Clinical trial NCT04543409: A Study of Benralizumab in Patients With Eosinophilic Esophagitis
Official title: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Eosinophilic Esophagitis
Keywords: Eosinophilic Esophagitis
EoE
Benralizumab
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-09-10
Enrollment: 211
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this Phase 3 study is to investigate the use of benralizumab as a treatment for patients with EoE. The effect of doses of benralizumab on EoE histologic signs and symptoms will be assessed over a 52-week treatment period (including a 24-week double-blind placebo-controlled treatment period and a 28-week open-label treatment period). It is proposed that benralizumab will deplete eosinophils from GI tissue(s), improve the symptoms of dysphagia, and improve endoscopy scores as well as other markers of disease activity. Upon completion of the initial 52-week treatment period, patients will be offered an additional Open Label Extension period of at least 1 year, with benralizumab treatment and ongoing study assessments.


Eligibility criteria: Inclusion Criteria:

* Patients 12 to 65 years of age, inclusive, at the time of signing the informed consent or assent (if applicable) form.
* Documented previous diagnosis of EoE by endoscopy.
* Must be symptomatic at Visit 1 (screening) and Visit 2 (randomization):

  1. A patient reported an average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to Visit 1 AND
  2. An average of at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) between Visit 1 and Visit 2, and at least 2 days per week with an episode of dysphagia (Daily DSQ ≥2) in each of the 2 weeks immediately prior to randomization
* May be on background medications for EoE and related treatments during the study as long as the background medications have been stable for at least 4 weeks (8 weeks for PPI) prior to the screening and there is agreement not to change type of background medication or dosage during the run-in period and for the first 52 weeks of the study unless a change is medically indicated.
* Negative serum pregnancy test for female patients of childbearing potential at Visit1.
* Women of childbearing potential must agree to use a highly effective form of birth control (confirmed by the Investigator) from randomization throughout the study duration and within 12 weeks after last dose if IP.

Exclusion Criteria:

* Other GI disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease.
* Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation during the run-in period.
* Esophageal dilation performed within 8 weeks prior to screening and prior esophageal surgery that would impact the assessments for EoE
* Use of a feeding tube, or having a pattern of not eating solid food daily during the run-in period.
* Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood eosinophil count \>1500 eos/μL.
* EGPA vasculitis.
* Eosinophilic gastritis, gastroenteritis, enteritis, or colitis documented by biopsy.
* Current malignancy, or history of malignancy with some specific exceptions.
* History of anaphylaxis to any biologic therapy or vaccine.
* Current active liver disease:

  * Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen \[HBsAg\] or hepatitis C antibody), or other stable chronic liver disease are acceptable if patient otherwise meets eligibility criteria.
  * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN), confirmed by repeated testing during the run-in period.
* Helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent or assent (if applicable) is obtained that has not been treated with or has failed to respond to standard of care therapy.
* History of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
* Concomitant use of immunosuppressive medication.
* Initiation or change of a food-elimination diet regimen or reintroduction of a previously eliminated food group in the 6 weeks prior to start of the run-in period.
* Currently pregnant, breastfeeding, or lactating women.

Primary outcomes:
measure: Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.
timeFrame: Week 24, Week 52
measure: Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)
timeFrame: Week 24, Week 52
Secondary outcomes:
measure: Percent Change From Baseline in Tissue Eosinophils
timeFrame: Week 24, Week 52
measure: Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24
timeFrame: Week 24
measure: Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24
timeFrame: Week 24
measure: Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)
timeFrame: Week 24, Week 52
measure: Treatment Responder Rate at Week 24, Defined as a Composite of Histological Response (≤6eos/Hpf) and Clinically Meaningful Improvement From Baseline in Dysphagia Symptom Questionnaire (DSQ) (30% Improvement) at Week 24
timeFrame: Week 24
measure: Centrally-read Biopsies for Additional Histopathology Including Tissue Eosinophil Counts at Week 24
timeFrame: Week 24
measure: Dysphagia-free Days as Captured by the Dysphagia Symptom Questionnaire (DSQ)
timeFrame: Week 24, Week 52
measure: Frequency of Dysphagia Episodes as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D)
timeFrame: Week 24, Week 52
measure: Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 24
timeFrame: Week 24
measure: Changes From Baseline in Dysphagia Associated Pain, Discomfort, and Overall Severity as Captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) at Week 52
timeFrame: Week 52
measure: Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 24
timeFrame: Week 24
measure: Changes From Baseline in Abdominal Pain and Nausea as Captured by the Daily Diary at Week 52
timeFrame: Week 52
measure: Changes From Baseline in the Pediatric Eosinophilic Esophagitis Symptom Severity Module (PEESS)
timeFrame: Week 24, Week 52
measure: Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 24
timeFrame: Week 24
measure: Changes From Baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) at Week 52
timeFrame: Week 52
measure: Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 24
timeFrame: Week 24
measure: Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) at Week 52
timeFrame: Week 52
measure: Percent of Patients With Relevant Concomitant Procedures and Healthcare Resource Utilization at Week 24 and Week 52.
timeFrame: Week 24, Week 52
measure: Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 24
timeFrame: Week 24
measure: Patient Reported Overall Severity of Disease as Measured by Patient Global Impression of Severity (PGI-S) at Week 52
timeFrame: Week 52
measure: Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 24
timeFrame: Week 24
measure: Patient Reported Change in Health Status Since Baseline as Measured by Patient Global Impression of Change (PGI-C) at Week 52
timeFrame: Week 52
Other outcomes:
measure: Benralizumab Pharmacokinetics
timeFrame: Up to week 52
measure: Immunogenicity of Benralizumab in Double Blind Period
timeFrame: Up to Week 24
measure: Immunogenicity of Benralizumab in Double Blind + Open Label Periods
timeFrame: Up to Week 52
measure: Safety and Tolerability in Double Blind Period
timeFrame: Up to Week 24
measure: Safety and Tolerability in the Open Label Period
timeFrame: From Week 24 up to Week 52
Locations:
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
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state: Georgia
city: Chicago
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state: Illinois
city: Normal
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state: Illinois
city: Park Ridge
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state: Illinois
city: White Marsh
country: United States
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state: Maryland
city: Boston
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state: Massachusetts
city: Boston
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state: Massachusetts
city: Chesterfield
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state: Michigan
city: Rochester
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state: Minnesota
city: Lincoln
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state: Nebraska
city: Ocean City
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state: New Jersey
city: New York
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state: New York
city: Chapel Hill
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state: North Carolina
city: Winston-Salem
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state: North Carolina
city: Cincinnati
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state: Ohio
city: Philadelphia
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state: Pennsylvania
city: Uniontown
country: United States
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state: Pennsylvania
city: Salt Lake City
country: United States
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state: Utah
city: Salt Lake City
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state: Utah
city: Richmond
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state: Virginia
city: Hamilton
country: Canada
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state: Ontario
city: London
country: Canada
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state: Ontario
city: Ottawa
country: Canada
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state: Ontario
city: Windsor
country: Canada
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state: Ontario
city: Dijon Cedex
country: France
facility: Research Site
city: Lille Cedex
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Lyon Cedex 03
country: France
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city: Pessac
country: France
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city: Suresnes Cedex
country: France
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city: Toulouse Cedex 9
country: France
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city: Frankfurt
country: Germany
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city: München
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Remscheid
country: Germany
facility: Research Site
city: Afula
country: Israel
facility: Research Site
city: Holon
country: Israel
facility: Research Site
city: Kfar-Saba
country: Israel
facility: Research Site
city: Petach-Tikva
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Rozzano
country: Italy
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city: Verona
country: Italy
facility: Research Site
city: Chiba-Shi
country: Japan
facility: Research Site
city: Izumo-shi
country: Japan
facility: Research Site
city: Maebashi-shi
country: Japan
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city: Osaka-shi
country: Japan
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city: Amsterdam
country: Netherlands
facility: Research Site
city: Nieuwegein
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
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city: Gdańsk
country: Poland
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city: Knurów
country: Poland
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city: Lublin
country: Poland
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city: Rzeszow
country: Poland
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city: Szczecin
country: Poland
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city: Warszawa
country: Poland
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city: Wrocław
country: Poland
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city: Łódź
country: Poland
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city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
facility: Research Site
city: Badalona
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
facility: Research Site
city: Bilbao
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
facility: Research Site
city: Brighton
country: United Kingdom
facility: Research Site
city: Darlington
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Marc E. Rothenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: