Clinical trial NCT03473977: Benralizumab for Eosinophilic Gastritis (BEGS)
Official title: A Randomized, Double-Blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy of Benralizumab (Anti-IL5RA) in Subjects With Eosinophilic Gastritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Eosinophilic Gastritis or Gastroenteritis
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2018-03-22
Enrollment: 26
Sex: ALL
Minimum age (years): 12
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will receive doses of drug or placebo. Optional open label extensions available following the double blind period.
Primary purpose: TREATMENT

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

Detailed description: Primary Objective:

To assess the efficacy of repeat subcutaneous (SC) doses of benralizumab, compared with placebo, to reduce eosinophilic inflammation in the gastrointestinal tract of patients with Eosinophilic Gastritis

Secondary Objectives:

To assess changes in endoscopic score, histological features, blood and biopsy eosinophil counts, clinical symptoms, and gastric tissue transcriptome before and after treatment with benralizumab.

26 subjects are planned to be enrolled into the study at Cincinnati Children's Hospital Medical Center. Qualifying Subjects will receive subcutaneous injections every 4 weeks (3 total) of benralizumab/Placebo, followed by optional Open Label Extension periods.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percent of Patients in Histological Remission (<30 Eos/Hpf)
timeFrame: 12 weeks after start of treatment
Secondary outcomes:
measure: Change in Gastric Endoscopic Score (Lanza)
timeFrame: 12 weeks after start of treatment
measure: Change in Gastric Histology Score
timeFrame: 12 weeks after start of treatment
measure: Change in Blood Eosinophil Count
timeFrame: 12 weeks after start of treatment
measure: Change in Eosinophilic Gastritis Diagnostic Panel
timeFrame: 12 weeks after start of treatment
measure: Change in Gastric Peak Eosinophil Count
timeFrame: 12 weeks after starting treatment
measure: Change in Clinical Symptoms
timeFrame: 12 weeks after start of treatment
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Marc E Rothenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: