmedabad, Gujarat, 380009, India
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Bangalore, Karnataka, 560 034, India
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Bangalore, 560003, India
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Hyderabad, 500004, India
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Lucknow, 226014, India
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New Delhi, 110029, India
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Dublin, Dublin, 4, Ireland
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Napoli, 80131, Italy
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Padua, 35128, Italy
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Pavia, 27100, Italy
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Roma, 00168, Italy
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Siena, 53100, Italy
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Aguascalientes, Aguascalientes, 20230, Mexico
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Chihuahua City, Chihuahua, 31000, Mexico
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Tijuana, Estado de Baja California, 22320, Mexico
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Guadalajara, Jalisco, 0, Mexico
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Guadalajara, Jalisco, 44100, Mexico
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Guadalajara, Jalisco, 44620, Mexico
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Guadalajara, Jalisco, 44690, Mexico
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Mexico City, Mexico City, 06726, Mexico
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Morelia, Michioacan, 58270, Mexico
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Nuevo León, Nuevo León, 64020, Mexico
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Querétaro City, Querétaro, 76178, Mexico
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San Luis Potosí City, San Luis Potosí, 78240, Mexico
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Mérida, Yucatán, 97000, Mexico
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Leeuwarden, 8934 AD, Netherlands
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Lima, Lima Province, 11, Peru
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Lima, Lima Province, LIMA 13, Peru
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Lima, Lima Province, LIMA 27, Peru
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Lima, Lima Province, LIMA 33, Peru
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Callao, Provincia Constitucional del Callao, CALLAO 2, Peru
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Bialystok, 15-337, Poland
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Bialystok, 15-461, Poland
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Bydgoszcz, 85-168, Poland
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Gmina Końskie, 26-200, Poland
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Krakow, 30-510, Poland
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Poznan, 60-218, Poland
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Poznan, 60773, Poland
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Torun, 87-100, Poland
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Warsaw, 02-777, Poland
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Moscow, 115522, Russia
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Moscow, 119049, Russia
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Moscow, 129327, Russia
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Yaroslavl, 150003, Russia
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Yekaterinburg, 620102, Russia
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Kempton Park, Gauteng, 1619, South Africa
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Muckleneuk, Gauteng, 0002, South Africa
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Muckleneuk, Gauteng, 0132, South Africa
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Pretoria, Gauteng, 0083, South Africa
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Durban, KwaZulu-Natal, 4001, South Africa
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Panorama, Western Cape, 7500, South Africa
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Seoul, Sungdong-Gu, 133-792, South Korea
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Daegu, 705-718, South Korea
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Daejeon, 302-799, South Korea
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Seoul, 135-710, South Korea
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Seoul, 137-040, South Korea
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Kaohsiung City, 833, Taiwan
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Taichung, 402, Taiwan
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Taichung, 404, Taiwan
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Taichung, 407, Taiwan
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Denizli, 20070, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Gaziantep, 27310, Turkey (Türkiye)
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Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom
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Bridgend, Glamorgan, CF31 1RQ, United Kingdom
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London, Greater London, E11 1NR, United Kingdom
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Southampton, Hampshire, SO16 6YD, United Kingdom
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Newcastle upon Tyne, Tyne and Wear, NE7 7DN, United Kingdom
Related Publications (3)
Alten R, Bingham CO 3rd, Cohen SB, Curtis JR, Kelly S, Wong D, Genovese MC. Antibody response to pneumococcal and influenza vaccination in patients with rheumatoid arthritis receiving abatacept. BMC Musculoskelet Disord. 2016 May 26;17:231. doi: 10.1186/s12891-016-1082-z.
PMID: 27229685DERIVEDGenovese MC, Tena CP, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, Nash P, Simon-Campos JA, Box J, Legerton CW 3rd, Nasonov E, Durez P, Delaet I, Teng J, Alten R. Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial. J Rheumatol. 2014 Apr;41(4):629-39. doi: 10.3899/jrheum.130112. Epub 2014 Mar 1.
PMID: 24584926DERIVEDGenovese MC, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, Nash P, Simon-Campos JA, Porawska W, Box J, Legerton C 3rd, Nasonov E, Durez P, Aranda R, Pappu R, Delaet I, Teng J, Alten R. Subcutaneous abatacept versus intravenous abatacept: a phase IIIb noninferiority study in patients with an inadequate response to methotrexate. Arthritis Rheum. 2011 Oct;63(10):2854-64. doi: 10.1002/art.30463.
PMID: 21618201DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- BMS Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 15, 2007
First Posted
November 16, 2007
Study Start
January 1, 2008
Primary Completion
November 1, 2009
Study Completion
September 1, 2014
Last Updated
November 9, 2015
Results First Posted
July 6, 2011
Record last verified: 2015-11