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

Crohn's Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02574637
• Other study ID #: D5170C00002
• Secondary ID: 2015-000609-38
• Status: Terminated
• Phase: Phase 2
• Start date: January 5, 2016
• Est. completion date: January 29, 2018

Study information

• Verified date: May 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: January 29, 2018
• Est. primary completion date: July 28, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 a) 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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

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

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Australia	Research Site	Woolloongabba
Belgium	Imeldaziekenhuis	Bonheiden
Belgium	Research Site	Bonheiden
Belgium	Research Site	Leuven
Belgium	UZ Leuven	Leuven
Canada	LHSC - Victoria Hospital	London	Ontario
Canada	London Health Science Centre	London	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Royal University Hospital	Saskatoon	Saskatchewan
France	Research Site	Rennes
France	CHU Rennes - Hôpital Pontchaillou	Rennes cedex 09	Ille Et Vilaine
France	CHU Saint Etienne - Hôpital Nord	Saint Etienne	Loire
France	Research Site	Saint-Priez En Jarez
France	CHU de Toulouse - Hôpital Rangueil	Toulouse Cedex 09	Haute Garonne
France	Research Site	Toulouse Cedex 9
France	Hôpital de Brabois Adultes	Vandoeuvre les Nancy	Meurthe Et Moselle
France	Research Site	Vandoeuvre-Les-Nancy
Germany	Research Site	Dortmund
Germany	St. Johannes Hospital	Dortmund	Nordrhein Westfalen
Germany	Research Site	Hannover
Germany	Medizinische Hochschule Hannover	Marburg	Hessen
Hungary	Magyar Honvedseg Egeszsegugyi Kozpont	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak	Budapest
Israel	Kaplan Medical Center	Rechovot
Israel	Research Site	Rehovot
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Italy	Research Site	Rozzano
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Research Site	Maastricht
Netherlands	Erasmus Medisch Centrum	Rotterdam
Netherlands	Research Site	Rotterdam
Russian Federation	Research Site	Krasnoyarsk
Russian Federation	TSBIH "Territorial Clinical Hospital"	Krasnoyarsk
Russian Federation	Pavlov First Saint Petersburg State Medical University	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Research Site	Barcelona
Spain	Hospital Universitari de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat
United States	Research Site	Ann Arbor	Michigan
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Ehrhardt Clinical Research, LLC	Belton	Missouri
United States	Research Site	Belton	Missouri
United States	Graves Gilbert Clinic	Bowling Green	Kentucky
United States	Research Site	Bowling Green	Kentucky
United States	Research Site	Charlotte	North Carolina
United States	Erlanger Health System	Chattanooga	Tennessee
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Clinical Research of West Florida - Corporate	Clearwater	Florida
United States	Clinical Inquest Center Ltd	Dayton	Ohio
United States	Research Site	Dayton	Ohio
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	Research Site	Evanston	Illinois
United States	New York University Medical Center	Great Neck	New York
United States	Gastroenterology Research of America	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Research Site	Indianapolis	Indiana
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	Research Site	Jacksonville	Florida
United States	Clinical Trials of SW Louisiana, LLC	Lake Charles	Louisiana
United States	Research Site	Lake Charles	Louisiana
United States	Research Site	Lone Tree	Colorado
United States	South Denver Gastroenterology, PC	Lone Tree	Colorado
United States	Research Site	Louisville	Kentucky
United States	University of Louisville	Louisville	Kentucky
United States	Clinical Trials Management, LLC	Metairie	Louisiana
United States	Research Site	Metairie	Louisiana
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Research Site	Miami	Florida
United States	Allegiance Research Specialists, LLC	Milwaukee	Wisconsin
United States	IMIC, Inc.	Palmetto Bay	Florida
United States	Arizona Arthritis & Rheumatology Research, PLLC	Phoenix	Arizona
United States	Research Site	Phoenix	Arizona
United States	Premier Medical Group of the Hudson Valley, PC	Poughkeepsie	New York
United States	Research Site	Poughkeepsie	New York
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Research Site	Rochester	Minnesota
United States	Donald Guthrie Foundation	Sayre	Pennsylvania
United States	Research Site	Sayre	Pennsylvania
United States	Research Site	Southfield	Michigan
United States	Revival Research Institute, LLC	Southfield	Michigan
United States	Baylor Research Institute	Temple	Texas
United States	Research Site	Temple	Texas
United States	Cotton-O'Neil Clinical Research Center, Digestive Health	Topeka	Kansas
United States	Research Site	Topeka	Kansas
United States	Research Site	Wauwatosa	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Russian Federation,  Spain, 

Outcome

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