Clinical trial NCT02574637: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Crohn's Disease
Keywords: MEDI2070
inflammatory bowel disease
moderate to severe Crohn's Disease
IL-23
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-10-14
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Remission at Week 8
timeFrame: Week 8
Secondary outcomes:
measure: Percentage of Participants With Loose/Liquid Stool Frequency Response
timeFrame: Baseline, Weeks 8, 16 and 28
measure: Percentage of Participants With Crohn's Disease Activity Index (CDAI) Response
timeFrame: Baseline, Weeks 8, 16 and 28
measure: Percentage of Participants With CDAI Clinical Remission
timeFrame: Weeks 16 and 28
measure: Percentage of Participants With Simple Endoscopic Score for Crohn's Disease (SES-CD) Response
timeFrame: Baseline, Weeks 16 and 28
measure: Percentage of Participants With Loose/Liquid Stool Frequency Remission
timeFrame: Baseline, Weeks 8, 16 and 28
measure: Percentage of Participants With Simple Endoscopic Score for Crohn's Disease (SES-CD) Remission
timeFrame: Weeks 16 and 28
measure: Percentage of Participants With Patient Response Outcome-2 (PRO2) Remission
timeFrame: Weeks 8, 16 and 28
measure: Percentage of Participants With PRO2 Response
timeFrame: Baseline, Weeks 8, 16 and 28
measure: Serum Interleukin (IL)-22 and Serum Lipocalin 2 (LCN2) Concentration as a Biomarker of Brazikumab's Efficacy
timeFrame: Weeks 16 and 28
measure: Percentage of Participants With CDAI Modified Sustained Clinical Remission at Both Weeks 8 and 28
timeFrame: Weeks 8 and 28
measure: Serum Brazikumab Concentration
timeFrame: Predose at Weeks 0, 1, 4, 8, 12, 16, 28; Postdose at Weeks 0 and 4
measure: Number of Participants With Serum Anti-drug Antibodies for Brazikumab
timeFrame: Predose at Weeks 0, 4, 12, 16, 28, 40 and 52
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), TEAEs of Special Interest and TEAEs Leading to Discontinuation
timeFrame: From first dose of study drug up to 28 weeks post last dose (approximately up to Week 80)
measure: Number of Participants With Clinically Significant Laboratory Values
timeFrame: From first dose of study drug up to 28 weeks post last dose (approximately up to Week 80)
measure: Percentage of Participants With Abdominal Pain Response
timeFrame: Baseline; Weeks 8, 16 and 28
measure: Percentage of Participants With Abdominal Pain Remission
timeFrame: Weeks 8, 16 and 28
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Research, PLLC
state: Arizona
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: Lone Tree
country: United States
facility: South Denver Gastroenterology, PC
state: Colorado
city: Lone Tree
country: United States
facility: Research Site
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research of West Florida - Corporate
state: Florida
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Advanced Pharma CR, LLC
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC, Inc.
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Evanston
country: United States
facility: Research Site
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center, Digestive Health
state: Kansas
city: Topeka
country: United States
facility: Research Site
state: Kansas
city: Bowling Green
country: United States
facility: Graves Gilbert Clinic
state: Kentucky
city: Bowling Green
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Lake Charles
country: United States
facility: Clinical Trials of SW Louisiana, LLC
state: Louisiana
city: Lake Charles
country: United States
facility: Research Site
state: Louisiana
city: Metairie
country: United States
facility: Clinical Trials Management, LLC
state: Louisiana
city: Metairie
country: United States
facility: Research Site
state: Louisiana
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Southfield
country: United States
facility: Research Site
state: Michigan
city: Southfield
country: United States
facility: Revival Research Institute, LLC
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Belton
country: United States
facility: Ehrhardt Clinical Research, LLC
state: Missouri
city: Belton
country: United States
facility: Research Site
state: Missouri
city: Great Neck
country: United States
facility: New York University Medical Center
state: New York
city: Poughkeepsie
country: United States
facility: Premier Medical Group of the Hudson Valley, PC
state: New York
city: Poughkeepsie
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Dayton
country: United States
facility: Clinical Inquest Center Ltd
state: Ohio
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Sayre
country: United States
facility: Donald Guthrie Foundation
state: Pennsylvania
city: Sayre
country: United States
facility: Research Site
state: Pennsylvania
city: Chattanooga
country: United States
facility: Erlanger Health System
state: Tennessee
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: Gastroenterology Research of America
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Temple
country: United States
facility: Baylor Research Institute
state: Texas
city: Temple
country: United States
facility: Research Site
state: Texas
city: Milwaukee
country: United States
facility: Allegiance Research Specialists, LLC
state: Wisconsin
city: Wauwatosa
country: United States
facility: Research Site
state: Wisconsin
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Research Site
city: Bonheiden
country: Belgium
facility: Imeldaziekenhuis
city: Bonheiden
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: UZ Leuven
city: London
country: Canada
facility: London Health Science Centre
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: LHSC - Victoria Hospital
state: Ontario
city: Saskatoon
country: Canada
facility: Research Site
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Toulouse Cedex 09
country: France
facility: CHU de Toulouse - Hôpital Rangueil
state: Haute Garonne
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hôpital Pontchaillou
state: Ille Et Vilaine
city: Saint Etienne
country: France
facility: CHU Saint Etienne - Hôpital Nord
state: Loire
city: Vandoeuvre les Nancy
country: France
facility: Hôpital de Brabois Adultes
state: Meurthe Et Moselle
city: Rennes
country: France
facility: Research Site
city: Saint-Priez En Jarez
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Vandoeuvre-Les-Nancy
country: France
facility: Research Site
city: Marburg
country: Germany
facility: Medizinische Hochschule Hannover
state: Hessen
city: Dortmund
country: Germany
facility: St. Johannes Hospital
state: Nordrhein Westfalen
city: Dortmund
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Magyar Honvedseg Egeszsegugyi Kozpont
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak
city: Rechovot
country: Israel
facility: Kaplan Medical Center
city: Rehovot
country: Israel
facility: Research Site
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
city: Rozzano
country: Italy
facility: Research Site
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Maastricht
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Research Site
city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Krasnoyarsk
country: Russian Federation
facility: TSBIH "Territorial Clinical Hospital"
city: Saint-Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
Study officials:
References: