Clinical trial NCT00410410: A Study of Abatacept in Patients With Active Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-12-12
Enrollment: 591
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Induction Period (IP); Number of Participants With Clinical Response (Per Mayo Score) at Week 12: IP Cohort 1 (IP1C)
timeFrame: Week 12 (Day IP-85)
measure: Maintenance Period (MP); Number of Participants With Clinical Response (Per Mayo Score) at Month 12
timeFrame: Month 12 (Day MP-365)
measure: 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
timeFrame: Day OL-1 through the end of the OL
measure: OL; Number of Participants With AEs of Special Interest
timeFrame: Day OL-1 through Day OL-729
measure: OL; Number of Participants With Physical Examination Findings
timeFrame: Day OL-1 through Day OL-729
measure: OL; Number of Participants With Marked Hematology Laboratory Abnormalities
timeFrame: Day OL-1 through Day OL-729
measure: OL; Number of Participants With Liver and Kidney Function and Electrolyte Laboratory Abnormalities
timeFrame: Day OL-1 through Day OL-729
measure: OL; Number of Participants With Chemistry and Urinalysis Laboratory Abnormalities
timeFrame: Day OL-1 through Day OL-729
Secondary outcomes:
measure: IP; Baseline Mayo Score: IP1C
timeFrame: Baseline
measure: IP; Number of Participants in Clinical Remission (Per Mayo Score) at Week 12: IP1C
timeFrame: Week 12 (Day IP-85)
measure: IP; Number of Participants in Mucosal Healing (Per Mayo Score) at Week 12: IP1C
timeFrame: Week 12 (Day IP-85)
measure: IP; Number of Participants With Clinical Response (Per Mayo Score) at Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C
timeFrame: Week 12 (Day IP-85)
measure: IP; Baseline Inflammatory Bowel Disease Questionnaire (IBDQ) Score: IP1C
timeFrame: Baseline
measure: IP; Mean Change From Baseline To Week 12 in Inflammatory Bowel Disease Questionnaire (IBDQ): IP1C
timeFrame: Baseline (Day IP-1), Day IP-85 (Week 12)
measure: IP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C
timeFrame: Day IP-85 (Week 12)
measure: IP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C
timeFrame: Day IP-85 (Week 12)
measure: IP; Number of Participants With Mayo Physician Global Assessment (PGA) Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C
timeFrame: Day IP-85 (Week 12)
measure: 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
timeFrame: Week 12 (Day IP-85)
measure: IP; Number of Participants With Clinical Response At Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C
timeFrame: Week 12 (Day IP-85)
measure: IP; Number of Participants in Clinical Remission at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C
timeFrame: Week 12 (Day IP-85)
measure: IP; Number of Participants in Mucosal Healing at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C
timeFrame: Week 12 (Day IP-85)
measure: IP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation: IP1C + IP2C
timeFrame: Day IP-1 through Day IP-85
measure: IP; Number of Participants With AEs Of Special Interest: IP1C + IP2C
timeFrame: Day IP-1 through Day IP-85
measure: IP; Number of Participants With Physical Examination Findings: IP1C + IP2C
timeFrame: Day IP-1 through Day IP-85
measure: IP; Number of Participants With Marked Hematology Laboratory Abnormalities: IP1C
timeFrame: Day IP-1 through Day IP-85
measure: IP; Number of Participants With Marked Liver and Kidney Function and Electrolyte Laboratory Abnormalities: IP1C
timeFrame: Day IP-1 through Day IP-85
measure: IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP1C
timeFrame: Day IP-1 through Day IP-85
measure: IP; Number of Participants With Marked Hematology, Liver and Kidney Function, and Electrolyte Laboratory Abnormalities: IP2C
timeFrame: Day IP-1 through Day IP-85
measure: IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP2C
timeFrame: Day IP-1 through Day IP-85
measure: IP; Number of Participants With Abatacept-Induced Antibodies: IP1C + IP2C
timeFrame: 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)
measure: MP; Number of Participants in Clinical Remission at Month 12
timeFrame: Month 12 (Day MP-365)
measure: MP; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (≤1 Point) at Month 12
timeFrame: Month 12 (Day MP-365)
measure: MP; Number of Participants in Clinical Remission at Both Month 6 and Month 12
timeFrame: Month 6 (Day MP-169), Month 12 (Day MP-365)
measure: MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids and Achieved Clinical Remission by Month 12
timeFrame: Day MP-365 (Month 12)
measure: MP; Mean Change From Baseline to Month 12 in IBDQ
timeFrame: Day MP-365
measure: MP; Mean Change From Baseline to Month 12 in Short Form-36 (SF-36)
timeFrame: Day MP-365
measure: MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids for 90 Consecutive Days and Achieved Clinical Remission by Month 12
timeFrame: Day MP-365 (Month 12)
measure: MP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Month 12
timeFrame: Day MP-365 (Month 12)
measure: MP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Month 12
timeFrame: Day MP-365 (Month 12)
measure: MP; Number of Participants With Mayo PGA Subscores Indicating Mild Disease (≤1 Point) at Month 12
timeFrame: Day MP-365 (Month 12)
measure: MP; Number of Participants With Clinical Response at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)
timeFrame: Month 12 (Day MP-365)
measure: MP; Number of Participants With Clinical Remission at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)
timeFrame: Month 12 (Day MP-365)
measure: MP; Number of Participants With Clinical Mucosal Healing at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)
timeFrame: Month 12 (Day MP-365)
measure: MP; Number of Participants With Abatacept-Induced Antibodies
timeFrame: 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).
measure: MP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation
timeFrame: Day MP-1 through Day MP-365
measure: MP; Number of Participants With AEs of Special Interest
timeFrame: Day MP-1 through Day MP-365
measure: MP; Number of Participants With Physical Examination Findings
timeFrame: Day IP-85 through Day MP-365
measure: MP; Number of Participants With Marked Hematology Laboratory Abnormalities
timeFrame: Day IP-85 through Day MP-365
measure: MP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities
timeFrame: Day IP-85 through Day MP-365
measure: OL; Number of Participants With Clinical Response Over Time
timeFrame: Day OL-1 through Day OL-729
measure: OL; Number of Participants With Clinical Remission Over Time
timeFrame: Day OL-1 through Day OL-729
measure: OL; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (≤1 Point) During OL
timeFrame: Open-Label Period (Day OL-1 through Day OL-729)
measure: 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
timeFrame: Last Study Visit (Day OL-729)
measure: OL; Number of Participants With Abatacept-Induced Antibodies
timeFrame: 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)
measure: OL; Number of Participants Using Corticosteroids During OL
timeFrame: Day OL-1 through Day OL-729
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: The Permanente Medical Group, Inc
state: California
city: Wheatridge
country: United States
facility: Western States Clinical Research Inc.
state: Colorado
city: Torrington
country: United States
facility: Litchfield County Gastroenterology Assoc.
state: Connecticut
city: Gainesville
country: United States
facility: University Of Florida
state: Florida
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Winter Park
country: United States
facility: Shafran Gasteroenterology Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University Of Chicago Hospitals
state: Illinois
city: Pratt
country: United States
facility: Health Science Center
state: Kansas
city: Lexington
country: United States
facility: University Of Kentucky Chandler Medical Center
state: Kentucky
city: Louisville
country: United States
facility: University Of Louisville
state: Kentucky
city: Lafayette
country: United States
facility: Gulf Coast Research
state: Louisiana
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Plymouth
country: United States
facility: Minnesota Gastroenterology, P.A.
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Kansas City Gastroenterology And Hepatology
state: Missouri
city: Mexico
country: United States
facility: Center For Digestive & Liver Diseases, Inc.
state: Missouri
city: Egg Harbor Twp
country: United States
facility: Aga Clinical Research Associates, Llc
state: New Jersey
city: Fishkill
country: United States
facility: Hudson Valley Medical Research Llc
state: New York
city: Great Neck
country: United States
facility: Long Island Clinical Research
state: New York
city: New York
country: United States
facility: Mount Sinai School Of Medicine
state: New York
city: Rochester
country: United States
facility: University Of Rochester Medical Center
state: New York
city: Rockville Centre
country: United States
facility: Good, Larry I.
state: New York
city: Setauket
country: United States
facility: Gastrointestinal Resrch Assoc.
state: New York
city: Chapel Hill
country: United States
facility: University Of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Gastroenterology & Hepatology, Pllc
state: North Carolina
city: Wilmington
country: United States
facility: Hanover Medical Specialists, P.A.
state: North Carolina
city: Winston Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: Canton
country: United States
facility: Gastroenterology Specialists, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Consultants For Clinical Research, Inc.
state: Ohio
city: Dayton
country: United States
facility: Gastrointestinal & Liver Diseases Consultants
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Foundation For Digestive Research
state: Oklahoma
city: Tulsa
country: United States
facility: Options Health Research, Llc
state: Oklahoma
city: Tulsa
country: United States
facility: Healthcare Research Consultants
state: Oklahoma
city: Philadelphia
country: United States
facility: Hospital Of The University Of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Center For Digestive Health
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University Of South Carolina
state: South Carolina
city: Germantown
country: United States
facility: Gastroenterology Center Of The Midsouth, P.C.
state: Tennessee
city: Germantown
country: United States
facility: Memphis Gastroenterology Group
state: Tennessee
city: Nashville
country: United States
facility: Nashville Medical Research
state: Tennessee
city: Austin
country: United States
facility: Austin Gastroenterology, Pa
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: San Antonio
country: United States
facility: Gastroenterology Clinic Of San Antonio
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Tacoma
country: United States
facility: Tacoma Digestive Disease Research Ctr.
state: Washington
city: Garran
country: Australia
facility: Local Institution
state: Australian Capital Territory
city: Camperdown
country: Australia
facility: Local Institution
state: New South Wales
city: Herston
country: Australia
facility: Local Institution
state: Queensland
city: South Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: Bedford Park
country: Australia
facility: Local Institution
state: South Australia
city: Launceston
country: Australia
facility: Local Institution
state: Tasmania
city: Box Hill
country: Australia
facility: Local Institution
state: Victoria
city: Fitzroy
country: Australia
facility: Local Institution
state: Victoria
city: South Ballarat
country: Australia
facility: Local Institution
state: Victoria
city: Fremantle
country: Australia
facility: Local Institution
state: Western Australia
city: Bruxelles
country: Belgium
facility: Local Institution
city: Leuven
country: Belgium
facility: Local Institution
city: Salvador
country: Brazil
facility: Local Institution
state: Bahia
city: Goiania
country: Brazil
facility: Local Institution
state: Goias
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Santo Andre - Sp
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Santos
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Kingston
country: Canada
facility: Local Institution
state: Ontario
city: London
country: Canada
facility: Local Institution
state: Ontario
city: Ottawa
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Levis
country: Canada
facility: Local Institution
state: Quebec
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Quebec
country: Canada
facility: Local Institution
city: Brno - Bohunice
country: Czech Republic
facility: Local Institution
city: Ceske Budejovice
country: Czech Republic
facility: Local Institution
city: Amiens Cedex 1
country: France
facility: Local Institution
city: Clichy
country: France
facility: Local Institution
city: Lille Cedex
country: France
facility: Local Institution
city: Nice
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pessac
country: France
facility: Local Institution
city: Toulouse
country: France
facility: Local Institution
city: Kiel
country: Germany
facility: Local Institution
city: Muenster
country: Germany
facility: Local Institution
city: Muenster
country: Germany
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Kochi
country: India
facility: Local Institution
state: Kerala
city: Mumbai
country: India
facility: Local Institution
state: Maharashtra
city: Bangalore
country: India
facility: Local Institution
city: Bangalore
country: India
facility: Local Institution
city: Delhi
country: India
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
city: Mangalore
country: India
facility: Local Institution
city: Manipal
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: Mysore
country: India
facility: Local Institution
city: Dublin 9
country: Ireland
facility: Local Institution
state: Dublin
city: Dublin
country: Ireland
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Padova
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: San Giovanni Rotondo
country: Italy
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Torreon
country: Mexico
facility: Local Institution
state: Coahuila
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico, D. F.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Culiacan
country: Mexico
facility: Local Institution
state: Sinaloa
city: Hermosillo
country: Mexico
facility: Local Institution
state: Sonora
city: Chihuahua
country: Mexico
facility: Local Institution
city: Amersfoort
country: Netherlands
facility: Local Institution
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Groningen
country: Netherlands
facility: Local Institution
city: Katowice
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Wroclaw
country: Poland
facility: Local Institution
city: Ponce
country: Puerto Rico
facility: Local Institution
city: Parktown West
country: South Africa
facility: Local Institution
state: Gauteng
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Overport
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Belville
country: South Africa
facility: Local Institution
state: Western Cape
city: Panorama
country: South Africa
facility: Local Institution
state: Western Cape
city: Bern
country: Switzerland
facility: Local Institution
city: Zuerich
country: Switzerland
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Oxford
country: United Kingdom
facility: Local Institution
state: Oxfordshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Sandborn WJ, Colombel JF, Sands BE, Rutgeerts P, Targan SR, Panaccione R, Bressler B, Geboes K, Schreiber S, Aranda R, Gujrathi S, Luo A, Peng Y, Salter-Cid L, Hanauer SB. Abatacept for Crohn's disease and ulcerative colitis. Gastroenterology. 2012 Jul;143(1):62-69.e4. doi: 10.1053/j.gastro.2012.04.010. Epub 2012 Apr 12.