Efficacy and Safety of Benralizumab in Patients With Eosinophilic Gastritis and/or Gastroenteritis (The HUDSON GI Study) (HUDSON GI)

A Multi-center, Randomized, Double-blind, Parallel-group, Placebo-controlled 3-Part Phase 3 Study to Demonstrate the Efficacy and Safety of Benralizumab in Patients With Eosinophilic Gastritis and/or Gastroenteritis (The HUDSON GI Study)

This is a 3-part study. Part A is randomized, double-blinded, placebo-controlled and includes patients with eosinophilic gastritis and/or duodenal-only disease. After completing Part A, participants can continue to Part C - open-label benralizumab treatment period. Following the decision to close enrollment, patients in both Part A and Part C will be given the option to proceed to 6-months of open-label benralizumab treatment in Part D.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Gastritis; Eosinophilic Gastroenteritis
• Intervention / Treatment: Biological: Benralizumab; Biological: Placebo

Detailed Description

The aim of this Phase 3 study is to investigate the use of benralizumab as a treatment for patients with Eosinophilic Gastritis and/or Gastroenteritis. The effect of doses of benralizumab on EG/EGE histologic signs and symptoms will be assessed in a 24-week double-blind placebo-controlled treatment period followed by assessments during an open-label benralizumab treatment period. It is proposed that benralizumab will deplete eosinophilis, improve the symptoms in patients with eosinophilic gastritis and/or gastroenteritis, and improve histologic scores as well as other markers of disease activity.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 01327-001
    • Research Site
• Italy
  • Milano, Italy, 20122
    • Research Site
  • Padova, Italy, 35128
    • Research Site
  • Pisa, Italy, 56124
    • Research Site
• Japan
  • Bunkyo-ku, Japan, 113-8603
    • Research Site
  • Maebashi-shi, Japan, 371-8511
    • Research Site
  • Ogaki-shi, Japan, 503-8502
    • Research Site
  • Shinjuku-ku, Japan, 162-8655
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
• Poland
  • Staszów, Poland, 28-200
    • Research Site
• Spain
  • Sevilla, Spain, 41009
    • Research Site
• Ukraine
  • Kyiv, Ukraine, 04050
    • Research Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Research Site
    • Salt Lake City, Utah, United States, 84107
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 130 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Aged >= 12 years of age at the time of signing the ICF or informed consent or assent form.
• Confirmed diagnosis of EG/EGE for at least 3 months prior to screening.
• Baseline Eosinophilic gastritis, with or without duodenitis, or eosinophilic duodenitis alone confirmed by biopsy with a gastric count of ≥30 eosinophils/hpf in at least 5 hpfs and/or duodenal eosinophil count ≥30 eosinophils/hpf in at least 3 hpfs without any other cause for the gastrointestinal eosinophilia.
• Symptoms including at least moderate abdominal pain, nausea, bloating, early satiety, and/or loss of appetite
• Must be adherent to daily PRO assessments including at least 8 of 14 symptom assessments in the 14 days prior to randomization
• If on background medications for EG/EGE, the medications should be stable at least 4 weeks prior to the run-in period.
• Willing and able to comply with all study procedures and visit schedule including follow-up visits
• 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 gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, or celiac disease.
• Hypereosinophilic syndrome or eosinophilic granulomatosis with polyangiitis.
• Current malignancy, or history of malignancy, except for patients who have had basal cell, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date of informed consent.
• History of anaphylaxis to any biologic therapy or vaccine.
• Current active liver disease.
• Helminth parasitic infection diagnosed within 24 weeks prior to the date informed that has not been treated with or has failed to respond to standard of care therapy.
• Known immunodeficiency disorder including testing positive for HIV.
• Concomitant use of immunosuppressive medication.
• Receipt of live attenuated vaccines 30 days prior to date of informed consent or assent.
• Receipt of inactive vaccines within 7 days of informed consent or assent.
• Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group from 6 weeks prior to start of the run-in period and unable or unwilling to remain on a stable diet until the completion of Part A and C.
• Currently pregnant or breast-feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Benralizumab; This arm is a subcutaneous dose of Benralizumab	Biological: Benralizumab; Benralizumab is a humanized, afucosylated, monoclonal antibody that binds specifically to the IL-5Rα on the target cell and thus directly depletes eosinophils through antibody-dependent cell-mediated cytotoxicity. Benralizumab has been widely approved for treatment of asthma.; Other Names: Fasenra
Placebo Comparator: Placebo; This arm is a subcutaneous dose of Placebo	Biological: Placebo; Placebo will be injected as a comparator to injection with Benralizumab to examine effect on both the signs and symptoms of EG/EGE and the underlying eosinophilic inflammation, with dual primary outcome variables

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving a histological response in the stomach and/or in the duodenum	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Absolute change from baseline in SAGED (Symptom Assessment for Gastrointestinal Eosinophilic Diseases) Score (range: 0-50). SAGED score measures gastrointestinal symptoms with higher scores meaning worse outcome	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change in tissue eosinophils	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Proportion achieving treatment response	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Diarrhea-free days	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Frequency of diarrhea episodes	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Vomiting-free days	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Frequency of vomiting episodes	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Proportion of patients with no rescue corticosteroid use	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Health-related quality of life measured as change from baseline in SF-36v2 (the Short Form 36-item Health Survey, Version 2) which has two components: Physical Component Summary (PCS) and Mental Component Summary (MCS).	The score range for PCS and MCS is 0-100; higher scores indicate better health state. Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Diarrhea and constipation free days	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Clinically meaningful symptom change. Time to clinically meaningful change in SAGED score (range: 0-50) measures gastrointestinal symptoms with higher scores meaning worse outcome.	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
PROMIS Fatigue 7a score	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
PAGI-QoL score	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
PAGI-SYM score	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Week 24
Pharmacokinetics of benralizumab in patients (with EG/EGE)	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Minimum 24 weeks
Immunogenicity of benralizumab in patients (with EG/EGE)	Given the decision to stop recruitment to the study, it will not be possible to assess objectives with the data collected during Part A.	Minimum 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability - Incidence of Treatment-Emerged AEs and SAEs	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Week 52

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Marc E. Rothenberg, MD, PhD, Cincinnati Children's Hospital Medical Center 3333 Burnet Ave, Cincinnati Ohio 45229, United States

Publications and helpful links

Helpful Links

• 909_HUDSON_Poster_non-US.pdf
• 909_HUDSON_Poster_US-enUS.pdf

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Actual): February 13, 2024
• Study Completion (Actual): February 13, 2024

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: February 15, 2022
• First Posted (Actual): February 23, 2022

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Eosinophilic Gastritis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Benralizumab; Stomach Diseases
• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Hypersensitivity; Esophageal Diseases; Esophagitis; Leukocyte Disorders; Gastritis; Gastroenteritis; Eosinophilic Esophagitis; Enteritis; Eosinophilia; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: D3258C00001; 2021-000085-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymised individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
• IPD Sharing 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 refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de- identified individual patient-level data in an approved sponsor 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes