ClinicalTrials.gg
Sign In
CompletedNCT03473977BEGSUpdated Feb 3, 2022Results posted

Benralizumab for Eosinophilic Gastritis (BEGS)

A Phase 2/3 interventional study of Benralizumab and Placebo in Eosinophilic Gastritis or Gastroenteritis, sponsored by Children's Hospital Medical Center, Cincinnati. Completed at 1 site in United States. Open to participants aged 12 Years to 60 Years. Per ClinicalTrials.gov, last updated 2022-02-03.

Sponsored by Children's Hospital Medical Center, Cincinnati · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
26
Allocation
Randomized
Ages
12 Years to 60 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Eosinophilic Gastritis or Gastroenteritis

Browse trials for

03

In context

Gastroenteritis

244 studies on the registry are indexed under Gastroenteritis; 15 are open to participants now.

This study's enrollment of 26 is below the median of 125 across 160 interventional studies indexed under Gastroenteritis.

Browse Gastroenteritis studies →

Lead sponsor

Children's Hospital Medical Center, Cincinnati is the lead sponsor of 673 studies on the registry; 134 are open to participants now.

Of its 56 completed or terminated interventional studies of FDA-regulated products, 31 (55%) have results posted.

Browse Children's Hospital Medical Center, Cincinnati studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Benralizumab

    Subcutaneous dose of 30 mg of Benralizumab every 4 weeks

    Biological: Benralizumab

  • Placebo comparator
    Placebo

    Subcutaneous dose of Placebo every 4 weeks

    Biological: Placebo

Interventions

  • BiologicalBenralizumab

    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

  • BiologicalPlacebo

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

06

What researchers measure

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).

    Time frame: 12 weeks after start of treatment

Secondary outcomes

  1. Change in Gastric Endoscopic Score (Lanza)

    The gastric endoscopic score (Lanza) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (granularity, nodularity, erosion/ulceration, friability, erythema). Total score is the maximum score of the five feature scores from the body, antrum, or fundus. Total scores range from 0 - 14. Change in total endoscopic reference score is defined as post-treatment score minus pre-treatment score. Changes in scores are compared between drug and Placebo. A reduction (negative change) in score indicates improvement.

    Time frame: 12 weeks after start of treatment

  2. Change in Gastric Histology Score

    The gastric histology score quantifies inflammatory and structural histologic abnormalities in the stomach. Total score is the sum of features scores divided by the maximum possible score for the biopsy. Features include lamina propria eosinophil sheets, periglandular circumferential collars, eosinophils in surface epithelium, eosinophil glandulitis, eosinophil gland abscesses, eosinophils in muscularis mucosa, lamina propria fibroplasia, lamina propria smooth muscle hyperplasia, reactive epithelial changes, acute inflammatory cells, and surface erosion. Total scores range from 0 - 1. Change in gastric total histology scoring is defined as post-treatment total score minus pretreatment total score. Changes in scores are compared between drug and placebo. A reduction (negative change) in score indicates improvement.

    Time frame: 12 weeks after start of treatment

  3. Change in Blood Eosinophil Count

    Change in absolute eosinophil counts (cells per microliter) is defined as post treatment counts minus pre-treatment counts. Changes in counts are compared between drug and Placebo. A decrease in count is expected due to the effects of the drug.

    Time frame: 12 weeks after start of treatment

  4. Change in Eosinophilic Gastritis Diagnostic Panel

    The transcriptomic signature of gastric biopsy samples was obtained using real-time polymerase chain reaction amplification on the EG diagnostic panel (EGDP) comprising a set of 48 gastric transcripts. The EGDP value was calculated by summing delta CT (threshold cycle) values of the most highly dysregulated genes. Change is defined as post treatment value minus pre-treatment value. An increase (positive change) indicates improvement (normalization of gene expression).

    Time frame: 12 weeks after start of treatment

  5. Change in Gastric Peak Eosinophil Count

    Change in gastric peak eosinophil count is defined as post-treatment peak count minus pre-treatment peak count. Changes in peak count are compared between Drug and Placebo. A reduction (negative change) in peak count indicates improvement.

    Time frame: 12 weeks after starting treatment

  6. Change in Clinical Symptoms

    The symptom of dyspepsia (SODA) questionnaire captures symptoms associated with gastric dyspepsia including symptoms associated with "pain" and "non-pain" as well as general "satisfaction" with present symptoms. The scores range from 0 to 47 for pain; 0 to 35 for non-pain, and 0 to 23 for satisfaction. Higher scores indicate more frequent and/or severe symptoms for pain and non-pain. Higher scores indicate greater Satisfaction. Change in score is defined as post-treatment total score minus pre-treatment total score. A reduction (negative change) indicates improvement in pain and non-pain. An increase (positive change) indicates improvement in satisfaction.

    Time frame: 12 weeks after start of treatment

07

Results

Posted Aug 17, 2021

Participant flow

Participants were recruited from an eosinophilic disorder specialty clinic in the US between April 2018 and January 2020.

Participant flow — Overall Study
MilestoneBenralizumabPlacebo
Started1313
Completed1313
Not completed00

Outcome measures

PrimaryPercent 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).

Time frame:
12 weeks after start of treatment
Reported as:
Number · percentage of participants
Percent of Patients in Histological Remission (<30 Eos/Hpf)
percentage of participantsBenralizumabPlacebo
Percent of Patients in Histological Remission (<30 Eos/Hpf)778
Statistical analysis
  • Benralizumab vs Placebo · Fisher Exact · p = 0.0001
SecondaryChange in Gastric Endoscopic Score (Lanza)

The gastric endoscopic score (Lanza) utilizes standardized criteria for the presence and degree of 5 major endoscopic features (granularity, nodularity, erosion/ulceration, friability, erythema). Total score is the maximum score of the five feature scores from the body, antrum, or fundus. Total scores range from 0 - 14. Change in total endoscopic reference score is defined as post-treatment score minus pre-treatment score. Changes in scores are compared between drug and Placebo. A reduction (negative change) in score indicates improvement.

Time frame:
12 weeks after start of treatment
Reported as:
Median · score on a scale
Change in Gastric Endoscopic Score (Lanza)
score on a scaleBenralizumabPlacebo
Change in Gastric Endoscopic Score (Lanza)-1.0 (-1.0 to 0.0)0.0 (-2.0 to 0.0)
Statistical analysis
  • Benralizumab vs Placebo · Kruskal-Wallis · p = 0.75
SecondaryChange in Gastric Histology Score

The gastric histology score quantifies inflammatory and structural histologic abnormalities in the stomach. Total score is the sum of features scores divided by the maximum possible score for the biopsy. Features include lamina propria eosinophil sheets, periglandular circumferential collars, eosinophils in surface epithelium, eosinophil glandulitis, eosinophil gland abscesses, eosinophils in muscularis mucosa, lamina propria fibroplasia, lamina propria smooth muscle hyperplasia, reactive epithelial changes, acute inflammatory cells, and surface erosion. Total scores range from 0 - 1. Change in gastric total histology scoring is defined as post-treatment total score minus pretreatment total score. Changes in scores are compared between drug and placebo. A reduction (negative change) in score indicates improvement.

Time frame:
12 weeks after start of treatment
Reported as:
Median · score on a scale
Change in Gastric Histology Score
score on a scaleBenralizumabPlacebo
Change in Gastric Histology Score-0.33 (-0.41 to -0.27)-0.04 (-0.10 to 0.05)
Statistical analysis
  • Benralizumab vs Placebo · Kruskal-Wallis · p = 0.006
SecondaryChange in Blood Eosinophil Count

Change in absolute eosinophil counts (cells per microliter) is defined as post treatment counts minus pre-treatment counts. Changes in counts are compared between drug and Placebo. A decrease in count is expected due to the effects of the drug.

Time frame:
12 weeks after start of treatment
Reported as:
Median · cells per microliter
Change in Blood Eosinophil Count
cells per microliterBenralizumabPlacebo
Change in Blood Eosinophil Count-1060 (-1740 to -830)-160 (-710 to 120)
Statistical analysis
  • Benralizumab vs Placebo · Kruskal-Wallis · p = 0.004
SecondaryChange in Eosinophilic Gastritis Diagnostic Panel

The transcriptomic signature of gastric biopsy samples was obtained using real-time polymerase chain reaction amplification on the EG diagnostic panel (EGDP) comprising a set of 48 gastric transcripts. The EGDP value was calculated by summing delta CT (threshold cycle) values of the most highly dysregulated genes. Change is defined as post treatment value minus pre-treatment value. An increase (positive change) indicates improvement (normalization of gene expression).

Time frame:
12 weeks after start of treatment
Reported as:
Mean · delta threshold cycle
Change in Eosinophilic Gastritis Diagnostic Panel
delta threshold cycleBenralizumabPlacebo
Change in Eosinophilic Gastritis Diagnostic Panel29 ± 31-12 ± 23
Statistical analysis
  • Benralizumab vs Placebo · t-test, 2 sided · p = 0.0058
SecondaryChange in Gastric Peak Eosinophil Count

Change in gastric peak eosinophil count is defined as post-treatment peak count minus pre-treatment peak count. Changes in peak count are compared between Drug and Placebo. A reduction (negative change) in peak count indicates improvement.

Time frame:
12 weeks after starting treatment
Reported as:
Median · eosinophils per high power field
Change in Gastric Peak Eosinophil Count
eosinophils per high power fieldBenralizumabPlacebo
Change in Gastric Peak Eosinophil Count-132 (-196 to -82)-29 (-89 to 0)
Statistical analysis
  • Benralizumab vs Placebo · Kruskal-Wallis · p = 0.014
SecondaryChange in Clinical Symptoms

The symptom of dyspepsia (SODA) questionnaire captures symptoms associated with gastric dyspepsia including symptoms associated with "pain" and "non-pain" as well as general "satisfaction" with present symptoms. The scores range from 0 to 47 for pain; 0 to 35 for non-pain, and 0 to 23 for satisfaction. Higher scores indicate more frequent and/or severe symptoms for pain and non-pain. Higher scores indicate greater Satisfaction. Change in score is defined as post-treatment total score minus pre-treatment total score. A reduction (negative change) indicates improvement in pain and non-pain. An increase (positive change) indicates improvement in satisfaction.

Time frame:
12 weeks after start of treatment
Reported as:
Median · score on a scale
Change in Clinical Symptoms
score on a scaleBenralizumabPlacebo
Pain score-3.0 (-9.0 to 0.0)-2.0 (-6.0 to 0.0)
Non-pain score-2.0 (-4.0 to 0.0)-1.0 (-3.0 to 1.0)
Satisfaction1.0 (0.0 to 5.0)2.5 (0.0 to 5.0)
Statistical analysis
  • Benralizumab vs Placebo · Kruskal-Wallis · p = 0.78
  • Benralizumab vs Placebo · Kruskal-Wallis · p = 0.34
  • Benralizumab vs Placebo · Kruskal-Wallis · p = 0.66

Adverse events

Collected over From informed consent to 4 weeks after the end of the 12 week double-blind. On average, this was approximately 20 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Benralizumab0/13 (0%)0/13 (0%)11/13 (84.6%)
Placebo0/13 (0%)0/13 (0%)8/13 (61.5%)
Most frequent other events
Showing 10 of 37
Most frequent other events
EventBenralizumabPlacebo
HeadacheNervous system disorders6/132/13
VomitingGastrointestinal disorders2/133/13
AnemiaBlood and lymphatic system disorders2/130/13
Abdominal PainGastrointestinal disorders2/132/13
FeverGeneral disorders2/130/13
ArthralgiaMusculoskeletal and connective tissue disorders2/130/13
DizzinessNervous system disorders2/131/13
BelchingGastrointestinal disorders0/131/13
BloatingGastrointestinal disorders1/130/13
ConstipationGastrointestinal disorders0/131/13

Baseline characteristics

Age, Continuous
Age, Continuous(years)BenralizumabPlaceboTotal
Mean14.9 ± 2.024.1 ± 7.919.5 ± 7.3
Sex: Female, Male
Sex: Female, Male(Participants)BenralizumabPlaceboTotal
Female437
Male91019
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)BenralizumabPlaceboTotal
Hispanic or Latino112
Not Hispanic or Latino121224
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)BenralizumabPlaceboTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American101
White121325
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)BenralizumabPlaceboTotal
United States131326
Gastric Peak Eosinophil Count
Gastric Peak Eosinophil Count(eosinophils per high power field)BenralizumabPlaceboTotal
Median210 (93 to 230)147 (119 to 208)157 (93 to 230)
Gastric Histology Score
Gastric Histology Score(score on a scale)BenralizumabPlaceboTotal
Median0.55 (0.50 to 0.64)0.50 (0.45 to 0.59)0.50 (0.45 to 0.64)
Gastric Endoscopy Score (Lanza)
Gastric Endoscopy Score (Lanza)(score on a scale)BenralizumabPlaceboTotal
Median4.0 (3.0 to 5.0)6.0 (5.0 to 8.0)5.0 (4.0 to 6.5)

5 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229, United States
09

References and documents

Publications

  • 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. PubMed 37336228 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 3, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Apr 2018 to primary completion in Jun 2020, 25 months.

Results were first posted in Aug 2021, 1 year 1 month after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 28, 2018
First posted
Mar 22, 2018
StartActual
Apr 23, 2018
Primary completionActual
Jun 22, 2020
CompletionActual
Jan 12, 2022
Results first posted
Aug 17, 2021
Last update
Feb 3, 2022
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 3, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03473977
Lead sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
AstraZeneca
Responsible party
Sponsor
First posted
Mar 22, 2018
Start date
Apr 23, 2018
Primary completion
Jun 22, 2020
Completion
Jan 12, 2022
Results posted
Aug 17, 2021
Last update
Feb 3, 2022

Study contacts

Marc E Rothenberg, MD, PhD
principal investigator · Children's Hospital Medical Center, Cincinnati

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Benralizumab

Other studies in this condition

Gastroenteritis →

Other studies from this sponsor

Children's Hospital Medical Center, Cincinnati →

Start the discussion