Evaluation of Efficacy and Safety of Brazikumab (MEDI2070) in Participants With Active, Moderate to Severe Crohn's Disease

CDAI remission was defined as a CDAI score of \<150 at Week 8. CDAI score was calculated by summing weighted scores for subjective items \[number of liquid or very soft stools, abdominal pain (on a scale of 0=none to 3=severe) and general well-being (on a scale of 1=generally well to 4=terrible)\] recorded by a diary during a 1-week period, and objective items \[associated symptoms, taking antidiarrheal agents such as loperamide/opiates, abdominal mass, hematocrit, daily morning temperature, and body weight\]. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Time frame: Week 8

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period.

Laboratory parameters included tests for hematology, serum chemistry and urinalysis. Laboratory values that were outside the reference range, considered clinically significant were reported.

Time frame: From first dose of study drug up to 28 weeks post last dose (approximately up to Week 80)

Population: Safety population included all participants who received at least 1 dose of investigational product.

Time frame: Predose at Weeks 0, 4, 12, 16, 28, 40 and 52

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period. Number analyzed is number of participants with evaluable data at given time-point.

An AE is any untoward medical occurrence in a patient/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. An adverse event can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not related to the investigational product. A TEAE is any new AE or worsening of an existing condition after initiation of treatment. An SAE is an AE that resulted in death, inpatient hospitalization/prolongation of existing hospitalization, persistent or significant disability or incapacity, life threatening, a congenital anomaly/birth defect, or an important medical event. AE of special interest were infusion/injection-site reactions, hypersensitivity reactions, malignancies, cardiac events like myocardial infarction, stroke/cardiovascular death, ocular AE including cataracts.

Time frame: From first dose of study drug up to 28 weeks post last dose (approximately up to Week 80)

Population: Safety population included all participants who received at least 1 dose of investigational product.

Abdominal pain remission is defined as no daily score \> 2 on an 11-point (0 to 10) pain scale during 1 week, where 0 = no pain and 10 = worst imaginable pain.

Time frame: Weeks 8, 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period. Participant with missing data for this outcome measure was imputed as a non-responder.

Abdominal pain response is defined as a ≥ 30% reduction in weekly pain score from baseline on an 11-point (0 to 10) pain scale, where 0 = no pain and 10 = worst imaginable pain.

Time frame: Baseline; Weeks 8, 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period. Participant with missing data for this outcome measure was imputed as a non-responder.

CDAI clinical remission was defined as a CDAI score of \<150. CDAI score was calculated by summing weighted scores for subjective items \[number of liquid or very soft stools, abdominal pain (on a scale of 0=none to 3=severe) and general well-being (on a scale of 1=generally well to 4=terrible)\] recorded by a diary during a 1-week period, and objective items \[associated symptoms, taking antidiarrheal agents such as loperamide/opiates, abdominal mass, hematocrit, daily morning temperature, and body weight\]. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Time frame: Weeks 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period.

CDAI modified sustained clinical remission was defined as a CDAI score of \<150 at both Weeks 8 and 28. CDAI score was calculated by summing weighted scores for subjective items \[number of liquid or very soft stools, abdominal pain (on a scale of 0=mild to 3=severe) and general well-being (on a scale of 1=generally well to 4=terrible)\] recorded by a diary during a 1-week period, and objective items \[associated symptoms, taking antidiarrheal agents such as loperamide/opiates, abdominal mass, hematocrit, daily morning temperature and body weight\]. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Time frame: Weeks 8 and 28

Population: Data was not collected for this endpoint.

CDAI response was defined as a decrease from baseline in the CDAI score of ≥100. CDAI score was calculated by summing weighted scores for subjective items \[number of liquid or very soft stools, abdominal pain (on a scale of 0=none to 3=severe) and general well-being (on a scale of 1=generally well to 4=terrible)\] recorded by a diary during a 1-week period, and objective items \[associated symptoms, taking antidiarrheal agents such as loperamide/opiates, abdominal mass, hematocrit, daily morning temperature, and body weight\]. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Time frame: Baseline, Weeks 8, 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period. Participant with missing data for this outcome measure was imputed as a non-responder.

Loose/liquid stool frequency response is the stools identified as Type 6 or 7 on Bristol Stool Form Scale, ≥ 30% reduction in weekly loose/liquid stool count compared to baseline. The participant recorded their stool consistency each day in a daily patient diary using the Bristol Stool Form Scale. It is a scale between 1-7, it measured the shape of the stool, where 1 correlates with the firmest stool and 7 correlates with entirely liquid stool.

Time frame: Baseline, Weeks 8, 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period. Participant with missing data for this outcome measure was imputed as a non-responder.

Loose/liquid stool frequency response is the stools identified as Type 6 or 7 on Bristol Stool Form Scale, ≥ 30% reduction in weekly loose/liquid stool count compared to baseline. The participant recorded their stool consistency each day in a daily patient diary using the Bristol Stool Form Scale. It is a scale between 1-7, it measured the shape of the stool, where 1 correlates with the firmest stool and 7 correlates with entirely liquid stool.

Time frame: Baseline, Weeks 8, 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period. Participant with missing data for this outcome measure was imputed as a non-responder.

PRO2 evaluated 2 patient-reported symptoms: the frequency of liquid or soft stools and abdominal pain (on an 11-point scale where 0=no pain to 10=worst imaginable pain). A weekly score was calculated for the liquid or soft stool frequency and a separate weekly score was calculated for abdominal pain, in each case based on daily symptom reporting. PRO2-remission was defined as PRO2 less than 8 points. PRO2 is a composite index consisting of weighted scoring of both variables. PRO2 scores ranges from 0 to approximately 45, higher score indicates higher disease activity.

Time frame: Weeks 8, 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period.

PRO2 evaluated 2 patient-reported symptoms: the frequency of liquid or soft stools and abdominal pain. PRO2 response was defined as remission or response in one symptom (either abdominal pain or stool frequency) plus response in the other: a) abdominal pain remission: On an 11-point (0 to 10) pain scale: During 1 week, no daily score \> 2, b) abdominal pain response: On an 11-point (0 to 10) pain scale: ≥ 30% reduction in weekly pain score from baseline, c) loose/liquid stool frequency remission: Counting stools identified as Type 6 or 7 on Bristol Stool Form Scale (BSFS), (The BSFS is a scale between 1-7, where 1 correlates with the firmest stool and 7 correlates with entirely liquid stool), during 1 week, each daily loose/liquid stool count ≤ 3, d) loose/liquid stool frequency response: Counting stools identified as Type 6 or 7 on BSFS, ≥ 30% reduction in weekly loose/liquid stool count compared to baseline.

Time frame: Baseline, Weeks 8, 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period.

SES-CD remission was defined as a Total SES-CD score of ≤4 and no subscore \>2. The SES-CD evaluates 4 endoscopic variables \[ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis\] each rated from 0 (best) to 3 (worst) in 5 segments evaluated during ileocolonoscopy \[ileum, right colon, transverse colon, left colon, and rectum\]. The score for each endoscopic variable is the sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 60, where higher scores indicates more severe disease.

Time frame: Weeks 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period. Participant with missing data for this outcome measure was imputed as a non-responder.

SES-CD response was defined as a decrease from baseline in SES-CD score of ≥ 50%. The SES-CD evaluates 4 endoscopic variables \[ulcer size, proportion of the surface area that is ulcerated, proportion of the surface area affected, and stenosis\] each rated from 0 (best) to 3 (worst) in 5 segments evaluated during ileocolonoscopy \[ileum, right colon, transverse colon, left colon, and rectum\]. The score for each endoscopic variable is the sum of values obtained for each segment. The SES-CD total is the sum of the 4 endoscopic variable scores from 0 to 60, where higher scores indicates more severe disease.

Time frame: Baseline, Weeks 16 and 28

Population: ITT population included all participants who were randomized into the study and received at least 1 whole dose of investigational product for the 28-week, double-blind, placebo-controlled treatment period. Participant with missing data for this outcome measure was imputed as a non-responder.

Time frame: Predose at Weeks 0, 1, 4, 8, 12, 16, 28; Postdose at Weeks 0 and 4

Population: The Pharmacokinetic (PK) population included all participants who received at least 1 dose of investigational product and had at least 1 PK sample containing quantifiable brazikumab. Number analyzed is number of participants with evaluable data at given time-point.

Time frame: Weeks 16 and 28

Population: Data for predictive biomarker analysis was not collected due to small number of participants available for analysis.