A Study of Abatacept in Patients With Active Crohn's Disease
- Registration Number
- NCT00406653
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this clinical research study is to learn if abatacept can improve signs and symptoms of active Crohn's Disease in patients who have not had an adequate response to other therapies. The safety of this treatment will also be studied.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 451
- 18 years or older
- have had Crohn's Disease for at least 3 months
- moderate to severely active Crohn's Disease
- have had an inadequate response or intolerance to other Crohn's Disease treatments
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description 1 abatacept 4 arms for induction period 2 arms for maintenance period 2 placebo 4 arms for induction period 2 arms for maintenance period abatacept abatacept 1 arm for open-label extension phase
- Primary Outcome Measures
Name Time Method Open-Label Extension Period (OL); Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due to AEs Between Day OL-1 and Day OL-617 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.
Induction Period (IP); Number of Participants With Crohn's Disease Activity Index (CDAI)-Defined Clinical Response at Both Day IP-57 and Day IP-85 At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12). CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
Maintenance Period (MP); Number of Participants In CDAI-Defined Clinical Remission (CDAI <150) at Day MP-365 (12 Months) Day MP-365 (12 months) of maintenance therapy CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
OL; Number of Participants With Adverse Events (AEs) of Special Interest Between Day OL-1 and Day OL-617 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).
- Secondary Outcome Measures
Name Time Method MP; Number of Participants With Adverse Events (AEs) of Special Interest: Between Day IP-85 and Day MP-365 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).
MP; Number of Participants With Positive Antibody Response to Abatacept For participants not entering OL: All measurements 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) 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.
IP; Number of Participants With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
IP; Number of Participants Who Are Anti-TNF-Inadequate Responders/Anti-TNF Intolerant With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
MP; Number of Participants With CDAI-defined Clinical Response at Day MP-365. Day MP-365 CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
IP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due to AEs Day IP-1 through Day IP-85 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.
IP; Number of Participants With CDAI-Defined Clinical Response at Both Day IP-57 and Day IP-85 Among Participants With Inadequate Response and/or Intolerance to Anti-Tumor Necrosis Factor (TNF) At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
MP; Change From Baseline to Day MP-365 in Short Form-36 (SF-36) Baseline, Day MP-365 The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health; (2) mental component summary=vitality, social functioning, role-emotional, and mental health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value.
OL; Number of Participants With CDAI-defined Clinical Response or Clinical Remission at Day OL-365 Day OL-365 CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
IP; Number of Participants in CDAI-defined Clinical Remission at Both Day IP-57 and Day IP-85 (Key Secondary Outcome) At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
IP; Change From Baseline to Day IP-85 In Inflammatory Bowel Disease Questionnaire (IBDQ) Baseline, Day IP-85 The Inflammatory Bowel Disease Questionnaire (IBDQ) consists of a self-administered 32-item questionnaire evaluating quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. Responses 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 ranges between 32 to 224 with higher scores indicating a better quality of life. Change from Baseline= post-Baseline - Baseline value.
IP; Number of Participants With Adverse Events (AEs) of Special Interest Day IP-1 through Day IP-85 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).
MP; Number of Participants Who Were Not On Background Corticosteroid Therapy at Day MP-365 Among All Participants Who Received Baseline Corticosteroid Therapy Day MP-365 Participants who received corticosteroid therapy (e.g. prednisone or budesonide) were to maintain a stable dose until Day MP-1. On or after Day MP-1, a recommended tapering regimen of corticosteroid therapy was planned if the participant was in remission (i.e., CDAI score \< 150), or if the participant's condition had satisfactorily improved according to investigators clinical assessment. Other CD therapy was to remain at a stable dose throughout the Maintenance Period, with the exception of decreases due to drug-related toxicities.
IP; Number of Participants With Positive Antibody Response to Abatacept (ABA) 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) A electrochemiluminescent immunoassay screened sera for drug-specific antibodies, immunocompetition identified specific anti-ABA reactivity. Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Possibly immunoglobulin (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.
IP; Number of Participants in CDAI-Defined Clinical Remission at Both Day IP-57 and Day IP-85 Among Participants With Inadequate Response and/or Intolerance to Anti-TNF At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
MP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and Discontinuation Due To AEs Between Day IP-85 and Day MP-365 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.
MP; Number of Participants in CDAI-defined Clinical Remission at Both Day MP-169 and Day MP-365 Day MP-169 CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
MP; Number of Participants in CDAI-Defined Clinical Remission Among Participants With Inadequate Response and/or Intolerance to Anti-TNF Day MP-365 CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
OL; Number of Participants Who Were Not On Background Corticosteroid Therapy Among All Participants Who Received Baseline Corticosteroid Therapy Between Day OL-1 and Day OL-617 Background corticosteroid therapy included prednisone or budesonide.
MP; Change From Baseline to Day MP-365 in Inflammatory Bowel Disease Questionnaire (IBDQ) Baseline, Day MP-365 The Inflammatory Bowel Disease Questionnaire (IBDQ) consists of a self-administered 32-item questionnaire evaluating quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. Responses 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 ranges between 32 to 224 with higher scores indicating a better quality of life. Change from Baseline= post-baseline - Baseline value.
MP; Number of Participants Who Were Not On Background Corticosteroid Therapy at Day MP-365 Among Participants Who Received Baseline Corticosteroid Therapy and Who Achieved CDAI-Defined Clinical Remission Day MP-365 CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score is based partly on entries from participant's Diary (7 days before evaluation) which is kept while on study. CDAI scores range from 0 to \~600. Clinical response=CDAI reduction ≥100 or absolute CDAI \<150. Clinical remission=CDAI \<150. Moderate to severe disease=CDAI ≥220 and ≤450.
MP; Number of Participants With CDAI-Defined Clinical Response Among Participants With Inadequate Response and/or Intolerance to Anti-Tumor Necrosis Factor (TNF) Day MP-365 CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
OL; Number of Participants With CDAI-defined Clinical Response or Clinical Remission at Day OL-169 Day OL-169 CDAI is a composite index consisting of a weighted scoring of 8 disease variables:number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's Diary kept while on study. CDAI scores range from 0 to \~600 points. Clinical response=CDAI reduction ≥100 points or absolute CDAI \<150 points. Clinical remission=CDAI \<150 points. Moderate to severe disease=CDAI ≥220 and ≤450 points.
OL; Number of Participants With Positive Antibody Response to Abatacept 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) 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.
OL; Number of Participants With Pharmacogenomic Marker Activity Between Day OL-1 and Day OL-617 Changes in the expression of individual ribonucleic acid (RNA) transcripts were to be evaluated from whole blood using both microarray transcriptional profiling and quantitative polymerase chain reaction (PCR) methods. Peripheral RNA transcriptional profiling was to be used only to identify individual RNA transcripts that differ in expression with respect to time, treatment and outcome.
Trial Locations
- Locations (38)
Allegheny Center For Digestive Health
🇺🇸Pittsburgh, Pennsylvania, United States
Consultants For Clinical Research
🇺🇸Cincinnati, Ohio, United States
Nashville Medical Research
🇺🇸Nashville, Tennessee, United States
Gastroenterology Clinic Of San Antonio
🇺🇸San Antonio, Texas, United States
Health Science Center
🇺🇸Pratt, Kansas, United States
University Of Florida
🇺🇸Gainesville, Florida, United States
Vanderlick, Michael
🇺🇸Lafayette, Louisiana, United States
Gastroenterology Center Of The Midsouth, P.C.
🇺🇸Germantown, Tennessee, United States
University Of Alabama Medical Center
🇺🇸Birmingham, Alabama, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Borland-Groover Clinic
🇺🇸Jacksonville, Florida, United States
Shafran Gasteroenterology Center
🇺🇸Winter Park, Florida, United States
Atlanta Gastroenterology Associates
🇺🇸Atlanta, Georgia, United States
University Of Chicago Hospitals
🇺🇸Chicago, Illinois, United States
University Of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
Gulf Coast Research Assoc
🇺🇸Baton Rouge, Louisiana, United States
Minnesota Gastroenterology, P.A.
🇺🇸Plymouth, Minnesota, United States
Maryland Digestive Disease Research
🇺🇸Laurel, Maryland, United States
Aga Clinical Research Associates, Llc
🇺🇸Egg Harbor Twp, New Jersey, United States
Long Island Clinical Research
🇺🇸Great Neck, New York, United States
U Of Rochester Gastroenterology And Hepatology
🇺🇸Rochester, New York, United States
Mount Sinai School Of Medicine
🇺🇸New York, New York, United States
Charlotte Gastroenterology & Hepatology, Pllc
🇺🇸Charlotte, North Carolina, United States
Piedmont Medical Research Associates
🇺🇸Winston Salem, North Carolina, United States
Gastroenterology Specialists, Inc.
🇺🇸Canton, Ohio, United States
Gastrointestinal & Liver Diseases Consultants
🇺🇸Dayton, Ohio, United States
Options Health Research, Llc
🇺🇸Tulsa, Oklahoma, United States
Memphis Gastroenterology Group
🇺🇸Germantown, Tennessee, United States
Southeastern Clinical Research
🇺🇸Chattanooga, Tennessee, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Local Institution
🇨🇭Zuerich, Switzerland
University Endoscopy Center
🇺🇸Syracuse, New York, United States
Austin Gastroenterology, Pa
🇺🇸Austin, Texas, United States
The Permanente Medical Group, Inc
🇺🇸Sacramento, California, United States
Kansas City Gastroenterology And Hepatology
🇺🇸Kansas City, Missouri, United States
University Of North Carolina At Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University Of Louisville
🇺🇸Louisville, Kentucky, United States