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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) (HUDSON GI)

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

12

Patients were randomly assigned in a 1:1 ratio to receive either benralizumab 30 mg or placebo at 4-week intervals. Randomization will be stratified by location of disease (EG with or without duodenal involvement vs duodenal disease alone) and baseline steroid use (categorical, Yes/No). Patients with symptomatic and histologically active EG/EGE aged at least 12 years were eligible for inclusion in this study. The study planned to randomize a minimum of approximately 210 and a maximum of approximately 230 participants. Enrollment was terminated after the enrollment of 34 participants, of which 12 were randomized. - Age, Categorical Benralizumab: 0 (<=18 years), 5 (between 18 and 65 years), 1 (>=65 years) Placebo: 1 (<=18 years), 4 (between 18 and 65 years), 1 (>=65 years) -Sex Benralizumab: 5 (female), 1 (male) Placebo: 1 (female), 2 (male) -Race Benralizumab: 1 (asian), 5 (white) Placebo: 1 (black or african american), 4 (white), 1 (unknown or not reported)

A total of 34 participants were screened and 12 participants were randomised and treated. 3 participants (25.0%) discontinued study treatment during the 24-week double-blind placebo-controlled treatment period. A total of 7 participants (58.3%) completed the double-blind study period and then moved to the open-label treatment period, and 2 participants (16.7%) moved to the open-label extension phase due to CSP change before completion of the double-blinded treatment period. 9 participants (75.0%) enrolled in the open-label extension of the study. Of those, 2 participants (16.7%) discontinued the open-label extension treatment with study drug but completed study follow-up. The remaining 7 participants (58.3%) completed the open-label extension treatment period.

During this period of the study, AEs were reported in a total of 5 of the 6 participants (83.3%) in the benralizumab groups and 1 of the 3 participants (33.3%) in the placebo group switched to benralizumab. There were no SAEs, no AEs leading to discontinuation of benralizumab, no AEs with the outcome of death were reported for any participant. All the AEs were reported as mild or moderate in intensity. There were no clinically meaningful changes in mean values from baseline for haematology variables, clinical chemistry laboratory variables, or urinalysis variables.

As the study was terminated and final sample size was not sufficient to carry out statistical analyses, the primary and secondary endpoints of the study could not be evaluated.

As the final sample size was not sufficient to carry out statistical analyses, the primary and secondary endpoints of the study could not be evaluated. From the 24-week double-blinded and the open-label extension periods, the safety and tolerability findings conclude that benralizumab was well-tolerated, and no new safety concerns were identified.

https://clinicaltrials.gov/study/NCT05251909?tab=results

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210500

Ageishi Yuji

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi

RD-clinical-information-Japan@astrazeneca.com

Ageishi Yuji

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi

+81-6-4802-3533

RD-clinical-information-Japan@astrazeneca.com

Complete

Jan. 14, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Aged 12 or more years of age at the time of signing the ICF or infromed 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 or more eosinophilis/hpf in at least 5 hpfs and/or duodenal eosinophil count 30 or more 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(comfirmed by the Investigator)from randomization throughout the study duration and within 12 weeks after last dose if IP.

- 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 malinancy, or history of malignancy, expect for patients who have bad basal cell, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligble 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 Week 52.

- Currently pregnant or breast-feeding

Both

Eosinophilic gastritis, Eosinophilic gastroenteritis

The patients are planned to be randomly assigned to receive either a fixed SC dose of Benralizumab or placebo once monthly in a 24 week double-blind period followed by assessments during an open-label Benralizumab treatment period.

- Proportion of patients achieving a histological response in the stomach and/or in the duodenum(at Week24)

- Absolute change in symptoms of EG/EGE(at Week24)

+81-3-3202-7181

June. 24, 2021

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