Trial record 1 of 1 for:    ulcerative colitis abatacept
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A Study of Abatacept in Patients With Active Ulcerative Colitis

This study has been completed.
Sponsor:
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00410410
First received: December 11, 2006
Last updated: November 4, 2010
Last verified: November 2010
  Purpose

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


Condition Intervention Phase
Ulcerative Colitis
Drug: abatacept (ABA)
Drug: placebo
Drug: abatacept
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Induction Period (IP); Number of Participants With Clinical Response (Per Mayo Score) at Week 12: IP Cohort 1 (IP1C) [ Time Frame: Week 12 (Day IP-85) ] [ Designated as safety issue: No ]
    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.

  • Maintenance Period (MP); Number of Participants With Clinical Response (Per Mayo Score) at Month 12 [ Time Frame: Month 12 (Day MP-365) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day OL-1 through the end of the OL ] [ Designated as safety issue: Yes ]
    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.

  • OL; Number of Participants With AEs of Special Interest [ Time Frame: Day OL-1 through Day OL-729 ] [ Designated as safety issue: Yes ]
    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).

  • OL; Number of Participants With Physical Examination Findings [ Time Frame: Day OL-1 through Day OL-729 ] [ Designated as safety issue: Yes ]
    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).

  • OL; Number of Participants With Marked Hematology Laboratory Abnormalities [ Time Frame: Day OL-1 through Day OL-729 ] [ Designated as safety issue: Yes ]
    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.

  • OL; Number of Participants With Liver and Kidney Function and Electrolyte Laboratory Abnormalities [ Time Frame: Day OL-1 through Day OL-729 ] [ Designated as safety issue: Yes ]
    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

  • OL; Number of Participants With Chemistry and Urinalysis Laboratory Abnormalities [ Time Frame: Day OL-1 through Day OL-729 ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • IP; Baseline Mayo Score: IP1C [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    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.

  • IP; Number of Participants in Clinical Remission (Per Mayo Score) at Week 12: IP1C [ Time Frame: Week 12 (Day IP-85) ] [ Designated as safety issue: No ]
    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.

  • IP; Number of Participants in Mucosal Healing (Per Mayo Score) at Week 12: IP1C [ Time Frame: Week 12 (Day IP-85) ] [ Designated as safety issue: No ]
    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

  • IP; Number of Participants With Clinical Response (Per Mayo Score) at Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C [ Time Frame: Week 12 (Day IP-85) ] [ Designated as safety issue: No ]
    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.

  • IP; Baseline Inflammatory Bowel Disease Questionnaire (IBDQ) Score: IP1C [ Time Frame: Baseline ] [ Designated as safety issue: Yes ]
    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.

  • IP; Mean Change From Baseline To Week 12 in Inflammatory Bowel Disease Questionnaire (IBDQ): IP1C [ Time Frame: Baseline (Day IP-1), Day IP-85 (Week 12) ] [ Designated as safety issue: No ]
    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.

  • IP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C [ Time Frame: Day IP-85 (Week 12) ] [ Designated as safety issue: No ]
    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.

  • IP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C [ Time Frame: Day IP-85 (Week 12) ] [ Designated as safety issue: No ]
    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.

  • IP; Number of Participants With Mayo Physician Global Assessment (PGA) Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C [ Time Frame: Day IP-85 (Week 12) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Week 12 (Day IP-85) ] [ Designated as safety issue: No ]
    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.

  • IP; Number of Participants With Clinical Response At Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C [ Time Frame: Week 12 (Day IP-85) ] [ Designated as safety issue: No ]
    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.

  • IP; Number of Participants in Clinical Remission at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C [ Time Frame: Week 12 (Day IP-85) ] [ Designated as safety issue: No ]

    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.


  • IP; Number of Participants in Mucosal Healing at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C [ Time Frame: Week 12 (Day IP-85) ] [ Designated as safety issue: No ]
    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.

  • IP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation: IP1C + IP2C [ Time Frame: Day IP-1 through Day IP-85 ] [ Designated as safety issue: Yes ]
    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 AEs Of Special Interest: IP1C + IP2C [ Time Frame: Day IP-1 through Day IP-85 ] [ Designated as safety issue: Yes ]
    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).

  • IP; Number of Participants With Physical Examination Findings: IP1C + IP2C [ Time Frame: Day IP-1 through Day IP-85 ] [ Designated as safety issue: Yes ]
    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).

  • IP; Number of Participants With Marked Hematology Laboratory Abnormalities: IP1C [ Time Frame: Day IP-1 through Day IP-85 ] [ Designated as safety issue: Yes ]
    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.

  • IP; Number of Participants With Marked Liver and Kidney Function and Electrolyte Laboratory Abnormalities: IP1C [ Time Frame: Day IP-1 through Day IP-85 ] [ Designated as safety issue: Yes ]
    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

  • IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP1C [ Time Frame: Day IP-1 through Day IP-85 ] [ Designated as safety issue: Yes ]
    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

  • IP; Number of Participants With Marked Hematology, Liver and Kidney Function, and Electrolyte Laboratory Abnormalities: IP2C [ Time Frame: Day IP-1 through Day IP-85 ] [ Designated as safety issue: Yes ]
    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;

  • IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP2C [ Time Frame: Day IP-1 through Day IP-85 ] [ Designated as safety issue: Yes ]
    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

  • IP; Number of Participants With Abatacept-Induced Antibodies: IP1C + IP2C [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants in Clinical Remission at Month 12 [ Time Frame: Month 12 (Day MP-365) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (≤1 Point) at Month 12 [ Time Frame: Month 12 (Day MP-365) ] [ Designated as safety issue: No ]
    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

  • MP; Number of Participants in Clinical Remission at Both Month 6 and Month 12 [ Time Frame: Month 6 (Day MP-169), Month 12 (Day MP-365) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids and Achieved Clinical Remission by Month 12 [ Time Frame: Day MP-365 (Month 12) ] [ Designated as safety issue: No ]
    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.

  • MP; Mean Change From Baseline to Month 12 in IBDQ [ Time Frame: Day MP-365 ] [ Designated as safety issue: No ]
    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.

  • MP; Mean Change From Baseline to Month 12 in Short Form-36 (SF-36) [ Time Frame: Day MP-365 ] [ Designated as safety issue: No ]
    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).

  • MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids for 90 Consecutive Days and Achieved Clinical Remission by Month 12 [ Time Frame: Day MP-365 (Month 12) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Month 12 [ Time Frame: Day MP-365 (Month 12) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Month 12 [ Time Frame: Day MP-365 (Month 12) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Mayo PGA Subscores Indicating Mild Disease (≤1 Point) at Month 12 [ Time Frame: Day MP-365 (Month 12) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Clinical Response at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab) [ Time Frame: Month 12 (Day MP-365) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Clinical Remission at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab) [ Time Frame: Month 12 (Day MP-365) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Clinical Mucosal Healing at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab) [ Time Frame: Month 12 (Day MP-365) ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Abatacept-Induced Antibodies [ Time Frame: 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). ] [ Designated as safety issue: No ]
    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.

  • MP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation [ Time Frame: Day MP-1 through Day MP-365 ] [ Designated as safety issue: Yes ]
    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 With AEs of Special Interest [ Time Frame: Day MP-1 through Day MP-365 ] [ Designated as safety issue: Yes ]
    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 Physical Examination Findings [ Time Frame: Day IP-85 through Day MP-365 ] [ Designated as safety issue: Yes ]
    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).

  • MP; Number of Participants With Marked Hematology Laboratory Abnormalities [ Time Frame: Day IP-85 through Day MP-365 ] [ Designated as safety issue: Yes ]
    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

  • MP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities [ Time Frame: Day IP-85 through Day MP-365 ] [ Designated as safety issue: Yes ]
    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

  • OL; Number of Participants With Clinical Response Over Time [ Time Frame: Day OL-1 through Day OL-729 ] [ Designated as safety issue: No ]
    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.

  • OL; Number of Participants With Clinical Remission Over Time [ Time Frame: Day OL-1 through Day OL-729 ] [ Designated as safety issue: No ]
    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.

  • OL; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (≤1 Point) During OL [ Time Frame: Open-Label Period (Day OL-1 through Day OL-729) ] [ Designated as safety issue: No ]
    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

  • 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 [ Time Frame: Last Study Visit (Day OL-729) ] [ Designated as safety issue: No ]
    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.

  • OL; Number of Participants With Abatacept-Induced Antibodies [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 Using Corticosteroids During OL [ Time Frame: Day OL-1 through Day OL-729 ] [ Designated as safety issue: No ]
    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.


Enrollment: 591
Study Start Date: December 2006
Study Completion Date: November 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abatacept (ABA)

Induction Period; 3 arms for Cohort 1: ABA 30/~10 mg/kg (ABA administered at 30 mg/kg followed by ABA at ~10 mg/kg), ABA ~10 mg/kg, ABA 3 mg/kg

Induction Period; 2 arms for Cohort 2: ABA 30/~10 mg/kg and Second Cohort ABA ~10 mg/kg

1 arm for maintenance period (ABA ~10 mg/kg)

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

Other Names:
  • Orencia
  • BMS-188667
Placebo Comparator: Placebo

1 arm for induction period

1 arm for maintenance period

Drug: placebo

Normal saline, IV, 0 mg/kg, every 28 days.

Induction Period 3 months

Maintenance Period 12 months

abatacept
1 arm for open-label extension phase (ABA ~10 mg/kg)
Drug: 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

Other Names:
  • Orencia
  • BMS-188667

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00410410

  Show 144 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00410410     History of Changes
Other Study ID Numbers: IM101-108
Study First Received: December 11, 2006
Results First Received: August 12, 2010
Last Updated: November 4, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colitis
Colitis, Ulcerative
Ulcer
Abatacept
Colonic Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
Pathologic Processes
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014