Digestive System Diseases

All Conditions

Symptoms and General Pathology

Crohn Disease

Intestinal Diseases

Inflammatory Bowel Diseases

Necrosis

Gastroenteritis

Gastrointestinal Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunologic Factors

Placebo-matching brazikumab intravenous (IV) infusion and subcutaneous (SC) injection at Weeks 0 and 4 followed by placebo-matching brazikumab SC injection at Weeks 8 and 12 in the induction phase and at Weeks 16, 20 and 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection every 4 weeks up to Week 48 in the open-label period.

Brazikumab 700 mg, IV infusion and placebo-matching brazikumab, SC injection at Weeks 0 and 4 followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.

Brazikumab 280 mg, IV infusion and placebo-matching brazikumab, SC injection at Week 0 followed by brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.

Brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 105 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 105 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 105 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.

Brazikumab 70 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 35 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 35 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 35 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.

Brazikumab IV infusion as per protocol specified dosing schedule.

Brazikumab IV Infusion

Brazikumab SC Injection

Placebo-matching Brazikumab IV infusion as per protocol specified dosing schedule.

Placebo

A Phase 2b study to evaluate the efficacy and safety of brazikumab (MEDI2070) in participants with moderate to severe Crohn's disease who have failed or are intolerant to anti-tumor necrosis factor-alpha (anti-TNFα) therapy.

This is a four-part Phase 2b study comprised of a 16-week, double-blind, placebo-controlled, Induction Period, a 12-week double-blind, placebo-controlled, Maintenance Period, a 24-week, Open-label Period and a post-treatment 28 week observational safety follow-up period designed to evaluate the short-term efficacy and the short- and long term safety of brazikumab in participants with moderate to severe, active Crohn's disease (CD) who have failed or are intolerant to anti-TNFα therapy as determined by the Investigator.

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

A Phase 2b Double-Blind, Multi-Dose, Placebo-Controlled Study to Evaluate the Efficacy and Safety of MEDI2070 in Subjects With Moderate to Severe Crohn's Disease Who Have Failed or Are Intolerant to Anti-tumor Necrosis Factor-alpha Therapy

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

AstraZeneca

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

Placebo-matching brazikumab intravenous (IV) infusion and subcutaneous (SC) injection at Weeks 0 and 4 followed by placebo-matching brazikumab SC injection at Weeks 8 and 12 in the induction phase and at Weeks 16, 20 and 24 in the maintenance phase.

DB: Placebo

Brazikumab 700 mg, IV infusion and placebo-matching brazikumab, SC injection at Weeks 0 and 4 followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks at Weeks 8 and 12 in the induction phase and Weeks 16, 20 and 24 in the maintenance phase.

DB: Brazikumab High Dose

Brazikumab 280 mg, IV infusion and placebo-matching brazikumab, SC injection at Week 0 followed by brazikumab 210 mg, SC injection and placebo-matching brazikumab IV infusion at Week 4, followed by brazikumab 210 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase.

DB: Brazikumab High-Medium Dose

Brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 105 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 105 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 105 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase.

DB: Brazikumab Low-Medium Dose

Brazikumab 70 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 0 followed by brazikumab 35 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 35 mg, SC injection at Weeks 8 and 12 in the induction phase. Participants received brazikumab 35 mg, SC injection every 4 weeks up to Week 24 in the maintenance phase.

DB: Brazikumab Low Dose

Brazikumab 210 mg, SC injection every 4 weeks in the open-label period starting at Week 28 up to Week 48. Participants received placebo-matching brazikumab in the double-blind treatment period.

OL: Placebo/Brazikumab 210 mg

Brazikumab 210 mg, SC injection every 4 weeks in the open-label period starting at Week 28 up to Week 48. Participants received high dose of brazikumab in the double-blind treatment period.

OL: Brazikumab High Dose/Brazikumab 210 mg

Brazikumab 210 mg, SC injection every 4 weeks in the open-label period starting at Week 28 up to Week 48. Participants received high-medium dose of brazikumab in the double-blind treatment period.

OL: Brazikumab High-Medium Dose/Brazikumab 210 mg

Brazikumab 210 mg, SC injection every 4 weeks in the open-label period starting at Week 28 up to Week 48. Participants received low-medium dose of brazikumab in the double-blind treatment period.

OL: Brazikumab Low-Medium Dose/Brazikumab 210 mg

Brazikumab 210 mg, SC injection every 4 weeks in the open-label period starting at Week 28 up to Week 48. Participants received low dose of brazikumab in the double-blind treatment period.

OL: Brazikumab Low Dose/Brazikumab 210 mg

Brazikumab High Dose

Brazikumab 280 mg, IV infusion and placebo-matching brazikumab, SC injection at Week 0 followed by brazikumab 210 mg, SC injection and placebo-matching brazikumab, IV infusion at Week 4, followed by brazikumab 210 mg, SC injection in the induction phase. Participants received brazikumab 210 mg, SC injection every 4 weeks in the maintenance phase and open-label period up to Week 48.

Brazikumab High-Medium Dose

Brazikumab Low-Medium Dose

Brazikumab Low Dose

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Intent-to-treat (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.

Due to small number of participants,29 randomized by study termination, only descriptive statistics for limited efficacy endpoints were provided. Enrollment did not achieve target power and was insufficient to produce statistically reliable results.

Clinical Study Information Center

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.

Percentage of Participants With Crohn's Disease Activity Index (CDAI) Remission at Week 8

Week 8

Week 16

Week 28

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.

Percentage of Participants With Loose/Liquid Stool Frequency Response

Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response

Percentage of Participants With CDAI Clinical Remission

Percentage of Participants With Simple Endoscopic Score for Crohn's Disease (SES-CD) Response

Weeks 28

Percentage of Participants With Loose/Liquid Stool Frequency Remission

Percentage of Participants With Simple Endoscopic Score for Crohn's Disease (SES-CD) Remission

Percentage of Participants With Patient Response Outcome-2 (PRO2) Remission

Percentage of Participants With PRO2 Response

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

Serum Interleukin (IL)-22 and Serum Lipocalin 2 (LCN2) Concentration as a Biomarker of Brazikumab's Efficacy

Data was not collected for this endpoint.

Percentage of Participants With CDAI Modified Sustained Clinical Remission at Both Weeks 8 and 28

Week 0, Predose

Week 0, Postdose

Week 1, Predose

Week 4, Predose

Week 4, Postdose

Week 8, Predose

Week 12, Predose

Week 16, Predose

Week 28, Predose

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.

Serum Brazikumab Concentration

Week 0

Week 4

Week 12

Week 40

Week 52

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.

Number of Participants With Serum Anti-drug Antibodies for Brazikumab

TEAEs

TESAEs

TEAEs of Special Interest

TEAEs Leading to Discontinuation

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), TEAEs of Special Interest and TEAEs Leading to Discontinuation

Number of Participants With Clinically Significant Laboratory Values

Percentage of Participants With Abdominal Pain Response

Percentage of Participants With Abdominal Pain Remission

Double Blind (DB): Placebo

Open-label (OL): Placebo/Brazikumab 210 mg

OL: Brazikumab High- Medium Dose/Brazikumab 210 mg

Double-blind Period

Open-label (OL) Period

MEDI2070 sc injection; open-label arm is available for all subjects upon completion of first placebo-controlled treatment period

MEDI2070

placebo

The study is designed to evaluate the clinical efficacy and safety of MEDI2070 as compared to placebo. Investigational product will be administered as intravenous infusion in double-blind period, and as a subcutaneous injection in open-label period

This is a two-part Phase 2a study compromising a 12-week, double-blind, placebo-controlled, treatment period followed by a 100-week, open label, treatment period to evaluate short-term efficacy, and the short- and long-term safety of MEDI2070 in subjects with moderate to severe, active CD who have failed or are intolerant to anti-TNFα therapy as determined by the investigator. Approximately 120 subjects will be randomized in a 1:1 ratio to initially receive a fixed IV dose of MEDI2070 or placebo on Week 0(Day1) and Week 4 (Day 29) during the 12-week, double-blind, placebo-controlled, treatment period. At the completion of the double-blind, placebo-controlled, treatment period (Week 12), subjects will have the option to enter a 100-week, open-label, treatment period where they will receive open-label MEDI2070 (SC) Q4W (Week 12 through Week 112). Subjects will be followed for safety at 3 visits over 28 weeks after their last dose of IP. Subjects will also be contacted by phone 36 weeks after their last dose of IP for safety.

Evaluation of Efficacy and Safety of MEDI2070 in Patients With Active, Moderate-to-severe Crohn's Disease.

A Phase 2a Study to Evaluate the Efficacy and Safety of MEDI2070 in Subjects With Moderate to Severe Crohn's Disease Who Have Failed or Are Intolerant to Anti-tumor Necrosis Factor-alpha Therapy

A CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days includes subject reported symptoms, physician-assessed signs, and laboratory markers. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity. The CDAI response at Week 8 is defined as either CDAI score of less than (\<)150 or CDAI reduction from baseline of at least 100 points, where baseline was last non-missing observation prior to first administration of the study drug. Modified Intent-to-treat (mITT)population was analysed for this end point, which included all subjects who were randomized and received at least 1 dose of study drug in double-blind period.

The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. CDAI 70-point improvement is defined as a reduction from baseline in CDAI score of at least 70 points/scores, where baseline was the latest nonmissing observation prior to first administration of the study drug. Subjects in the mITT population were analysed for this end point.

The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. CDAI response is defined by either a CDAI score of \< 150 or a CDAI reduction from baseline of at least 100 points, where baseline was the latest non-missing observation prior to first administration of the study drug. Subjects in the mITT population were analysed for this end point.

The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. The CDAI score of \< 150 represent CDAI remission. Subjects in the mITT population were analysed for this end point.

The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. CDAI 100-point improvement is defined as a reduction from baseline in CDAI score of at least 100 points/scores, where baseline was the latest nonmissing observation prior to first administration of the study drug. Subjects in the mITT population were analysed for this end point.

The CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days and includes subject reported symptoms, physician-assessed signs, and laboratory markers. The CDAI score is calculated by summing weighted scores for subjective items (number of liquid or very soft stools, the degree of abdominal pain over a week and general well-being; and objective items (associated signs, use of anti-diarrhoeal medication, abdominal mass, haematocrit, daily morning temperature, and body weight). The CDAI scores range approximately from 0 to 600, with higher scores indicating greater disease activity. Subjects in the mITT population were analysed for this end point.

An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, lifethreatening, a congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment (approximately 48 weeks). The safety population was analysed for this end point, which included all subjects who received any amount of study drug.

An AE is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A SAE is any AE that resulted in death,inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, lifethreatening, a congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment (approximately 148 weeks). Open-label population was analysed for this endpoint, which included all subjects who were enrolled in the 100-week, open-label treatment period and have at least one dose of open-label MEDI2070 210 mg SC treatment.

The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment (up to approximately 48 weeks). Subjects in the safety population were analysed for this end point.

The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1)to 36 weeks post treatment (up toapproximately 148 weeks). Open-label population was analysed for this endpoint, which included all subjects who were enrolled in the 100-week, open-label treatment period and have at least one dose of open-label MEDI2070 210 mg SC treatment.

The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1)to 36 weeks post treatment(approximately 48 weeks). Subjects in the safety population were analysed for this end point.

The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug (Day 1) to 36 weeks post treatment(approximately 148 weeks). Open-label population was analysed for this endpoint, which included all subjects who were enrolled in the 100-week, open-label treatment period and have at least one dose of open-label MEDI2070 210 mg SC treatment.

Pharmacokinetic (PK) population included all subjects who received at least one dose of MEDI2070(either in double-blind period or in open-label period) and had at least one PK sample that was above the lower limit of quantification was considered for this end point. Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for this time frames and is reported by an arbitrary value (NA).

The PK population included all subjects who received at least one dose of MEDI2070 (either in double-blind period or in open-label period) and had at least one PK sample that was above the lower limit of quantification was considered for this end point. Serum concentration of MEDI2070 for subject in 'Placebo' arm is not applicable for pre-dose Week 12 time frame and is reported by an arbitrary value (NA).

The PK population included all subjects who received at least one dose of MEDI2070 (either in double-blind period or in open-label period) and had at least one PK sample that was above the lower limit of quantification was considered for this end point.

MedImmune Ltd

Participants received IV placebo concentrate and solvent for injection/infusion at week 0 and week 4.

Participants received IV MEDI2070 700mg concentrate and solvent for injection/infusion at week 0 and week 4.

Experimental: MEDI2070 700mg

Participants randomized to placebo arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution injection/infusion every 4 week (Q4W) during the 100-week, open-label treatment period.

Placebo/MEDI2070 210mg

Subjects randomized to MEDI2070 700mg arm in double-blind period received 210 mg SC MEDI2070 concentrate and solvent for solution for injection/infusion Q4W during the 100-week, open-label treatment period.

MEDI2070 700mg/MEDI2070 210mg

A formal statistical analysis was not performed.

Value of 0 represents the open-label portion of the trial

Percentage of Participants With CDAI-70 Point Improvement at Week 8

Percentage of Participants With CDAI Response at Week 12

Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response at Week 8

Percentage of Participants With CDAI Remission at Week 8

Percentage of Participants With CDAI-100 Point Improvement at Week 8

Change From Baseline in CDAI Total Score at Week 8

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Double-blind Period

Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) in Double-blind Period

Value of 0 represents the double-blind portion of the trial

Number of Participants With TEAEs in Open-label Period

Number of Participants With TESAEs in Open-label Period

Anaemia

Leukopenia

Neutropenia

Urine analysis Abnormal

Urine Abnormality

Urine bilirubin increased

Proteinuria

Number of Participants With Clinical Laboratory Abnormalities as TEAEs in Double-blind Period

Lymphocyte

Lymphopenia

Neutrophil count increased

Platelet count increased

Red cell distribution width increased

White blood cell count decreased

Chromaturia

Blood uric acid increased

Hypokalaemia

Hepatic enzyme increased

Hyperlipidemia

Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs in Open-label Period

Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Double-blind Period

Number of Participants With Vital Signs Abnormalities Reported as TEAEs in Open-label Period

Week 0 Post-dose (60, 58)

Week 4 Pre-dose (54, 53)

Week 4 Post-dose (52, 51)

Week 8 Pre-dose (55, 51)

Serum MEDI2070 concentration data was summarized descriptively by visit. Value of 0 represents the open-label portion of the trial.

Maximum Mean Serum Concentration of MEDI2070 in Doubleblind Period

Week 12 Pre-dose (51, 52)

Week 24 Pre-dose (48, 43)

Week 112 Pre-dose (24, 20)

Serum MEDI2070 concentration data was summarized descriptively by visit. Value of 0 represents the double-blind portion of the trial.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Evaluation of Efficacy and Safety of Brazikumab (MEDI2070) in Participants With Active, Moderate to Severe Crohn's Disease	NCT02574637	Crohn's Disease	Brazikumab IV I... Brazikumab SC I... Placebo	18 Years - 80 Years	AstraZeneca
Evaluation of Efficacy and Safety of MEDI2070 in Patients With Active, Moderate-to-severe Crohn's Disease.	NCT01714726	Crohn's Disease	MEDI2070 placebo	18 Years - 65 Years	AstraZeneca

Spots Global Cancer Trial Database for moderate to severe crohn's disease