Clinical trial NCT05251909: Efficacy and Safety of Benralizumab in Patients With Eosinophilic Gastritis and/or Gastroenteritis (The HUDSON GI Study)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Eosinophilic Gastritis
Eosinophilic Gastroenteritis
Keywords: Benralizumab
Eosinophilic Gastritis
Gastroenteritis
Intestinal Diseases
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-02-23
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Maximum age (years): 130
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients achieving a histological response in the stomach and/or in the duodenum
timeFrame: Week 24
measure: 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
timeFrame: Week 24
Secondary outcomes:
measure: Percent change in tissue eosinophils
timeFrame: Week 24
measure: Proportion achieving treatment response
timeFrame: Week 24
measure: Diarrhea-free days
timeFrame: Week 24
measure: Frequency of diarrhea episodes
timeFrame: Week 24
measure: Vomiting-free days
timeFrame: Week 24
measure: Frequency of vomiting episodes
timeFrame: Week 24
measure: Proportion of patients with no rescue corticosteroid use
timeFrame: Week 24
measure: 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).
timeFrame: Week 24
measure: Diarrhea and constipation free days
timeFrame: Week 24
measure: Clinically meaningful symptom change. Time to clinically meaningful change in SAGED score (range: 0-50) measures gastrointestinal symptoms with higher scores meaning worse outcome.
timeFrame: Week 24
measure: PROMIS Fatigue 7a score
timeFrame: Week 24
measure: PAGI-QoL score
timeFrame: Week 24
measure: PAGI-SYM score
timeFrame: Week 24
measure: Pharmacokinetics of benralizumab in patients (with EG/EGE)
timeFrame: Minimum 24 weeks
measure: Immunogenicity of benralizumab in patients (with EG/EGE)
timeFrame: Minimum 24 weeks
Other outcomes:
measure: Safety and tolerability - Incidence of Treatment-Emerged AEs and SAEs
timeFrame: Week 52
Locations:
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Sao Paulo
country: Brazil
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Maebashi-shi
country: Japan
facility: Research Site
city: Ogaki-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Staszów
country: Poland
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
Study officials:
affiliation: Cincinnati Children's Hospital Medical Center 3333 Burnet Ave, Cincinnati Ohio 45229, United States
name: Marc E. Rothenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: