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A Study of Benralizumab in Patients With Eosinophilic Esophagitis (MESSINA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04543409
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis Biological: Benralizumab Biological: Matching placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Investigate the Use of Benralizumab for Eosinophilic Esophagitis
Actual Study Start Date : September 22, 2020
Estimated Primary Completion Date : March 8, 2022
Estimated Study Completion Date : November 14, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Benralizumab
Benralizumab active solution will be administered SC to patients by healthcare professionals in this clinical study using an accessorized prefilled syringe (APFS)
Biological: Benralizumab
Solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume

Placebo Comparator: Placebo
Placebo solution will be administered SC to patients by healthcare professionals in this clinical study using an accessorized prefilled syringe (APFS)
Biological: Matching placebo
Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC), 1 mL fill volume




Primary Outcome Measures :
  1. Proportion of patients with a histologic response at Week 24, defined as a peak esophageal intraepithelial eosinophil count ≤ 6 eos/hpf. [ Time Frame: Week 24 ]
  2. Changes from baseline in Dysphagia Symptom Questionnaire (DSQ) [ Time Frame: Week 24 ]
    The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia.


Secondary Outcome Measures :
  1. Changes from baseline in Endoscopic Reference Score (EREFS) [ Time Frame: Week 24 ]
    EREFS is a scoring system for assessing the presence and severity of the major endoscopic signs of EoE.The score ranges from 0 (normal) to 9 (severe disease).

  2. Esophageal histopathology findings [ Time Frame: Week 24 ]
    Histopathology findings analyzed by Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS). EoE-HSS assesses the severity (grade) and extent (stage) of abnormalities using a 4-point scale (0 normal; 3 maximum change)

  3. Dysphagia-free days [ Time Frame: Week 24 ]
    Dysphagia free days is a count ranging from 0-28. Higher counts indicate better outcomes.

  4. Frequency of dysphagia episodes as captured by the Eosinophilic Esophagitis Daily Dysphagia Diary (EoE-3D) [ Time Frame: Week 24 ]
    EoE-3D is a daily diary focused on the patient experience of EoE. The dysphagia-associated pain, discomfort, and overall severity scores range from 0 to 10, with higher scores meaning worse outcomes.

  5. Changes from baseline in dysphagia associated pain, discomfort, and overall severity as captured by the EoE-3D [ Time Frame: Week 24 ]
  6. Changes from baseline in abdominal pain and nausea as captured by the daily diary. [ Time Frame: Week 24 ]
  7. Changes from baseline in Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EOE-QoL-A) [ Time Frame: Week 24 ]
    The Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QoL-A) is a 30-item assessment developed specifically to measure health-related quality of life in patients with EoE. The overall score ranges from 0 to 96, with higher scores meaning better quality of life.

  8. Change from baseline in Short Form 36-item health survey (version 2, acute recall) (SF-36v2) [ Time Frame: Week 24 ]
    The Short Form 36-item Health Survey, version 2, acute recall (SF-36v2) is a 36-item, self-report survey of functional health and well-being, with a 1-week recall period. There are 8 domain scores: Physical Functioning (PF), Role Limitations due to Physical Health (RP), Bodily Pain (BP), General Health Perceptions (GH), Vitality (VT), Social Functioning (SF), Role Limitations due to Emotional Problems (RE), and Mental Health (MH). All scores range from 0-100, with higher scores meaning better outcomes.

  9. Healthcare resource utilization [ Time Frame: Week 24 ]
    Percent of patients with relevant concomitant procedures and healthcare resource utilization during the study through Week 24.

  10. Patient reported overall severity of disease as measured by Patient Global Impression of Severity (PGI-S) [ Time Frame: Week 24 ]
    Patient Global Impression of Severity (PGI-S) is an assessment of the patient's perceived disease severity. The answer options are "no symptoms," "very mild," "mild," "moderate," "severe," and "very severe."

  11. Patient reported change in health status since baseline as measured by Patient Global Impression of Change (PGI-C) [ Time Frame: Week 24 ]
    Patient Global Impression of Change (PGI-C) measures the patient's overall impression of response to treatment since the initial dose. The answer options are "much better," "moderately better," "a little better," "about the same/no change," "a little worse," "moderately worse," and "much worse."


Other Outcome Measures:
  1. Benralizumab Pharmacokinetics [ Time Frame: Minimum of 52 weeks ]
    Serum concentrations of benralizumab.

  2. Immunogenicity of benralizumab [ Time Frame: Minimum of 52 weeks ]
    Immunogenicity of benralizumab assessed by ADA and nAb.

  3. Safety and tolerability [ Time Frame: Minimum of 52 weeks ]
    - Percentage of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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). A patient reported average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to the Visit 1
  • 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.
  • 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 16 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.
  • Use of a feeding tube, or 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04543409


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Marc E. Rothenberg, MD, PhD Children's Hospital Medical Center, Cincinnati
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04543409    
Other Study ID Numbers: D3255C00001
2019-002871-32 ( EudraCT Number )
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Eosinophilic Esophagitis
EoE
Benralizumab
Additional relevant MeSH terms:
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Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents