A Study of Abatacept in Patients With Active Ulcerative Colitis

Phase 3

Completed

Conditions: Ulcerative Colitis

Interventions: Drug: abatacept
Drug: abatacept (ABA)
Drug: placebo

Registration Number: NCT00410410

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 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 591

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
abatacept	abatacept	1 arm for open-label extension phase (ABA \~10 mg/kg)
Abatacept (ABA)	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)
Placebo	placebo	1 arm for induction period 1 arm for maintenance period

Primary Outcome Measures

Name	Time	Method
Induction Period (IP); Number of Participants With Clinical Response (Per Mayo Score) at Week 12: IP Cohort 1 (IP1C)	Week 12 (Day IP-85)	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	Month 12 (Day MP-365)	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	Day OL-1 through the end of the OL	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	Day OL-1 through Day OL-729	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	Day OL-1 through Day OL-729	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	Day OL-1 through Day OL-729	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	Day OL-1 through Day OL-729	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	Day OL-1 through Day OL-729	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

Name	Time	Method
IP; Number of Participants With AEs Of Special Interest: IP1C + IP2C	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).
IP; Number of Participants With Physical Examination Findings: IP1C + IP2C	Day IP-1 through Day IP-85	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	Day IP-1 through Day IP-85	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	Day IP-1 through Day IP-85	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
OL; Number of Participants With Clinical Remission Over Time	Day OL-1 through Day OL-729	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	Open-Label Period (Day OL-1 through Day OL-729)	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 With Abatacept-Induced Antibodies	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).	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	Day MP-1 through 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 With AEs of Special Interest	Day MP-1 through 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 Physical Examination Findings	Day IP-85 through Day MP-365	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 Chemistry and Urinalysis Laboratory Abnormalities: IP1C	Day IP-1 through Day IP-85	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	Day IP-1 through Day IP-85	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	Day IP-1 through Day IP-85	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	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 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	Month 12 (Day MP-365)	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	Month 12 (Day MP-365)	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 With Marked Hematology Laboratory Abnormalities	Day IP-85 through Day MP-365	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
IP; Baseline Mayo Score: IP1C	Baseline	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	Week 12 (Day IP-85)	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	Week 12 (Day IP-85)	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	Week 12 (Day IP-85)	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	Baseline	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	Baseline (Day IP-1), Day IP-85 (Week 12)	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	Day IP-85 (Week 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.
IP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C	Day IP-85 (Week 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.
IP; Number of Participants With Mayo Physician Global Assessment (PGA) Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C	Day IP-85 (Week 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.
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	Week 12 (Day IP-85)	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	Week 12 (Day IP-85)	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	Week 12 (Day IP-85)	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 Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids and Achieved Clinical Remission by Month 12	Day MP-365 (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.
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	Last Study Visit (Day OL-729)	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	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 Using Corticosteroids During OL	Day OL-1 through Day OL-729	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.
MP; Mean Change From Baseline to Month 12 in IBDQ	Day MP-365	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)	Day MP-365	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	Day MP-365 (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.
IP; Number of Participants in Mucosal Healing at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C	Week 12 (Day IP-85)	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	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.
MP; Number of Participants With Clinical Response at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)	Month 12 (Day MP-365)	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)	Month 12 (Day MP-365)	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)	Month 12 (Day MP-365)	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 Marked Chemistry and Urinalysis Laboratory Abnormalities	Day IP-85 through Day MP-365	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
MP; Number of Participants in Clinical Remission at Both Month 6 and Month 12	Month 6 (Day MP-169), Month 12 (Day MP-365)	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 Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Month 12	Day MP-365 (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.
MP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Month 12	Day MP-365 (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.
MP; Number of Participants With Mayo PGA Subscores Indicating Mild Disease (≤1 Point) at Month 12	Day MP-365 (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.
OL; Number of Participants With Clinical Response Over Time	Day OL-1 through Day OL-729	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.

Trial Locations

Locations (51): Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
Atlanta Gastroenterology Associates
🇺🇸
Atlanta, Georgia, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Allegheny Center For Digestive Health
🇺🇸
Pittsburgh, Pennsylvania, United States
The Permanente Medical Group, Inc
🇺🇸
Sacramento, California, United States
University Of Kentucky Chandler Medical Center
🇺🇸
Lexington, Kentucky, United States
Gulf Coast Research
🇺🇸
Lafayette, Louisiana, United States
Shafran Gasteroenterology Center
🇺🇸
Winter Park, Florida, United States
Kansas City Gastroenterology And Hepatology
🇺🇸
Kansas City, Missouri, United States
Piedmont Medical Research Associates
🇺🇸
Winston Salem, North Carolina, United States
Charlotte Gastroenterology & Hepatology, Pllc
🇺🇸
Charlotte, North Carolina, United States
Gastroenterology Center Of The Midsouth, P.C.
🇺🇸
Germantown, Tennessee, United States
Memphis Gastroenterology Group
🇺🇸
Germantown, Tennessee, United States
University Of Louisville
🇺🇸
Louisville, Kentucky, United States
Mayo Clinic Arizona
🇺🇸
Scottsdale, Arizona, United States
University Of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
Local Institution
🇬🇧
Oxford, Oxfordshire, United Kingdom
University Of Alabama At Birmingham
🇺🇸
Birmingham, Alabama, United States
Miami Research Associates
🇺🇸
Miami, Florida, United States
Mayo Clinic Rochester
🇺🇸
Rochester, Minnesota, United States
Oklahoma Foundation For Digestive Research
🇺🇸
Oklahoma City, Oklahoma, United States
Consultants For Clinical Research, Inc.
🇺🇸
Cincinnati, Ohio, United States
Nashville Medical Research
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Nashville, Tennessee, United States
Alamo Medical Research
🇺🇸
San Antonio, Texas, United States
Center For Digestive & Liver Diseases, Inc.
🇺🇸
Mexico, Missouri, United States
Litchfield County Gastroenterology Assoc.
🇺🇸
Torrington, Connecticut, United States
University Of Florida
🇺🇸
Gainesville, Florida, United States
Borland-Groover Clinic
🇺🇸
Jacksonville, Florida, United States
Western States Clinical Research Inc.
🇺🇸
Wheatridge, Colorado, United States
Hanover Medical Specialists, P.A.
🇺🇸
Wilmington, North Carolina, United States
Medical University Of South Carolina
🇺🇸
Charleston, South Carolina, United States
Hudson Valley Medical Research Llc
🇺🇸
Fishkill, New York, United States
Clinical Pharmacology Study Group
🇺🇸
Worcester, Massachusetts, United States
Healthcare Research Consultants
🇺🇸
Tulsa, Oklahoma, United States
Tacoma Digestive Disease Research Ctr.
🇺🇸
Tacoma, Washington, United States
Mount Sinai School Of Medicine
🇺🇸
New York, New York, United States
Gastrointestinal Resrch Assoc.
🇺🇸
Setauket, New York, United States
Aga Clinical Research Associates, Llc
🇺🇸
Egg Harbor Twp, New Jersey, United States
Health Science Center
🇺🇸
Pratt, Kansas, United States
Austin Gastroenterology, Pa
🇺🇸
Austin, Texas, United States
Good, Larry I.
🇺🇸
Rockville Centre, New York, United States
Options Health Research, Llc
🇺🇸
Tulsa, Oklahoma, United States
Long Island Clinical Research
🇺🇸
Great Neck, New York, United States
University Of Rochester Medical Center
🇺🇸
Rochester, New York, United States
Gastrointestinal & Liver Diseases Consultants
🇺🇸
Dayton, Ohio, United States
University Of Chicago Hospitals
🇺🇸
Chicago, Illinois, United States
Minnesota Gastroenterology, P.A.
🇺🇸
Plymouth, Minnesota, United States
Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
Gastroenterology Specialists, Inc.
🇺🇸
Canton, Ohio, United States
Gastroenterology Clinic Of San Antonio
🇺🇸
San Antonio, Texas, United States
Hospital Of The University Of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States