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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Eosinophilic Gastritis, Eosinophilic Gastroenteritis

Intervention / Treatment
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* Biological: Benralizumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Benralizumab<br>This arm is a subcutaneous dose of Benralizumab | Biological: Benralizumab<br>* 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.<br>* Other names: Fasenra;|
| Placebo Comparator: Placebo<br>This arm is a subcutaneous dose of Placebo | Biological: Placebo<br>* 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<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Benralizumab, Eosinophilic Gastritis, Gastroenteritis, Intestinal Diseases, Stomach Diseases, Gastrointestinal Diseases, Digestive System Diseases