A Study of Abatacept in Patients With Active Crohn's Disease

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.

Time frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12).

Population: All Randomized and Treated (receiving ≥1 infusion) Participants in Induction Period. Due to site non-compliance with the study protocol, 1 randomized and treated participant from Site 166 was excluded.

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.

Time frame: Day MP-365 (12 months) of maintenance therapy

Population: All Randomized and Treated (receiving ≥1 infusion) Participants in Maintenance Period. The Maintenance Period was not sized based on power considerations, and thus, no formal statistical hypothesis testing was performed.

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).

Time frame: Between Day OL-1 and Day OL-617

Population: All participants who received at least 1 infusion of open-label study medication at any time, based on a participant's received treatment (As Treated Analysis Population)

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.

Time frame: Between Day OL-1 and Day OL-617

Population: All participants who received at least 1 infusion of open-label study medication at any time, based on a participant's received treatment (As Treated Analysis Population). The OL was not sized based on power considerations.

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.

Time frame: Baseline, Day IP-85

Population: All Randomized and Treated (receiving ≥1 infusion) Participants in Induction Period with both Baseline and post-Baseline measurements.

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.

Time frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy

Population: Participants in the All Randomized and Treated (receiving ≥1 infusion) Population who in the past had an inadequate response to, or who were intolerant to, an approved anti-TNF agent at an approved labeled dose for at least 8 weeks. Due to site non-compliance with the study protocol, 1 randomized and treated participant from Site 166 was excluded.

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.

Time frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy

Population: All Randomized and Treated (receiving ≥1 infusion) Participants in Induction Period

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.

Time frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy

Population: Participants in the All Randomized and Treated (receiving ≥1 infusion) Population who in the past had an inadequate response to, or who were intolerant to, an approved anti-TNF agent at an approved labeled dose for at least 8 weeks. Due to site non-compliance with the study protocol, 1 randomized and treated participant from Site 166 was excluded.

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).

Time frame: Day IP-1 through Day IP-85

Population: All participants who received at least 1 infusion of study medication during the IP, based on a participant's received treatment (As Treated Analysis Population)

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.

Time frame: Day IP-1 through Day IP-85

Population: All participants who received at least 1 infusion of study medication during the Induction Period, based on a participant's received treatment (As Treated Analysis Population)

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.

Time frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy

Population: Participants in the All Randomized and Treated (receiving ≥1 infusion) Population who in the past had an inadequate response to, or who were intolerant to, an approved anti-TNF agent at an approved labeled dose for at least 8 weeks. Due to site non-compliance with the study protocol, 1 randomized and treated participant from Site 166 was excluded.

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.

Time frame: At both Day IP-57 (Wk 8) and Day IP-85 (Wk 12) of induction therapy

Population: All Randomized and Treated (receiving ≥1 infusion) Participants in Induction Period

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.

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)

Population: All participants who received abatacept and for whom baseline and at least 1 additional measurement were available were included in the Immunogenicity Analysis Population.

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.

Time frame: Baseline, Day MP-365

Population: Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis for changes from baseline in IBDQ responses were not conducted for the MP as planned.

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.

Time frame: Baseline, Day MP-365

Population: Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis for changes from baseline in SF-36 responses were not conducted for the MP as planned.

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.

Time frame: Day MP-365

Population: Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint subgroup analysis of clinical remission in participants who have had an inadequate response and/or intolerance to anti-TNF therapy was not conducted for the MP as planned.

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.

Time frame: Day MP-169

Population: Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis for the cohort of participants with clinical remission at both Day MP-169 and Day MP-365 was not conducted for the MP as planned.

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.

Time frame: Day MP-365

Population: On/after Day MP-1, a recommended tapering of corticosteroids was planned if participant was in remission/had improved. Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analyses for corticosteroid sparing were not conducted for the MP as planned

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.

Time frame: Day MP-365

Population: On/after Day MP-1, a defined tapering of corticosteroids was planned if the participant was in remission/had improved. Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analyses for corticosteroid sparing were not conducted for the MP as planned.

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).

Time frame: Between Day IP-85 and Day MP-365

Population: All participants who received at least 1 infusion of study medication during the MP, based on a participant's received treatment (As Treated Analysis Population)

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.

Time frame: Between Day IP-85 and Day MP-365

Population: All participants who received at least 1 infusion of study medication during the Maintenance Period, based on a participant's received treatment (As Treated Analysis Population)

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.

Time frame: Day MP-365

Population: Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint subgroup analysis of clinical response in participants who have had an inadequate response and/or intolerance to anti-TNF therapy was not conducted for the MP as planned.

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.

Time frame: Day MP-365

Population: All Randomized and Treated (receiving ≥1 infusion) Participants in Maintenance Period. Due to site non-compliance with the study protocol, 1 randomized and treated participant from Site 166 was excluded.

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.

Time frame: 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)

Population: All participants who received abatacept and for whom baseline and at least 1 additional measurement were available were included in the Immunogenicity Analysis Population. The placebo group was constituted by participants who received abatacept in the IP and underwent drug withdrawal in the MP.

Background corticosteroid therapy included prednisone or budesonide.

Time frame: Between Day OL-1 and Day OL-617

Population: Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis of corticosteroid use in participants was not conducted for the OL as planned.

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.

Time frame: Day OL-169

Population: All Randomized and Treated (receiving ≥1 infusion) Participants in Open-Label Extension Period.

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.

Time frame: Day OL-365

Population: All Randomized and Treated (receiving ≥1 infusion) Participants in Open-Label Extension Period.

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.

Time frame: Between Day OL-1 and Day OL-617

Population: Due to the early termination of the study after the IP results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis of pharmacogenomic marker activity in participants was not conducted for the OL as planned.

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.

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)

Population: All participants who received abatacept and for whom baseline and at least 1 additional measurement were available were included in the Immunogenicity Analysis Population.