Methotrexate-Inadequate Response Study

Rheumatoid Arthritis (RA) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00559585
• Other study ID #: IM101-174
• Secondary ID: EUDRACT # 2007-0
• Status: Completed
• Phase: Phase 3
• First received: November 15, 2007
• Last updated: November 5, 2015
• Start date: January 2008
• Est. completion date: September 2014

Study information

• Verified date: November 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2492
• Est. completion date: September 2014
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis (RA)

Intervention

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.
• 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

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Ciudad Autonoma	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Rosario, Santa Fe	Santa Fe
Argentina	Local Institution	Santa Fe
Argentina	Local Institution	Tucuman
Australia	Local Institution	Cairns	Queensland
Australia	Local Institution	Heidelberg	Victoria
Australia	Local Institution	Maroochydore	Queensland
Australia	Local Institution	Shenton Park	Western Australia
Australia	Local Institution	St Leonards	New South Wales
Australia	Local Institution	Woodville	South Australia
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Hasselt
Belgium	Local Institution	Leuven
Belgium	Local Institution	Wilrijk
Belgium	Local Institution	Yvoir
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Juiz De Fora	Minas Gerais
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Recife	Pernambuco
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Mississauga	Ontario
Canada	Local Institution	Ottawa	Ontario
Canada	Local Institution	Saskatoon	Saskatchewan
Canada	Local Institution	St. John'S	Newfoundland and Labrador
Canada	Local Institution	Ste-Foy	Quebec
Canada	Local Institution	Ste-Foy	Quebec
Canada	Local Institution	Trois-Rivieres	Quebec
Canada	Local Institution	Winnipeg	Manitoba
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Santiago De Chile	Metropolitana
Chile	Local Institution	Santiago De Chile	Metropolitana
France	Local Institution	Bordeaux Cedex
France	Local Institution	Brest Cedex
France	Local Institution	Chambray Les Tours
France	Local Institution	Le Mans
France	Local Institution	Lille Cedex
France	Local Institution	Marseille
France	Local Institution	Nice Cedex 3
France	Local Institution	Paris Cedex 13
France	Local Institution	Paris Cedex 14
France	Local Institution	Poitiers
France	Local Institution	Strasbourg Cedex
Germany	Local Institution	Berlin
Germany	Local Institution	Leipzig
Germany	Local Institution	Muenchen
Germany	Local Institution	Munchen
Greece	Local Institution	Heraklion Crete
Hungary	Local Institution	Budapest
Hungary	Local Institution	Debrecen
India	Local Institution	Bangalore	Karnataka
India	Local Institution	Bangalore
India	Local Institution	Hyderabad
India	Local Institution	Lucknow
India	Local Institution	Navrangpura, Ahmedabad	Gujarat
India	Local Institution	New Delhi
India	Local Institution	Secunderabad	Andhra Pradesh
Ireland	Local Institution	Dublin
Italy	Local Institution	Napoli
Italy	Local Institution	Padova
Italy	Local Institution	Pavia
Italy	Local Institution	Roma
Italy	Local Institution	Siena
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Daejeon
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul	Sungdong-Gu
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Chihuahua
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	Mexico City	Distrito Federal
Mexico	Local Institution	Morelia	Michioacan
Mexico	Local Institution	Nuevo Leon
Mexico	Local Institution	Queretaro
Mexico	Local Institution	San Luis Potosi
Mexico	Local Institution	Tijuana	Baja California
Netherlands	Local Institution	Leeuwarden
Peru	Local Institution	Callao
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Poland	Local Institution	Bialystok
Poland	Local Institution	Bialystok
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Konskie
Poland	Local Institution	Krakow
Poland	Local Institution	Poznan
Poland	Local Institution	Poznan
Poland	Local Institution	Torun
Poland	Local Institution	Warszawa
Russian Federation	Local Institution	Ekaterinburg
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Yaroslavl
South Africa	Local Institution	Durban	Kwa Zulu Natal
South Africa	Local Institution	Kempton Park	Gauteng
South Africa	Local Institution	Muckleneuk	Gauteng
South Africa	Local Institution	Muckleneuk	Gauteng
South Africa	Local Institution	Panorama	Western Cape
South Africa	Local Institution	Pretoria	Gauteng
Taiwan	Local Institution	Kaohsiung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taichung
Taiwan	Local Institution	Taichung
Turkey	Local Institution	Denizli
Turkey	Local Institution	Edirne
Turkey	Local Institution	Gaziantep
United Kingdom	Local Institution	Bridgend	Glamorgan
United Kingdom	Local Institution	Cambridge	Cambridgeshire
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	Local Institution	Southampton	Hampshire
United States	The Center For Rheumatology, Llp	Albany	New York
United States	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico
United States	Albuquerque Rehabilitation & Rheumatology Pc	Albuquerque	New Mexico
United States	Arthritis Clinic Of Northern Virginia, P.C.	Arlington	Virginia
United States	Asheville Rheumatology & Osteoporosis Research Asso P. A.	Asheville	North Carolina
United States	Arthritis & Rheumatology Of Georgia,Pc	Atlanta	Georgia
United States	Walter F. Chase	Austin	Texas
United States	Arthritis And Rheumatic Disease Specialties	Aventura	Florida
United States	East Penn Rheumatology Associates	Bethlehem	Pennsylvania
United States	Rheumatology Associates, Pc	Birmingham	Alabama
United States	Boise Rheumatology/ Intermountain Research Center, Inc	Boise	Idaho
United States	Boulder Medical Center	Boulder	Colorado
United States	Guadagnoli, Germano	Bridgeport	Connecticut
United States	Joao Nascimento	Bridgeport	Connecticut
United States	Low Country Rheumatology, Pa	Charleston	South Carolina
United States	The Arthritis Clinic & Carolina Bone & Joint	Charlotte	North Carolina
United States	Center For Arthritis & Rheumatic Diseases, Pc	Chesapeake	Virginia
United States	Cincinnati Rheumatic Disease Study Group	Cincinnati	Ohio
United States	Coeur D'Alene Arthrit Clin	Coeur D Alene	Idaho
United States	Arthritis Assoc And Osteo Ctr Of Col Sprgs	Colorado Springs	Colorado
United States	Columbia Arthritis Center	Columbia	South Carolina
United States	Klein And Associates, M.D., Pa	Cumberland	Maryland
United States	Clinical Research Center Of Ct/Ny	Danbury	Connecticut
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Allergy And Arthritis Associates	Dover	New Jersey
United States	Rheumatology	Durham	North Carolina
United States	Pro Research	Eugene	Oregon
United States	Physicians East, Pa	Greenville	North Carolina
United States	St. Joseph'S Mercy Clinic	Hot Springs	Arkansas
United States	Accurate Clinical Research	Houston	Texas
United States	Rheumatic Disease Clinical Research Center, Llc	Houston	Texas
United States	Talbert Medical Group	Huntington Beach	California
United States	Arthritis Assoicates Of Mississippi	Jackson	Mississippi
United States	Arthritis Clinic	Jackson	Tennessee
United States	Rheumatology Consultants Pllc	Knoxville	Tennessee
United States	Allergy & Rheumatology Medical Clinic, Inc.	La Jolla	California
United States	Portland Rheumatology Clinic, Llc	Lake Oswego	Oregon
United States	Kansas City Internal Medicine	Lee'S Summit	Missouri
United States	Physician Research Collaboration, Llc	Lincoln	Nebraska
United States	Valerius Medical Group &Research Ctr. Of Greater Long Beach	Long Beach	California
United States	Arthritis Center Of The Rockies, Pc	Loveland	Colorado
United States	The Arthritis Group, Pc	Memphis	Tennessee
United States	Coastal Clinical Research, Inc	Mobile	Alabama
United States	Carolina Health Specialists	Myrtle Beach	South Carolina
United States	St. Thomas Hospital Tower East	Nashville	Tennessee
United States	Health Research Of Oklahoma	Oklahoma City	Oklahoma
United States	Southern Tier Arthritis & Rheumatism	Olean	New York
United States	South Puget Sound Clinincal Research Center	Olympia	Washington
United States	Arthritis & Osteoporosis Treatment Center, Pa	Orange Park	Florida
United States	Acme Research, Llc	Orangeburg	South Carolina
United States	Rheumatology Associates Of Central Florida	Orlando	Florida
United States	The Arthritis Center	Palm Harbor	Florida
United States	Stanford University School Of Medicine	Palo Alto	California
United States	Rheumatology Associates	Providence	Rhode Island
United States	Quincy Medical Group	Quincy	Illinois
United States	Rockford Orthopedic Associates, Ltd.	Rockford	Illinois
United States	San Diego Arthritis Medical Clinic	San Diego	California
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	Advanced Arthritis Care & Research	Scottsdale	Arizona
United States	The Arthritis Center	Springfield	Illinois
United States	Shores Rheumatology, P. C.	St. Clair Shores	Michigan
United States	Carolina Pharmaceutical Research	Statesville	North Carolina
United States	Texas Research Center	Sugarland	Texas
United States	Arthritis Health Associates	Syracuse	New York
United States	Tacoma Center For Arthritis Research Ps	Tacoma	Washington
United States	Catalina Pointe Clinical Research, Inc.	Tucson	Arizona
United States	Healthcare Research Consultants	Tulsa	Oklahoma
United States	Oklahoma Center For Arthritis Therapy And Research	Tulsa	Oklahoma
United States	Carolina Arthritis Associates	Wilmington	North Carolina
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  France,  Germany,  Greece,  Hungary,  India,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Poland,  Russian Federation,  South Africa,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	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.	Yes
Secondary	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)	Yes
Secondary	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	Day 1 through end of short-term period (Day 169)	Yes
Secondary	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)	Yes
Secondary	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	Day 1 through end of short-term period (Day 169)	Yes
Secondary	Double-blind Period: Minimum Observed Serum Concentration of Abatacept		Days 57, 85, 113, 120, 127, 134, 141, and 169	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form