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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: Subcutaneous (SC) Abatacept; Drug: Intravenous (IV) Abatacept

• Study Type: Interventional
• Enrollment (Actual): 2492
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1426
    • Local Institution
  • Buenos Aires, Argentina, 1015
    • Local Institution
  • Buenos Aires, Argentina, C1428DQG
    • Local Institution
  • Cordoba, Argentina, 5000
    • Local Institution
  • Cordoba, Argentina, 5016
    • Local Institution
  • Santa Fe, Argentina, 3000
    • Local Institution
  • Tucuman, Argentina, 4000
    • Local Institution
  • Buenos Aires
    • Ciudad Autonoma, Buenos Aires, Argentina, CP1425A WC
      • Local Institution
  • Santa Fe
    • Rosario, Santa Fe, Santa Fe, Argentina, 2000
      • Local Institution
• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Local Institution
  • Queensland
    • Cairns, Queensland, Australia, QLD 4870
      • Local Institution
    • Maroochydore, Queensland, Australia, 4558
      • Local Institution
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Local Institution
  • Victoria
    • Heidelberg, Victoria, Australia, 3081
      • Local Institution
  • Western Australia
    • Shenton Park, Western Australia, Australia, 6008
      • Local Institution
• Belgium
  • Bruxelles, Belgium, 1200
    • Local Institution
  • Bruxelles, Belgium, 1020
    • Local Institution
  • Hasselt, Belgium, 3500
    • Local Institution
  • Leuven, Belgium, 3000
    • Local Institution
  • Wilrijk, Belgium, 2610
    • Local Institution
  • Yvoir, Belgium, 5530
    • Local Institution
• Brazil
  • Rio De Janeiro, Brazil, 20551
    • Local Institution
  • Sao Paulo, Brazil, 04027
    • Local Institution
  • Goias
    • Goiania, Goias, Brazil, 74110
      • Local Institution
    • Goiania, Goias, Brazil, 74605
      • Local Institution
  • Minas Gerais
    • Juiz De Fora, Minas Gerais, Brazil, 36010
      • Local Institution
  • Parana
    • Curitiba, Parana, Brazil, 80440
      • Local Institution
    • Curitiba, Parana, Brazil, 80060240
      • Local Institution
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50670
      • Local Institution
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 91610
      • Local Institution
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035003
      • Local Institution
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083
      • Local Institution
    • Campinas, Sao Paulo, Brazil, 13059
      • Local Institution
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M3
      • Local Institution
  • Newfoundland and Labrador
    • St. John'S, Newfoundland and Labrador, Canada, A1A 5E8
      • Local Institution
  • Ontario
    • Hamilton, Ontario, Canada, L8N 1Y2
      • Local Institution
    • Hamilton, Ontario, Canada, L8N 2B6
      • Local Institution
    • Mississauga, Ontario, Canada, L5M 2V8
      • Local Institution
    • Ottawa, Ontario, Canada, K1H 1A2
      • Local Institution
  • Quebec
    • Ste-Foy, Quebec, Canada, G1V 3M7
      • Local Institution
    • Ste-Foy, Quebec, Canada, G1W 4R4
      • Local Institution
    • Trois-Rivieres, Quebec, Canada, G8Z 1Y2
      • Local Institution
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Local Institution
• Chile
  • Metropolitana
    • Santiago, Metropolitana, Chile
      • Local Institution
    • Santiago, Metropolitana, Chile, 7500995
      • Local Institution
    • Santiago De Chile, Metropolitana, Chile
      • Local Institution
    • Santiago De Chile, Metropolitana, Chile
      • Local Institution
• France
  • Bordeaux Cedex, France, 33076
    • Local Institution
  • Brest Cedex, France, 29609
    • Local Institution
  • Chambray Les Tours, France, 37170
    • Local Institution
  • Le Mans, France, 72037
    • Local Institution
  • Lille Cedex, France, 59037
    • Local Institution
  • Marseille, France, 13008
    • Local Institution
  • Nice Cedex 3, France, 06202
    • Local Institution
  • Paris Cedex 13, France, 75651
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
  • Poitiers, France, 86021
    • Local Institution
  • Strasbourg Cedex, France, 67098
    • Local Institution
• Germany
  • Berlin, Germany, 14059
    • Local Institution
  • Leipzig, Germany, 04103
    • Local Institution
  • Muenchen, Germany, 81541
    • Local Institution
  • Munchen, Germany, 80639
    • Local Institution
• Greece
  • Heraklion Crete, Greece, 71110
    • Local Institution
• Hungary
  • Budapest, Hungary, 1023
    • Local Institution
  • Debrecen, Hungary, 4012
    • Local Institution
• India
  • Bangalore, India, 560003
    • Local Institution
  • Hyderabad, India, 500004
    • Local Institution
  • Lucknow, India, 226014
    • Local Institution
  • New Delhi, India, 110029
    • Local Institution
  • Andhra Pradesh
    • Secunderabad, Andhra Pradesh, India, 500003
      • Local Institution
  • Gujarat
    • Navrangpura, Ahmedabad, Gujarat, India, 380009
      • Local Institution
  • Karnataka
    • Bangalore, Karnataka, India, 560 034
      • Local Institution
• Ireland
  • Dublin, Ireland, 4
    • Local Institution
• Italy
  • Napoli, Italy, 80131
    • Local Institution
  • Padova, Italy, 35128
    • Local Institution
  • Pavia, Italy, 27100
    • Local Institution
  • Roma, Italy, 00168
    • Local Institution
  • Siena, Italy, 53100
    • Local Institution
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-718
    • Local Institution
  • Daejeon, Korea, Republic of, 302-799
    • Local Institution
  • Seoul, Korea, Republic of, 135-710
    • Local Institution
  • Seoul, Korea, Republic of, 137-040
    • Local Institution
  • Sungdong-Gu
    • Seoul, Sungdong-Gu, Korea, Republic of, 133-792
      • Local Institution
• Mexico
  • Aguascalientes, Mexico, 20230
    • Local Institution
  • Chihuahua, Mexico, 31000
    • Local Institution
  • Nuevo Leon, Mexico, 64020
    • Local Institution
  • Queretaro, Mexico, 76178
    • Local Institution
  • San Luis Potosi, Mexico, 78240
    • Local Institution
  • Baja California
    • Tijuana, Baja California, Mexico, 22320
      • Local Institution
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 06726
      • Local Institution
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • Local Institution
    • Guadalajara, Jalisco, Mexico, 44690
      • Local Institution
    • Guadalajara, Jalisco, Mexico
      • Local Institution
    • Guadalajara, Jalisco, Mexico, 44620
      • Local Institution
  • Michioacan
    • Morelia, Michioacan, Mexico, 58270
      • Local Institution
  • Yucatan
    • Merida, Yucatan, Mexico, 97000
      • Local Institution
• Netherlands
  • Leeuwarden, Netherlands, 8934 AD
    • Local Institution
• Peru
  • Callao, Peru, CALLAO 2
    • Local Institution
  • Lima, Peru, LIMA 13
    • Local Institution
  • Lima, Peru, LIMA 33
    • Local Institution
  • Lima, Peru, 11
    • Local Institution
  • Lima, Peru, LIMA 27
    • Local Institution
• Poland
  • Bialystok, Poland, 15-337
    • Local Institution
  • Bialystok, Poland, 15-461
    • Local Institution
  • Bydgoszcz, Poland, 85-168
    • Local Institution
  • Konskie, Poland, 26-200
    • Local Institution
  • Krakow, Poland, 30-510
    • Local Institution
  • Poznan, Poland, 60-218
    • Local Institution
  • Poznan, Poland, 60773
    • Local Institution
  • Torun, Poland, 87-100
    • Local Institution
  • Warszawa, Poland, 02-777
    • Local Institution
• Russian Federation
  • Ekaterinburg, Russian Federation, 620102
    • Local Institution
  • Moscow, Russian Federation, 115522
    • Local Institution
  • Moscow, Russian Federation, 129327
    • Local Institution
  • Moscow, Russian Federation, 119049
    • Local Institution
  • Yaroslavl, Russian Federation, 150003
    • Local Institution
• South Africa
  • Gauteng
    • Kempton Park, Gauteng, South Africa, 1619
      • Local Institution
    • Muckleneuk, Gauteng, South Africa, 0002
      • Local Institution
    • Muckleneuk, Gauteng, South Africa, 0132
      • Local Institution
    • Pretoria, Gauteng, South Africa, 0083
      • Local Institution
  • Kwa Zulu Natal
    • Durban, Kwa Zulu Natal, South Africa, 4001
      • Local Institution
  • Western Cape
    • Panorama, Western Cape, South Africa, 7500
      • Local Institution
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Local Institution
  • Taichung, Taiwan, 404
    • Local Institution
  • Taichung, Taiwan, 402
    • Local Institution
  • Taichung, Taiwan, 407
    • Local Institution
• Turkey
  • Denizli, Turkey, 20070
    • Local Institution
  • Edirne, Turkey, 22030
    • Local Institution
  • Gaziantep, Turkey, 27310
    • Local Institution
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 2QQ
      • Local Institution
  • Glamorgan
    • Bridgend, Glamorgan, United Kingdom, CF31 1RQ
      • Local Institution
  • Greater London
    • London, Greater London, United Kingdom, E11 1NR
      • Local Institution
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Local Institution
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
      • Local Institution
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Rheumatology Associates, Pc
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Advanced Arthritis Care & Research
    • Tucson, Arizona, United States, 85704
      • Catalina Pointe Clinical Research, Inc.
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • St. Joseph'S Mercy Clinic
  • California
    • Huntington Beach, California, United States, 92646
      • Talbert Medical Group
    • La Jolla, California, United States, 92037
      • Allergy & Rheumatology Medical Clinic, Inc.
    • Long Beach, California, United States, 90806
      • Valerius Medical Group &Research Ctr. Of Greater Long Beach
    • Palo Alto, California, United States, 94304
      • Stanford University School of Medicine
    • San Diego, California, United States, 92108
      • San Diego Arthritis Medical Clinic
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Boulder Medical Center
    • Colorado Springs, Colorado, United States, 80910
      • Arthritis Assoc And Osteo Ctr Of Col Sprgs
    • Denver, Colorado, United States, 80230
      • Denver Arthritis Clinic
    • Loveland, Colorado, United States, 80538
      • Arthritis Center Of The Rockies, Pc
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Joao Nascimento
    • Bridgeport, Connecticut, United States, 06606
      • Guadagnoli, Germano
    • Danbury, Connecticut, United States, 06810
      • Clinical Research Center of CT/NY
  • Florida
    • Aventura, Florida, United States, 33180
      • Arthritis and Rheumatic Disease Specialties
    • Orange Park, Florida, United States, 32073
      • Arthritis & Osteoporosis Treatment Center, PA
    • Orlando, Florida, United States, 32806
      • Rheumatology Associates of Central Florida
    • Palm Harbor, Florida, United States, 34684
      • The Arthritis Center
    • Sarasota, Florida, United States, 34239
      • Sarasota Arthritis Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Arthritis & Rheumatology Of Georgia,Pc
  • Idaho
    • Boise, Idaho, United States, 83702
      • Boise Rheumatology/ Intermountain Research Center, Inc
    • Coeur D Alene, Idaho, United States, 83814
      • Coeur D'Alene Arthrit Clin
  • Illinois
    • Quincy, Illinois, United States, 62301
      • Quincy Medical Group
    • Rockford, Illinois, United States, 61107
      • Rockford Orthopedic Associates, Ltd.
    • Springfield, Illinois, United States, 62704
      • The Arthritis Center
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Klein And Associates, M.D., Pa
  • Massachusetts
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • St. Clair Shores, Michigan, United States, 48081
      • Shores Rheumatology, P. C.
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Arthritis Assoicates Of Mississippi
  • Missouri
    • Lee'S Summit, Missouri, United States, 64086
      • Kansas City Internal Medicine
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Physician Research Collaboration, LLC
  • New Jersey
    • Dover, New Jersey, United States, 07801
      • Allergy and Arthritis Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Rehabilitation & Rheumatology Pc
  • New York
    • Albany, New York, United States, 12206
      • The Center For Rheumatology, Llp
    • Olean, New York, United States, 14760
      • Southern Tier Arthritis & Rheumatism
    • Syracuse, New York, United States, 13210
      • Arthritis Health Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Rheumatology & Osteoporosis Research Asso P. A.
    • Charlotte, North Carolina, United States, 28210
      • The Arthritis Clinic & Carolina Bone & Joint
    • Durham, North Carolina, United States, 27704
      • Rheumatology
    • Greenville, North Carolina, United States, 27834
      • Physicians East, PA
    • Statesville, North Carolina, United States, 28625
      • Carolina Pharmaceutical Research
    • Wilmington, North Carolina, United States, 28401
      • Carolina Arthritis Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Cincinnati Rheumatic Disease Study Group
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • Healthcare Research Consultants
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma Center For Arthritis Therapy And Research
  • Oregon
    • Eugene, Oregon, United States, 97401
      • PRO Research
    • Lake Oswego, Oregon, United States, 97035
      • Portland Rheumatology Clinic, Llc
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • East Penn Rheumatology Associates
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Rheumatology Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology, PA
    • Columbia, South Carolina, United States, 29204
      • Columbia Arthritis Center
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Health Specialists
    • Orangeburg, South Carolina, United States, 29118
      • Acme Research, Llc
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Arthritis Clinic
    • Knoxville, Tennessee, United States, 37909
      • Rheumatology Consultants Pllc
    • Memphis, Tennessee, United States, 38104
      • The Arthritis Group, Pc
    • Nashville, Tennessee, United States, 37205
      • St. Thomas Hospital Tower East
  • Texas
    • Austin, Texas, United States, 78705
      • Walter F. Chase
    • Houston, Texas, United States, 77004
      • Rheumatic Disease Clinical Research Center, LLC
    • Houston, Texas, United States, 77034
      • Accurate Clinical Research
    • Sugarland, Texas, United States, 77479
      • Texas Research Center
  • Virginia
    • Arlington, Virginia, United States, 22205
      • Arthritis Clinic Of Northern Virginia, P.C.
    • Chesapeake, Virginia, United States, 23320
      • Center For Arthritis & Rheumatic Diseases, Pc
  • Washington
    • Olympia, Washington, United States, 98502
      • South Puget Sound Clinincal Research Center
    • Tacoma, Washington, United States, 98405
      • Tacoma Center For Arthritis Research Ps

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Subjects who are considered methotrexate inadequate responders
• 10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Subcutaneous (SC) Abatacept; 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.	Drug: Subcutaneous (SC) Abatacept; 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.; Other Names: Orencia; BMS-188667
Active Comparator: Intravenous (IV) Abatacept; 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).	Drug: Intravenous (IV) Abatacept; 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; Other Names: Orencia; BMS-188667

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169	The ACR 50 definition of improvement is a 50% improvement from baseline in the number of tender and swollen joint counts, and a 50% 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). ACR 70 is defined similarly with 70% improvements from baseline for tender and swollen joint counts and 3 out of 5 core measures.	Day 169
Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169	The disability section of the full HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. Higher scores=greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered.	Day 169
Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI	The HAQ-DI includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. HAQ-DI ranges from 0 to a maximum overall score of 3.0.	Baseline to Day 169
Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169	The disability section of the full HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3=unable to do. Higher scores=greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ-DI response=an improvement of at least 0.3 units from baseline in HAQ-DI.	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	AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug	Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.
Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died	AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.	Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.
Double-blind Period: Number of Participants With AEs of Special Interest	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs: all infections,serious infections,and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (prespecified AEs occurring within 1 hr of start of infusion), peri-infusional AEs (prespecified AEs occurring within 24 hrs of the start of infusion), system injection reactions, and local injection site reactions	Day 1 up to 56 days post last dose in short- term period or first dose in the long -term period, whichever occurs first.
Double-blind Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements	Vital sign measurements were performed for participants before and after infusion/subcutaneous injection of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.	Day 1 through end of short-term period (Day 169)
Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality	ULN=upper limit of normal; LLN=lower limit of normal; BL= baseline. Marked abnormality criteria: Hemoglobin: >3 g/dL decrease from BL; hematocrit: <0.75*BL; erythrocytes: <0.75*BL; platelets: <0.67*LLN/>1.5*ULN, or if BL<LLN, use <0.5*BL and <100,000 mm^3; leukocytes: <0.75*LLN/>1.25*ULN, or if BL<LLN use <0.8*BL or >ULN, or if BL>ULN, use >1.2*BL or <LLN; neutrophils+bands: <1.0*10^3 c/uL; eosinophils: >0.750*10^3 c/uL; basophils: >400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750*10^3 c/uL/>7.50*10^3 c/uL.	Day 1 through end of short-term period (Day 169)
Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality	Marked abnormality criteria: Alkaline phosphatase (ALP): >2*ULN, or if BL>ULN, use >3*BL; aspartate aminotransferase (AST): >3*ULN, or if BL>ULN, use >4*BL; alanine aminotransferase (ALT): >3*ULN, or if BL>ULN, use >4*BL; G-glutamyl transferase (GGT): >2* ULN, or if BL>ULN, use >3*BL; bilirubin: >2* ULN, or if BL>ULN, use >4*BL; blood urea nitrogen: >2* BL; creatinine: >1.5*BL	Day 1 through end of short-term period (Day 169)
Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality	Marked abnormality criteria: Sodium: <0.95*LLN/>1.05*ULN, or if BL<LLN, use <0.95* BL or >ULN, or if BL>ULN, use>1.05* BL or <LLN; potassium: <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN, use>1.1* BL or <LLN; chlorine: <0.9*LLN/>1.1* ULN, or if BL<LLN, use <0.9*BL or >ULN, or if BL>ULN, use>1.1*BL or <LLN; calcium: <0.8* LLN/>1.2* ULN, or if BL<LLN, use <0.75*BL or >ULN, or if BL>ULN, use>1.25* BL or <LLN; phosphorous: <0.75* LLN/>1.25*ULN, or if BL<LLN, use 0.67*BL or >ULN, or if BL>ULN, use>1.33* BL or <LLN	Day 1 through end of short-term period (Day 169)
Double-blind Period: Minimum Observed Serum Concentration of Abatacept		Days 57, 85, 113, 120, 127, 134, 141, and 169
Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept	Serum concentrations of abatacept were analyzed using a validated ELISA. Steady-state trough observed concentration in serum (Cminss) was measured in μg/mL. Samples were obtained on Days 57, 85, 113, 120, 127, 134, 141, and 169.	Days 57, 85, 113, 120, 127, 134, 141, and 169 (ST Period)
Double-blind Period: Maximum Observed Serum Concentration of Abatacept		End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous
Anti-TNF Failure Substudy Double Blind Period: Geometric Mean Maximum Observed Serum Concentration of Abatacept	Serum concentrations of abatacept were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Samples were obtained on Days 57, 85, 113, 120, 127, 134, 141, and 169. Cmax was measured in micrograms per milliliter (μg/mL).	End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous
Double-blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept		Dosing interval between Days 113 and 141 (TAU=28 days)
Anti-TNF Failure Sub-study Double Blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept	Serum concentrations of abatacept were analyzed using a validated ELISA. AUC(TAU) was measured as μg*h/mL. Samples for AUC (TAU) were obtained on Days 113, 120, 127, 134, and 141.	Dosing Interval between Days 113 and 141 (TAU=28 days)
Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA)	Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept (anti-ABA) or anti-CTLA4 antibody (anti-CTLA4).	Days 85, and 169 and postvisits on Days 28, 56, and 85
Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period	C-reactive protein is an acute phase reactant protein that is a clinical marker for rheumatoid arthritis. Time-matched median percent change from baseline= (time-matched baseline value - Post-baseline value)/time-matched baseline value*100, where the time-matched baseline value represents the median baseline value for only that cohort of participants with measurements available at that visit.	Baseline to Days 15, 29, 57, 85, 113, 141, and 169
Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized	An electrochemiluminescence immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; abatacept molecule). Ig and/or Junction (JNCT) category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a postbaseline titer higher than Baseline, or any postbaseline positivity if Baseline value was missing. Trt=treatment.	Days 85, and 169 and postvisits on Days 28, 56, and 85
Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline	Rheumatoid factor (RF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process.	Baseline to Day 169
Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821	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).	Days 169, 729, 1261, 1821
Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821	The ACR 50 definition of improvement is a 50% improvement from baseline in the number of tender and swollen joint counts, and a 50% 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). ACR 70 is defined similarly with 70% improvements from baseline for tender and swollen joint counts and 3 out of 5 core measures.	Days 169, 729, 1261, 1821
Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821	The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from "very good" to "very bad"). A higher DAS28 score indicates worse control of disease. High disease activity is > 5.1, low disease activity is < 3.2 and remission is < 2.6. A clinically significant response= decrease in DAS28 score of >1.2 from baseline.	Days 169, 729, 1261, 1821
Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821	The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from "very good" to "very bad"). A higher DAS28 score indicates worse control of disease. High disease activity is > 5.1, low disease activity is < 3.2 and remission is < 2.6.	Days 169, 729, 1261, 1821
Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821	The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from "very good" to "very bad"). A higher DAS28 score indicates worse control of disease. High disease activity is > 5.1, low disease activity is < 3.2 and remission is < 2.6.	Days 169, 729, 1261, 1821
Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821	The disability section of the full HAQ includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. HAQ-DI overall score ranges from a minimum of 0 to a maximum of 3.0. HAQ response was defined as an improvement (reduction) from baseline (Day 1) of at least 0.3 units in the HAQ score.	Days 169, 729, 1261, 1821
Open-Label LT 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	AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug	End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014)
Open-Label LT Period: Number of Participants With AEs of Special Interest	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs: all infections, serious infections, and opportunistic infections; autoimmune disorders; malignancies; system injection reactions, and local injection site reactions.	End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014)
Open-Label LT Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements	Vital sign assessments were performed in the LT period at 12-week intervals and at a yearly visit (at 16-week intervals) and, for participants who withdrew from the study prematurely, 7 days after the last dose of SC abatacept. Vital signs included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.	End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014)
Open-Label LT Period: Number of Participants With Clinically Significant Laboratory Abnormalities	Laboratory assessments were performed in the LT period at 12-week intervals and at a yearly visit and, for participants who withdrew from the study prematurely, 7 days after the last dose of SC abatacept. Abnormalities were determined to be clinically significant by the investigator.	End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• 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.
• Genovese 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.
• Genovese 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: November 15, 2007
• First Submitted That Met QC Criteria: November 15, 2007
• First Posted (Estimate): November 16, 2007

Study Record Updates

• Last Update Posted (Estimate): November 9, 2015
• Last Update Submitted That Met QC Criteria: November 5, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Immune Checkpoint Inhibitors; Abatacept
• Other Study ID Numbers: IM101-174; EUDRACT # 2007-005434-37