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

• ClinicalTrials.gov Identifier: NCT02574637
• Recruitment Status: Terminated
• First Posted: October 14, 2015
• Results First Posted: May 15, 2020
• Last Update Posted: May 15, 2020
• Sponsor: Allergan
• Information provided by (Responsible Party): Allergan

Tracking Information

• First Submitted Date: September 24, 2015
• First Posted Date: October 14, 2015
• Results First Submitted Date: May 1, 2020
• Results First Posted Date: May 15, 2020
• Last Update Posted Date: May 15, 2020
• Actual Study Start Date: January 5, 2016
• Actual Primary Completion Date: July 28, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 14, 2020)

Percentage of Participants With Crohn's Disease Activity Index (CDAI) Remission at Week 8 [ Time Frame: Week 8 ]

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.

• Original Primary Outcome Measures (submitted: October 9, 2015): The primary endpoint of the study is Crohn's Disease Activity Index (CDAI) clinical remission at Week 8, defined by a CDAI score of < 150 [ Time Frame: Week 8 ]

Current Secondary Outcome Measures (submitted: May 14, 2020)

• Percentage of Participants With Loose/Liquid Stool Frequency Response [ Time Frame: Baseline, Weeks 8, 16 and 28 ]
  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.
• Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response [ Time Frame: Baseline, Weeks 8, 16 and 28 ]
  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.
• Percentage of Participants With CDAI Clinical Remission [ Time Frame: Weeks 16 and 28 ]
  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.
• Percentage of Participants With Simple Endoscopic Score for Crohn's Disease (SES-CD) Response [ Time Frame: Baseline, Weeks 16 and 28 ]
  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.
• Percentage of Participants With Loose/Liquid Stool Frequency Remission [ Time Frame: Baseline, Weeks 8, 16 and 28 ]
  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.
• Percentage of Participants With Simple Endoscopic Score for Crohn's Disease (SES-CD) Remission [ Time Frame: Weeks 16 and 28 ]
  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.
• Percentage of Participants With Patient Response Outcome-2 (PRO2) Remission [ Time Frame: Weeks 8, 16 and 28 ]
  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.
• Percentage of Participants With PRO2 Response [ Time Frame: Baseline, Weeks 8, 16 and 28 ]
  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.
• Serum Interleukin (IL)-22 and Serum Lipocalin 2 (LCN2) Concentration as a Biomarker of Brazikumab's Efficacy [ Time Frame: Weeks 16 and 28 ]
• Percentage of Participants With CDAI Modified Sustained Clinical Remission at Both Weeks 8 and 28 [ Time Frame: Weeks 8 and 28 ]
  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.
• Serum Brazikumab Concentration [ Time Frame: Predose at Weeks 0, 1, 4, 8, 12, 16, 28; Postdose at Weeks 0 and 4 ]
• Number of Participants With Serum Anti-drug Antibodies for Brazikumab [ Time Frame: Predose at Weeks 0, 4, 12, 16, 28, 40 and 52 ]
• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), TEAEs of Special Interest and TEAEs Leading to Discontinuation [ Time Frame: From first dose of study drug up to 28 weeks post last dose (approximately up to Week 80) ]
  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.
• Number of Participants With Clinically Significant Laboratory Values [ Time Frame: From first dose of study drug up to 28 weeks post last dose (approximately up to Week 80) ]
  Laboratory parameters included tests for hematology, serum chemistry and urinalysis. Laboratory values that were outside the reference range, considered clinically significant were reported.
• Percentage of Participants With Abdominal Pain Response [ Time Frame: Baseline; Weeks 8, 16 and 28 ]
  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.
• Percentage of Participants With Abdominal Pain Remission [ Time Frame: Weeks 8, 16 and 28 ]
  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.

Original Secondary Outcome Measures (submitted: October 9, 2015)

• A decrease in stool frequency from baseline at Week 8, Week 16 and Week 28 [ Time Frame: Week 8, Week 16 and Week 28 ]
• A reduction of at least 100 points from baseline in Crohn's Disease Activity Index (CDAI) at Week 8, Week 16 and Week 28 [ Time Frame: Week 8, Week 16 and Week 28 ]
• Crohn's Disease Activity Index (CDAI) clinical remission at Week 16 and Week 28 [ Time Frame: Week 16 and Week 28 ]
• Simple Endoscopic Score for Crohn's Disease (SES-CD) improvement in gut mucosa at Week 16 and Week 28 [ Time Frame: Week 16 and Week 28 ]
• Sustained decrease in stool frequency from baseline at Week 8 and Week 28 [ Time Frame: Week 8 and Week 28 ]
• Crohn's Disease Activity Index (CDAI) Modified sustained clinical remission at Week 8 and Week 28 [ Time Frame: Week 8 and Week 28 ]
• Simple Endoscopic Score for Crohn's Disease (SES-CD) sustained improvement in gut mucosa at Week 16 and Week 28 [ Time Frame: Week 16 and Week 28 ]
• Correlate biomarkers with clinical outcomes at Week 8 [ Time Frame: Week 8 ]
• Serum concentration evaluation of MEDI2070 levels [ Time Frame: Weeks 1-28 ]
• Number of incidences of Anti-drug antibodies (ADA) against MEDI2070 [ Time Frame: Weeks 4-52 ]
• Number of incidences of treatment-emergent adverse events [ Time Frame: Weeks 0-80 ]
• Number of incidences of treatment-emergent serious adverse events [ Time Frame: Weeks 0-80 ]
• Number of incidences of treatment-emergent adverse events of special interest [ Time Frame: Weeks 0-80 ]
• Number of incidences of adverse events leading to investigational product discontinuation [ Time Frame: Weeks 0-48 ]
• Number of incidences of specific laboratory abnormalities [ Time Frame: Weeks 0-80 ]
• A decrease in abdominal pain from baseline at Week 8, Week 16 and Week 28 [ Time Frame: Week 8, Week 16 and Week 28 ]
• Sustained decrease abdominal pain from baseline at Week 8 and Week 28 [ Time Frame: Week 8 and Week 28 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Efficacy and Safety of Brazikumab (MEDI2070) in Participants With Active, Moderate to Severe Crohn's Disease
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Drug: Brazikumab IV Infusion
  Brazikumab IV infusion as per protocol specified dosing schedule.
  Other Name: MEDI2070
• Drug: Brazikumab SC Injection
  Brazikumab IV infusion as per protocol specified dosing schedule.
  Other Name: MEDI2070
• Drug: Placebo
  Placebo-matching Brazikumab IV infusion as per protocol specified dosing schedule.

Study Arms

• Placebo Comparator: Placebo
  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.
  Interventions:

  • Drug: Brazikumab IV Infusion
  • Drug: Brazikumab SC Injection
  • Drug: Placebo
• Experimental: Brazikumab High Dose
  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.
  Interventions:

  • Drug: Brazikumab IV Infusion
  • Drug: Brazikumab SC Injection
  • Drug: Placebo
• Experimental: Brazikumab High-Medium 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 in the maintenance phase and open-label period up to Week 48.
  Interventions:

  • Drug: Brazikumab IV Infusion
  • Drug: Brazikumab SC Injection
  • Drug: Placebo
• Experimental: Brazikumab Low-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. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.
  Interventions:

  • Drug: Brazikumab IV Infusion
  • Drug: Brazikumab SC Injection
  • Drug: Placebo
• Experimental: Brazikumab Low 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. Participants received brazikumab 210 mg, SC injection, every 4 weeks up to Week 48 in the open-label period.
  Interventions:

  • Drug: Brazikumab IV Infusion
  • Drug: Brazikumab SC Injection
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 28, 2017): 29
• Original Estimated Enrollment (submitted: October 9, 2015): 342
• Actual Study Completion Date: January 29, 2018
• Actual Primary Completion Date: July 28, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of ileal, ileo-colonic, or colonic Crohn's Disease (CD) for > 3 months prior to screening
• Men or women age 18 - 80 years at the time of screening
• Moderate to severely active CD, as defined by Crohn's Disease Activity Index (CDAI) and endoscopic demonstration of inflammation
• Stable dose of medications for Crohn's disease therapy
• Prior treatment failure or intolerance with at least one Anti-Tumor Necrosis Factor-Alpha Therapy (anti-TNF α) agent
• Effective contraception from screening, and for 36 weeks after the last dose of investigational product
• No known history of active tuberculosis (TB) & negative assessment for TB/latent TB

Exclusion Criteria:

• Severe underlying immunosuppression
• Severe gastrointestinal complications; e.g., short bowel syndromes, obstructing strictures, recent or planned bowel surgery, Ileostomy and/or colostomy, recent bowel perforation
• Significant infections at screening; Infected abscess, positive for Clostridium difficile, recent infectious hospitalization
• Recent treatment with approved or investigational biologic therapy for Crohn's disease
• Recent or planned live attenuated vaccine
• History of cancer, except for basal cell carcinoma or carcinoma in situ (CIS) of the cervix with apparent cure ≥ 12 months before screening
• Pregnancy/breast feeding
• Drug abuse

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy, Australia, Belgium, Canada, France, Germany, Hungary, Israel, Netherlands, Russian Federation, Spain, United States
• Removed Location Countries: Bulgaria, Czech Republic, Korea, Republic of, Poland, Turkey, United Kingdom

Administrative Information

• NCT Number: NCT02574637
• Other Study ID Numbers: D5170C00002; 2015-000609-38 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Allergan
• Study Sponsor: Allergan
• Collaborators: Not Provided

Investigators

• Study Director: Carl Gommoll, MS; Allergan

• PRS Account: Allergan
• Verification Date: May 2020