A Study of Benralizumab in Patients With Eosinophilic Esophagitis

NCT04543409 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: D3255C000012019-002871-32
• Study Type: interventional
• Target: 211
• Locations: 12 countries
• Sites: 78

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.

Conditions

Eosinophilic Esophagitis

Keywords

Eosinophilic Esophagitis; EoE; Benralizumab

Outcome Measures

Primary Outcomes (2)

• Percentage of Patients With a Histologic Response, Defined as a Peak Esophageal Intraepithelial Eosinophil Count ≤ 6 Eos/Hpf.

  Percentage of patients with a histologic response at Week 24 and Week 52. A histologic response is defined as a peak esophageal intraepithelial eosinophil count \<= 6 eos/hpf across all available esophageal levels. Subjects with no biopsy data at Week 24 or with intercurrent events prior to Week 24 such as changes to background medications or additional new therapies for EoE are considered non-responders. The number analyzed represents the number of participants in the treatment group that could have made it to the timepoint by the data cut off.

  Week 24, Week 52

• Changes From Baseline in Dysphagia Symptom Questionnaire (DSQ)

  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. At least 8 days with evaluable daily score in 14-day period are required; otherwise the DSQ score for the period is set to missing. The number analyzed represents the number of participants with data at that visit (including patients with imputed values post intercurrent events).

  Week 24, Week 52

Secondary Outcomes (22)

• Percent Change From Baseline in Tissue Eosinophils

  Week 24, Week 52

• Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Grade Score at Week 24

  Week 24

• Change From Baseline in Eosinophilic Esophagitis-Histology Scoring System (EoE-HSS) Total Stage Score at Week 24

  Week 24

• Changes From Baseline in Centrally-read Endoscopic Reference Score (EREFS)

  Week 24, Week 52

• 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

  Week 24

Other Outcomes (5)

• Benralizumab Pharmacokinetics

  Up to week 52

• Immunogenicity of Benralizumab in Double Blind Period

  Up to Week 24

• Immunogenicity of Benralizumab in Double Blind + Open Label Periods

  Up to Week 52

Study Arms (2)

Benralizumab

EXPERIMENTAL

Benralizumab active solution will be administered SC to patients by healthcare professionals in this clinical study using an accessorized prefilled syringe (APFS)

Biological: Benralizumab

Placebo

PLACEBO COMPARATOR

Placebo solution will be administered SC to patients by healthcare professionals in this clinical study using an accessorized prefilled syringe (APFS)

Biological: Matching placebo

Interventions

Benralizumab BIOLOGICAL

Solution for injection in a single accessorized prefilled syringe (APFS) will be administered subcutaneously (SC), 1 mL fill volume

Benralizumab

Matching placebo BIOLOGICAL

Matching placebo solution for injection in APFS, 1 mL fill volume. Placebo solution will be administered subcutaneously (SC), 1 mL fill volume

Placebo

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 an average of at least 2 days per week with an episode of dysphagia over the 4 weeks prior to Visit 1 AND
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (78)

Research Site

Little Rock, Arkansas, 72202, United States

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St. Petersburg, Florida, 33709, United States

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Atlanta, Georgia, 30322-1013, United States

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Chicago, Illinois, 60611, United States

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Normal, Illinois, 61761, United States

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Park Ridge, Illinois, 60068, United States

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White Marsh, Maryland, 21162, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02115, United States

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Chesterfield, Michigan, 48047, United States

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Rochester, Minnesota, 55905, United States

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Lincoln, Nebraska, 68510, United States

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Ocean City, New Jersey, 07712, United States

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New York, New York, 10029, United States

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Chapel Hill, North Carolina, 27514, United States

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Winston-Salem, North Carolina, 27157, United States

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Cincinnati, Ohio, 45229, United States

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Philadelphia, Pennsylvania, 19104, United States

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Uniontown, Pennsylvania, 15401, United States

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Salt Lake City, Utah, 84107, United States

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Salt Lake City, Utah, 84132, United States

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Richmond, Virginia, 23219, United States

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Hamilton, Ontario, L8S 1G5, Canada

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London, Ontario, N6A 5W9, Canada

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Ottawa, Ontario, K1H 1E4, Canada

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Windsor, Ontario, N8X 2G1, Canada

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Dijon, 21079, France

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Lille, 59037, France

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Lille, F-59037, France

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Lyon, 69437, France

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Pessac, 33600, France

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Suresnes, 92151, France

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Toulouse, 31059, France

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Frankfurt, 60590, Germany

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München, 80337, Germany

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München, 81675, Germany

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Remscheid, 42859, Germany

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Afula, 18341, Israel

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Holon, 58100, Israel

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Kfar Saba, 4428164, Israel

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Petah Tikva, 4920235, Israel

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Tel Aviv, 64239, Israel

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Florence, 50134, Italy

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Genova, 16126, Italy

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Napoli, 80131, Italy

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Pisa, 56124, Italy

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Rozzano, 20089, Italy

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Verona, 37134, Italy

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Chiba, 260-0877, Japan

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Izumo-shi, 693-8501, Japan

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Maebashi, 371-8511, Japan

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Osaka, 545-8586, Japan

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Amsterdam, 1105 AZ, Netherlands

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Nieuwegein, 3435 CM, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Gdansk, 80-214, Poland

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Knurów, 44-190, Poland

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Lodz, 93-338, Poland

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Lublin, 20-582, Poland

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Rzeszów, 35-302, Poland

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Szczecin, 71-434, Poland

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Warsaw, 04-141, Poland

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Wroclaw, 50-449, Poland

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Chelyabinsk, 454091, Russia

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Moscow, 105066, Russia

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Moscow, 111123, Russia

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Moscow, 119992, Russia

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Badalona, 08916, Spain

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Bilbao, 48013, Spain

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Madrid, 28006, Spain

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Madrid, 28031, Spain

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Madrid, 28040, Spain

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Brighton, BN2 5BE, United Kingdom

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Darlington, DL3 6HX, United Kingdom

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London, E1 2AJ, United Kingdom

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London, SW17 0RE, United Kingdom

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Related Publications (1)

• Rothenberg ME, Dellon ES, Collins MH, Bredenoord AJ, Hirano I, Peterson KA, Brooks L, Caldwell JM, Fjallbrant H, Grindebacke H, Ho CN, Keith M, McCrae C, Sinibaldi D, White WI, Datto CJ; MESSINA Trial Investigators. Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis. N Engl J Med. 2024 Jun 27;390(24):2252-2263. doi: 10.1056/NEJMoa2313318.

  PMID: 38924732 DERIVED

Related Links

• This is a poster.
• CSR Synopsis
• Redacted CSP
• Redacted SAP

MeSH Terms

Conditions

Eosinophilic Esophagitis

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Marc E. Rothenberg, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: September 10, 2020
• Study Start: September 22, 2020
• Primary Completion: September 19, 2022
• Study Completion: February 6, 2023
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

GB (4); CA (4); NL (3); IT (6); DE (4); IL (5); RU (4); FR (7); JP (4); US (22); PL (8); ES (7)