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

Eosinophilic Gastroenteritis Clinical Trial

— HUDSON GI  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05251909
• Other study ID #: D3258C00001
• Secondary ID: 2021-000085-14
• Status: Completed
• Phase: Phase 3
• Start date: January 18, 2022
• Est. completion date: February 13, 2024

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: February 13, 2024
• Est. primary completion date: February 13, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Enteritis
• Eosinophilia
• Eosinophilic Esophagitis
• Eosinophilic Gastritis
• Eosinophilic Gastroenteritis
• Gastritis
• Gastroenteritis

Intervention

Biological:
• Benralizumab
Benralizumab is a humanized, afucosylated, monoclonal antibody that binds specifically to the IL-5Ra on the target cell and thus directly depletes eosinophils through antibody-dependent cell-mediated cytotoxicity. Benralizumab has been widely approved for treatment of asthma.
• 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

Locations

Country	Name	City	State
Brazil	Research Site	Sao Paulo
Italy	Research Site	Milano
Italy	Research Site	Padova
Italy	Research Site	Pisa
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Maebashi-shi
Japan	Research Site	Ogaki-shi
Japan	Research Site	Shinjuku-ku
Netherlands	Research Site	Amsterdam
Poland	Research Site	Staszów
Spain	Research Site	Sevilla
Ukraine	Research Site	Kyiv
United States	Research Site	Boston	Massachusetts
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Rochester	Minnesota
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Salt Lake City	Utah
Vietnam	Research Site	Hanoi

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Brazil,  Italy,  Japan,  Netherlands,  Poland,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety and tolerability - Incidence of Treatment-Emerged AEs and SAEs	Adverse Events (AEs) and Serious Adverse Events (SAEs)	Week 52
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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