Benralizumab for Eosinophilic Gastritis (BEGS)

NCT03473977 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2017-1701
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of Benralizumab (Anti-IL5RA) in Subjects With Eosinophilic Gastritis.

Conditions

Eosinophilic Gastritis or Gastroenteritis

Outcome Measures

Primary Outcomes (1)

• Percent of Patients in Histological Remission (<30 Eos/Hpf)

  Percent of patients in histologic remission in drug versus placebo groups. Remission is defined as gastric peak eosinophil count \< 30 eosinophils per high powered field (eos/hpf).

  12 weeks after start of treatment

Secondary Outcomes (6)

• Change in Gastric Endoscopic Score (Lanza)

  12 weeks after start of treatment

• Change in Gastric Histology Score

  12 weeks after start of treatment

• Change in Blood Eosinophil Count

  12 weeks after start of treatment

• Change in Eosinophilic Gastritis Diagnostic Panel

  12 weeks after start of treatment

• Change in Gastric Peak Eosinophil Count

  12 weeks after starting treatment

Study Arms (2)

Benralizumab

EXPERIMENTAL

Subcutaneous dose of 30 mg of Benralizumab every 4 weeks

Biological: Benralizumab

Placebo

PLACEBO COMPARATOR

Subcutaneous dose of Placebo every 4 weeks

Biological: Placebo

Interventions

Benralizumab BIOLOGICAL

Benralizumab (anti-IL5Ra) will be injected every 4 weeks in doses of 30 mg (total of 3 injections) in subjects with active Eosinophilic Gastritis.

Also known as: Fasenra

Benralizumab

Placebo BIOLOGICAL

Placebo will be injected every 4 weeks (total of 3 injections) as a comparator to Benralizumab in subjects with active Eosinophilic Gastritis.

Placebo

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
• Males and females between the ages of 12-60 years with confirmed diagnosis of EG involving stomach; involvement of eosinophilic inflammation in other gastrointestinal segments will be allowed but not required or sufficient.
• Histologically active EG at time of screening, with a peak Gastric count of ≥ 30 eos/hpf in at least 5 hpfs.
• Must be symptomatic (defined as having experienced symptoms within 4 weeks prior to enrollment).
• Blood eosinophilia (defined as having an absolute eosinophil count \> 500 cells per microliter of blood) at least once during the 6 months prior to enrollment.
• Must be on baseline anti-eosinophilic gastritis/eosinophilic gastroenteritis therapy as long as there is agreement to not change their dosage unless medically indicated; OR, must have failed anti-eosinophilic gastritis/eosinophilic gastroenteritis in the past, including diet therapy.
• Clinical symptoms (i.e., abdominal pain, bloating, vomiting, diarrhea) severe enough to impact daily life (e.g., school/work attendance, social activities) ≥ 2 days/week for 3 of the 4 weeks prior to enrollment despite treatment (such as diet, proton pump inhibitors or corticosteroids).
• Female subjects: Women of childbearing potential (WOCBP) must use an effective form of birth control (confirmed by the Investigator). Effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective intrauterine device/ levonogestrel Intrauterine system, Depo-Provera(tm) injections, oral contraceptive, and Evra Patch(tm) or Nuvaring(tm). WOCBP must agree to use effective method of birth control, as defined above, from enrollment, throughout the study duration and within 16 weeks after last dose of investigational product, and have negative serum pregnancy test result on Visit 1.
• Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of visit -1 without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
• Women ≥50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
• All male subjects who are sexually active must agree to use an acceptable method of contraception (condom with or without spermicide, vasectomy) from Visit 1 until 16 weeks after their last dose.

You may not qualify if:

• Concurrent H. pylori gastritis or parasitic infection
• Other gastrointestinal disorders such as Crohn's disease, inflammatory bowel disease, or Celiac disease, eosinophilic granulomatosis with polyangiitis (EGPA), drug hypersensitivity or connective tissue rheumatological disorders,
• Esophageal stricture that prevents the easy passage of a standard endoscope
• Use of any investigational biologic drug within 6 months prior to screening
• Hypereosinophilic syndrome, defined by multiple organ involvement (with the exception of atopic disease or EGID) and persistent blood absolute eosinophil count ≥1500/mcL.
• History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent, and assent when applicable was obtained. Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent, and assent when applicable, was obtained.
• A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy.
• Pregnant or nursing
• Receipt of any investigational non-biologic within 30 days or 5 half-lives prior to visit 1, whichever is longer.
• A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
• Any other medical illness that precludes study involvement
• Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to be enrolled.
• Patients who are currently receiving or have previously received benralizumab or any other type of anti-interleukin therapy (i.e. mepolizumab, reslizumab, lebrikizumab etc.) within the last 6 months or 5 half-lives whichever is longer.
• History of anaphylaxis to any biologic therapy or vaccine.
• Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• AstraZeneca: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

• Kliewer KL, Murray-Petzold C, Collins MH, Abonia JP, Bolton SM, DiTommaso LA, Martin LJ, Zhang X, Mukkada VA, Putnam PE, Kellner ES, Devonshire AL, Schwartz JT, Kunnathur VA, Rosenberg CE, Lyles JL, Shoda T, Klion AD, Rothenberg ME. Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Gastroenterol Hepatol. 2023 Sep;8(9):803-815. doi: 10.1016/S2468-1253(23)00145-0. Epub 2023 Jun 16.

  PMID: 37336228 DERIVED

MeSH Terms

Conditions

Eosinophilic enteropathy; Gastroenteritis

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases

Results Point of Contact

• Title: Marc E. Rothenberg, MD, PhD
• Organization: Cincinnati Children's Hospital Medical Center

marc.rothenberg@cchmc.org

513-636-7177

Study Officials

• Marc E Rothenberg, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant/care providers, investigators, and outcome assessor (pathology) were blinded to assignment. Randomization performed by external investigational pharmacy staff (dispenses the drug/placebo).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will receive doses of drug or placebo. Optional open label extensions available following the double blind period.

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 22, 2018
• Study Start: April 23, 2018
• Primary Completion: June 22, 2020
• Study Completion: January 12, 2022
• Last Updated: February 3, 2022
• Results First Posted: August 17, 2021

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)