A Study of Abatacept in Patients With Active Ulcerative Colitis

Ulcerative Colitis Clinical Trial

Official title:

A Phase 3, Multi-Center, Randomized, Placebo-Controlled Study to Evaluate the Clinical Efficacy and Safety of Induction and Maintenance Therapy With Abatacept in Subjects With Active Ulcerative Colitis (UC) Who Have Had an Inadequate Clinical Response and/or Intolerance to Medical Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00410410
• Other study ID #: IM101-108
• Status: Completed
• Phase: Phase 3
• First received: December 11, 2006
• Last updated: March 4, 2015
• Start date: December 2006
• Est. completion date: November 2009

Study information

• Verified date: March 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 clinical research study is to learn if abatacept can improve signs and symptoms of active ulcerative colitis in patients who have not had an adequate response to other therapies. The safety of this treatment will also be studied

Description:

The Induction Period First Cohort (IP1C) arms (30/10 mg/kg and 10 mg/kg) were placebo-controlled arms that were used for the primary endpoint and its analysis. The Induction Period Second Cohort arms (IP2C 30/10 mg/kg and 10 mg/kg) were not placebo-controlled, their sole purpose being to provide sufficient numbers of participants for the maintenance phase. The first cohort (IP1C) was randomized to receive placebo or 1 of 3 doses of abatacept. Following completion of the IP1C randomization, a second cohort (IP2C) was randomized to receive 1 of 2 doses of abatacept. After all participants in the IP1C completed or discontinued, the data was locked and the formal analysis for the Induction Period primary endpoint was performed. Summary tables for the second cohort (IP2C) and the Maintenance and Open-label phases were generated from a second, subsequent data lock.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 591
• Est. completion date: November 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men or women 18 years or older

• Ulcerative colitis for at lease 3 months

• Moderate to severe active ulcerative colitis

• Inadequate response or intolerance to standard ulcerative colitis treatment

Study Design

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• abatacept (ABA)
Dextrose 5% in water, IV. Placebo on days IP-1, IP-15,IP-29, IP-57; 3 mg/kg on days IP-1, IP-15,IP-29, IP-57; 10 mg/kg on days IP-1, IP-15,IP-29, IP-57; or 30 mg/kg on days IP-1,IP-15 and ~10 mg/kg on days IP-29, IP-57 (ABA 30/~10 mg/kg Group). Induction Period 3 months Maintenance Period 12 months
• placebo
Normal saline, IV, 0 mg/kg, every 28 days. Induction Period 3 months Maintenance Period 12 months
• abatacept
~10 mg/kg, once monthly Open- Label Extension Period until the drug is marketed for UC or the UC development program for abatacept is discontinued

Locations

Country	Name	City	State
Australia	Local Institution	Bedford Park	South Australia
Australia	Local Institution	Box Hill	Victoria
Australia	Local Institution	Camperdown	New South Wales
Australia	Local Institution	Fitzroy	Victoria
Australia	Local Institution	Fremantle	Western Australia
Australia	Local Institution	Garran	Australian Capital Territory
Australia	Local Institution	Herston	Queensland
Australia	Local Institution	Launceston	Tasmania
Australia	Local Institution	South Ballarat	Victoria
Australia	Local Institution	South Brisbane	Queensland
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Leuven
Brazil	Local Institution	Campinas	Sao Paulo
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Goiania	Goias
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Rio De Janeiro
Brazil	Local Institution	Salvador	Bahia
Brazil	Local Institution	Santo Andre - Sp	Sao Paulo
Brazil	Local Institution	Santos	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Kingston	Ontario
Canada	Local Institution	Levis	Quebec
Canada	Local Institution	London	Ontario
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Ottawa	Ontario
Canada	Local Institution	Quebec
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Vancouver	British Columbia
Canada	Local Institution	Vancouver	British Columbia
Czech Republic	Local Institution	Brno - Bohunice
Czech Republic	Local Institution	Ceske Budejovice
France	Local Institution	Amiens Cedex 1
France	Local Institution	Clichy
France	Local Institution	Lille Cedex
France	Local Institution	Nice
France	Local Institution	Paris
France	Local Institution	Pessac
France	Local Institution	Toulouse
Germany	Local Institution	Kiel
Germany	Local Institution	Muenster
Germany	Local Institution	Muenster
India	Local Institution	Bangalore
India	Local Institution	Bangalore
India	Local Institution	Delhi
India	Local Institution	Hyderabad
India	Local Institution	Hyderabad	Andhra Pradesh
India	Local Institution	Kochi	Kerala
India	Local Institution	Mangalore
India	Local Institution	Manipal
India	Local Institution	Mumbai
India	Local Institution	Mumbai
India	Local Institution	Mumbai	Maharashtra
India	Local Institution	Mysore
Ireland	Local Institution	Dublin
Ireland	Local Institution	Dublin 9	Dublin
Italy	Local Institution	Napoli
Italy	Local Institution	Padova
Italy	Local Institution	Roma
Italy	Local Institution	Roma
Italy	Local Institution	San Giovanni Rotondo
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	Chihuahua
Mexico	Local Institution	Culiacan	Sinaloa
Mexico	Local Institution	Df	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Hermosillo	Sonora
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Mexico, D. F.	Distrito Federal
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Torreon	Coahuila
Netherlands	Local Institution	Amersfoort
Netherlands	Local Institution	Amsterdam
Netherlands	Local Institution	Groningen
Poland	Local Institution	Katowice
Poland	Local Institution	Warszawa
Poland	Local Institution	Wroclaw
Puerto Rico	Local Institution	Ponce
South Africa	Local Institution	Belville	Western Cape
South Africa	Local Institution	Overport	Kwa Zulu Natal
South Africa	Local Institution	Panorama	Western Cape
South Africa	Local Institution	Parktown West	Gauteng
South Africa	Local Institution	Pretoria	Gauteng
Switzerland	Local Institution	Bern
Switzerland	Local Institution	Zuerich
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	London	Greater London
United Kingdom	Local Institution	Oxford	Oxfordshire
United States	Atlanta Gastroenterology Associates	Atlanta	Georgia
United States	Austin Gastroenterology, Pa	Austin	Texas
United States	University Of Alabama At Birmingham	Birmingham	Alabama
United States	Gastroenterology Specialists, Inc.	Canton	Ohio
United States	University Of North Carolina	Chapel Hill	North Carolina
United States	Medical University Of South Carolina	Charleston	South Carolina
United States	Charlotte Gastroenterology & Hepatology, Pllc	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University Of Chicago Hospitals	Chicago	Illinois
United States	Consultants For Clinical Research, Inc.	Cincinnati	Ohio
United States	Gastrointestinal & Liver Diseases Consultants	Dayton	Ohio
United States	Aga Clinical Research Associates, Llc	Egg Harbor Twp	New Jersey
United States	Hudson Valley Medical Research Llc	Fishkill	New York
United States	University Of Florida	Gainesville	Florida
United States	Gastroenterology Center Of The Midsouth, P.C.	Germantown	Tennessee
United States	Memphis Gastroenterology Group	Germantown	Tennessee
United States	Long Island Clinical Research	Great Neck	New York
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	Kansas City Gastroenterology And Hepatology	Kansas City	Missouri
United States	Gulf Coast Research	Lafayette	Louisiana
United States	University Of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University Of Louisville	Louisville	Kentucky
United States	Center For Digestive & Liver Diseases, Inc.	Mexico	Missouri
United States	Miami Research Associates	Miami	Florida
United States	Nashville Medical Research	Nashville	Tennessee
United States	Mount Sinai School Of Medicine	New York	New York
United States	Oklahoma Foundation For Digestive Research	Oklahoma City	Oklahoma
United States	Hospital Of The University Of Pennsylvania	Philadelphia	Pennsylvania
United States	Allegheny Center For Digestive Health	Pittsburgh	Pennsylvania
United States	Minnesota Gastroenterology, P.A.	Plymouth	Minnesota
United States	Health Science Center	Pratt	Kansas
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University Of Rochester Medical Center	Rochester	New York
United States	Good, Larry I.	Rockville Centre	New York
United States	The Permanente Medical Group, Inc	Sacramento	California
United States	Alamo Medical Research	San Antonio	Texas
United States	Gastroenterology Clinic Of San Antonio	San Antonio	Texas
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Gastrointestinal Resrch Assoc.	Setauket	New York
United States	Tacoma Digestive Disease Research Ctr.	Tacoma	Washington
United States	Litchfield County Gastroenterology Assoc.	Torrington	Connecticut
United States	Healthcare Research Consultants	Tulsa	Oklahoma
United States	Options Health Research, Llc	Tulsa	Oklahoma
United States	Western States Clinical Research Inc.	Wheatridge	Colorado
United States	Hanover Medical Specialists, P.A.	Wilmington	North Carolina
United States	Piedmont Medical Research Associates	Winston Salem	North Carolina
United States	Shafran Gasteroenterology Center	Winter Park	Florida
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Czech Republic,  France,  Germany,  India,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Puerto Rico,  South Africa,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Induction Period (IP); Number of Participants With Clinical Response (Per Mayo Score) at Week 12: IP Cohort 1 (IP1C)	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of = 3 points and = 30%, with an accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point.	Week 12 (Day IP-85)	No
Primary	Maintenance Period (MP); Number of Participants With Clinical Response (Per Mayo Score) at Month 12	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of = 3 points and = 30%, with an accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point.	Month 12 (Day MP-365)	No
Primary	Open-Label Extension Period (OL); Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. 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 OL-1 through the end of the OL	Yes
Primary	OL; Number of Participants With AEs of Special Interest	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which 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, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).	Day OL-1 through Day OL-729	Yes
Primary	OL; Number of Participants With Physical Examination Findings	Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).	Day OL-1 through Day OL-729	Yes
Primary	OL; Number of Participants With Marked Hematology Laboratory Abnormalities	High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL.	Day OL-1 through Day OL-729	Yes
Primary	OL; Number of Participants With Liver and Kidney Function and Electrolyte Laboratory Abnormalities	Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; potassium (K): <0.9 x LLN/ >1.1 x ULN; calcium (Ca): <0.8 x LLN/>1.2 x ULN; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN	Day OL-1 through Day OL-729	Yes
Primary	OL; Number of Participants With Chemistry and Urinalysis Laboratory Abnormalities	Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; fasting serum Glu: <0.8 x LLN/ >1.5 x ULN; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN; uric acid: >1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use =2 when BL value missing or value =4, or when pre-dose=0 or 0.5. Use =3 when pre-dose=1. Use =4 when pre-dose=2 or 3	Day OL-1 through Day OL-729	Yes
Secondary	IP; Baseline Mayo Score: IP1C	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of = 3 points and = 30%, with an accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point.	Baseline	Yes
Secondary	IP; Number of Participants in Clinical Remission (Per Mayo Score) at Week 12: IP1C	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of = 2 points with no individual subscore exceeding 1 point.	Week 12 (Day IP-85)	No
Secondary	IP; Number of Participants in Mucosal Healing (Per Mayo Score) at Week 12: IP1C	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore = 1 point	Week 12 (Day IP-85)	No
Secondary	IP; Number of Participants With Clinical Response (Per Mayo Score) at Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of = 3 points and = 30%, with an accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point.	Week 12 (Day IP-85)	No
Secondary	IP; Baseline Inflammatory Bowel Disease Questionnaire (IBDQ) Score: IP1C	The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.	Baseline	Yes
Secondary	IP; Mean Change From Baseline To Week 12 in Inflammatory Bowel Disease Questionnaire (IBDQ): IP1C	The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.	Baseline (Day IP-1), Day IP-85 (Week 12)	No
Secondary	IP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (=1 Point) at Week 12: IP1C	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute rectal bleeding subscore of =1 point was indicative of mild disease.	Day IP-85 (Week 12)	No
Secondary	IP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (=1 Point) at Week 12: IP1C	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute stool frequency subscore of =1 point was indicative of mild disease.	Day IP-85 (Week 12)	No
Secondary	IP; Number of Participants With Mayo Physician Global Assessment (PGA) Subscores Indicating Mild Disease (=1 Point) at Week 12: IP1C	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute PGA subscore of =1 point was indicative of mild disease.	Day IP-85 (Week 12)	No
Secondary	IP; Number of Participants Who Are Anti-TNF-Inadequate Responders/Anti-TNF Intolerant With Clinical Response At Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C	The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of = 3 points and = 30%, with accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for =8 weeks.	Week 12 (Day IP-85)	No
Secondary	IP; Number of Participants With Clinical Response At Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C	The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of = 3 points and = 30%, with accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for =8 weeks.	Week 12 (Day IP-85)	No
Secondary	IP; Number of Participants in Clinical Remission at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C	The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical remission is defined as a Mayo score of = 2 points with no individual subscore exceeding 1 point. Inadequate response/intolerance; =inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for =8 weeks.	Week 12 (Day IP-85)	No
Secondary	IP; Number of Participants in Mucosal Healing at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore = 1 point. Inadequate response/intolerance = inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for =8 weeks.	Week 12 (Day IP-85)	No
Secondary	IP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation: IP1C + IP2C	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. 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 IP-1 through Day IP-85	Yes
Secondary	IP; Number of Participants With AEs Of Special Interest: IP1C + IP2C	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which 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, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).	Day IP-1 through Day IP-85	Yes
Secondary	IP; Number of Participants With Physical Examination Findings: IP1C + IP2C	Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).	Day IP-1 through Day IP-85	Yes
Secondary	IP; Number of Participants With Marked Hematology Laboratory Abnormalities: IP1C	High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL.	Day IP-1 through Day IP-85	Yes
Secondary	IP; Number of Participants With Marked Liver and Kidney Function and Electrolyte Laboratory Abnormalities: IP1C	Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; Sodium (Na): <0.95 x LLN/ >1.05 x ULN; potassium (K): <0.9 x LLN/ >1.1 x ULN; calcium (Ca): <0.8 x LLN/>1.2 x ULN; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN	Day IP-1 through Day IP-85	Yes
Secondary	IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP1C	Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN; uric acid: >1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use =2 when BL value missing or value =4, or when pre-dose=0 or 0.5. Use =3 when pre-dose=1. Use =4 when pre-dose=2 or 3	Day IP-1 through Day IP-85	Yes
Secondary	IP; Number of Participants With Marked Hematology, Liver and Kidney Function, and Electrolyte Laboratory Abnormalities: IP2C	High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; Sodium (Na): <0.95 x LLN/ >1.05 x ULN; potassium (K): <0.9 x LLN/ >1.1 x ULN; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN;	Day IP-1 through Day IP-85	Yes
Secondary	IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP2C	Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use =2 when BL value missing or value =4, or when pre-dose=0 or 0.5. Use =3 when pre-dose=1. Use =4 when pre-dose=2 or 3	Day IP-1 through Day IP-85	Yes
Secondary	IP; Number of Participants With Abatacept-Induced Antibodies: IP1C + IP2C	A electrochemiluminescent 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 category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.	For participants treated in MP: Day IP-1 (Baseline) to Day MP-1 (Day IP-85). For participants treated in OL directly after IP: Day IP-1 to Day OL-1. For participants treated only in IP: All measurements after Day IP-1 (including follow-up visits)	No
Secondary	MP; Number of Participants in Clinical Remission at Month 12	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of = 2 points with no individual subscore exceeding 1 point.	Month 12 (Day MP-365)	No
Secondary	MP; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (=1 Point) at Month 12	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore = 1 point	Month 12 (Day MP-365)	No
Secondary	MP; Number of Participants in Clinical Remission at Both Month 6 and Month 12	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of = 2 points with no individual subscore exceeding 1 point.	Month 6 (Day MP-169), Month 12 (Day MP-365)	No
Secondary	MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids and Achieved Clinical Remission by Month 12	Baseline corticosteroids equivalent of =30 mg prednisone daily. The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater frequency or severity. Clinical remission is defined as a Mayo score of = 2 points with no individual subscore exceeding 1 point.	Day MP-365 (Month 12)	No
Secondary	MP; Mean Change From Baseline to Month 12 in IBDQ	The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.	Day MP-365	No
Secondary	MP; Mean Change From Baseline to Month 12 in Short Form-36 (SF-36)	The SF-36 is a validated instrument to measure health-related quality of life across multiple disease states. Individual subscale scores and 2 summary scores are calculated: (1) physical component summary (PCS) which includes physical functioning, role-physical, bodily pain, and general health; (2) mental component summary (MCS) which includes vitality, social functioning, role-emotional, and mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight, with values ranging from worse health (0) to best health (100).	Day MP-365	No
Secondary	MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids for 90 Consecutive Days and Achieved Clinical Remission by Month 12	Baseline corticosteroids equivalent of =30 mg prednisone daily. The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater frequency or severity. Clinical remission is defined as a Mayo score of = 2 points with no individual subscore exceeding 1 point.	Day MP-365 (Month 12)	No
Secondary	MP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (=1 Point) at Month 12	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute rectal bleeding subscore of =1 point was indicative of mild disease.	Day MP-365 (Month 12)	No
Secondary	MP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (=1 Point) at Month 12	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute stool frequency subscore of =1 point was indicative of mild disease.	Day MP-365 (Month 12)	No
Secondary	MP; Number of Participants With Mayo PGA Subscores Indicating Mild Disease (=1 Point) at Month 12	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute PGA subscore of =1 point was indicative of mild disease.	Day MP-365 (Month 12)	No
Secondary	MP; Number of Participants With Clinical Response at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)	The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of = 3 points and = 30%, with accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for =8 weeks.	Month 12 (Day MP-365)	No
Secondary	MP; Number of Participants With Clinical Remission at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)	The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical remission is defined as a Mayo score of = 2 points with no individual subscore exceeding 1 point. Inadequate response/intolerance =inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for =8 weeks.	Month 12 (Day MP-365)	No
Secondary	MP; Number of Participants With Clinical Mucosal Healing at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore =1 point. Inadequate response/intolerance = inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for =8 weeks.	Month 12 (Day MP-365)	No
Secondary	MP; Number of Participants With Abatacept-Induced Antibodies	A electrochemiluminescent 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 category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.	For participants not entering OL: All measurements starting after Day MP-1 (including follow-up visits). For participants entering OL: From first measurement after Day MP-1 to Day MP-365 (Day OL-1).	No
Secondary	MP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. 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 MP-1 through Day MP-365	Yes
Secondary	MP; Number of Participants With AEs of Special Interest	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which 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, including all infections, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).	Day MP-1 through Day MP-365	Yes
Secondary	MP; Number of Participants With Physical Examination Findings	Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).	Day IP-85 through Day MP-365	Yes
Secondary	MP; Number of Participants With Marked Hematology Laboratory Abnormalities	High=greater than ULN, Low=lower than LLN. LLN/ULN= HGB: >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; PLT: <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; GGT: >2 x ULN; Bilirubin: >2 x ULN; BUN: >2 x BL; Na: <0.95 x LLN/ >1.05 x ULN; K: <0.9 x LLN/ >1.1 x ULN; Ca: <0.8 x LLN/>1.2 x ULN	Day IP-85 through Day MP-365	Yes
Secondary	MP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities	Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; fasting serum Glu: <0.8 x LLN/ >1.5 x ULN; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN; uric acid: >1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use =2 when BL value missing or value =4, or when pre-dose=0 or 0.5. Use =3 when pre-dose=1. Use =4 when pre-dose=2 or 3	Day IP-85 through Day MP-365	Yes
Secondary	OL; Number of Participants With Clinical Response Over Time	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of = 3 points and = 30%, with an accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point.	Day OL-1 through Day OL-729	No
Secondary	OL; Number of Participants With Clinical Remission Over Time	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of = 2 points with no individual subscore exceeding 1 point.	Day OL-1 through Day OL-729	No
Secondary	OL; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (=1 Point) During OL	The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore = 1 point	Open-Label Period (Day OL-1 through Day OL-729)	No
Secondary	OL; Number of Participants With Clinical Response or Clinical Remission Upon Retreatment With Abatacept Among Those Who Received Abatacept in the IP or MP Period	The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of = 3 points and = 30%, with accompanying decrease in the rectal bleeding subscore of = 1 point or absolute rectal bleeding subscore of = 1 point. Clinical remission = Mayo score of = 2 points with no individual subscore exceeding 1 point. Change from Baseline= post-Baseline - Baseline value.	Last Study Visit (Day OL-729)	No
Secondary	OL; Number of Participants With Abatacept-Induced Antibodies	A electrochemiluminescent 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 category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.	For participants receiving OL medication, all measurements starting after Day OL-1 (including follow-up visits and at 56 and 85 days after last dose)	No
Secondary	OL; Number of Participants Using Corticosteroids During OL	Participants taking oral corticosteroids (equivalent of = 30 mg prednisone daily) must have met minimum treatment duration at entry into IP and had stable dose for =2 weeks prior to entry into the IP.	Day OL-1 through Day OL-729	No

External Links

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