The objective of this Phase 3 study is to investigate the safety and efficacy of benralizumab as a treatment for patients with eosinophilic gastritis and/or gastro-enteritis.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective Part A/B: To compare the effect of benralizumab 30 mg every 4
weeks (Q4W) with placebo on histologic signs and gastrointestinal symptoms in
patients with eosinophilic gastritis and/or gastroenteritis.
Histology-based Dual-primary endpoints/variables: Proportion of patients
achieving a histological response (defined as <=6 eosinophils/hpf in the stomach
and/or, <=15 eosinophils/hpf in the duodenum) at Week 24.
Symptom-based dual primary endpoint: Symptom Endpoint: Absolute change from
baseline in SAGED Score at Week 24
Symptom based Endpoint: Absolute change from baseline in SAGED Score at Week 24
Secondary outcome
Secondary objectives Part A/B: To compare the effect of benralizumab 30 mg Q4W
with placebo on clinical features of eosinophilic gastritis/ gastroenteritis
and disease activity.
Key secondary endpoint: :
* Percentage change from baseline in tissue eosinophils (stomach and/or
duodenum if applicable) at Week 24.
* Proportion of patients who achieve treatment response: tissue remission (<=6
eosinophils/hpf in the stomach and <=15 eosinophils/hpf in the duodenum, if
applicable) and improvement in symptoms at Week 24
* Change from baseline in proportion of vomiting free days, and change from
baseline in frequency of vomiting episodes
* Change from baseline in proportion of diarrheafree days, and change from
baseline in frequency of diarrhea episodes
* Change from baseline in proportion of days both diarrhea and constipation free
* Time to clinically meaningful improvement in SAGED score
* Change from baseline in PROMIS Fatigue 7a score and PAGI-SYM score at Week 24
Safety objective: To assess the safety of benralizumab in patients with
eosinophilic gastritis and/or gastroenteritis.
Safety endpoint: Adverse Events, vital signs, physical exam, and laboratory
parameters.
Background summary
Eosinophilic gastritis and eosinophilic gastroenteritis (EG/EGE) are rare
chronic allergic inflammatory disorders of the gastrointestinal tract
characterized by increased infiltration of eosinophils in the stomach and
duodenum tissues and accompanying gastrointestinal
symptoms, such as nausea, vomiting, abdominal pain, and diarrhea. Although
these disorders have been increasingly recognized and diagnosed in both adults
and adolescents, there are currently neither established diagnostic criteria
nor treatment guidelines and no approved
treatments. Histopathology of affected tissue demonstrates high numbers of
eosinophils and evidence of eosinophilic degranulation. This increase,
especially when associated with aggregation, degranulation and infiltration of
squamous epithelium along with architectural changes in the
mucosa, indicates a pathologic process, and the histopathology of affected
tissue demonstrates high numbers of eosinophils and evidence of eosinophilic
degranulation (Egan and Furuta 2018). Currently there are no established
treatment guidelines and no approved treatments for
EG/EGE. Dietary elimination therapy and corticosteroids (systemic and topical)
are the most common treatments but are suboptimal and have limitations.
Benralizumab is a humanized, afucosylated, monoclonal antibody that binds
specifically to the IL-5Rα on target cells, resulting in the depletion of
eosinophils through antibody-dependent cell-mediated cytotoxicity. This
mechanism of action makes benralizumab a potential treatment for patients with
symptomatic and histologically active EG/EGE. This 3-part Phase 3 study will 1)
validate a patient-reported outcome (PRO)
instrument for EG/EGE symptoms while providing preliminary efficacy and safety
data (24-week Part A), 2) provide pivotal efficacy and safety data for EG/EGE
for the registration of this indication (24-week Part B), and 3) provide
long-term efficacy and safety data of benralizumab (Part C) during an open
label extension.
Study objective
The objective of this Phase 3 study is to investigate the safety and efficacy
of benralizumab as a treatment for patients with eosinophilic gastritis and/or
gastro-enteritis.
Study design
This is a 3-part study. Part A and Part B have identical designs (ie,
parallel-group, randomized, double-blinded, placebo-controlled with 24-week
treatment periods), with enrollment/randomization performed sequentially. Part
A will be enrolled first, followed by Part B. Parts A and Parts B will include
approximately 70 and 150 unique participants in total with eosinophilic
gastritis (with or without eosinophilic duodenitis) or duodenal-only disease,
including a minimum of at least 50 and 110 patients with EG (with or without
duodenal involvement) in each part, respectively. After a 4-week to 8-week
run-in period, symptomatic participants with EG with or without duodenitis and
patients with eosinophilic duodenitis only, on stable background medications
and diet, with histologically-confirmed disease will be randomized 1:1 to
benralizumab or placebo treatments. Part A will be enrolled first, followed by
Part B. After completing Part A or Part B, participants will continue to Part
C, an extended open-label benralizumab treatment period. Participants will
remain on stable background medication and diet throughout the first 52 weeks
of the study (including Part A/B and the
first 28 weeks of Part C). After 52 weeks of treatment with stable diet and
medications, investigators may adjust background medication and diet
restrictions as clinically indicated.
Intervention
After a 4-week to 8-week run-in period, eligible patients with gastritis
and/or gastro-enteritis will be randomized 1:1 to24 weeks of subcutaneous
treatment with benralizumab 30 mg Q4W or matching placeboQ4W, in either Part A
or Part B. Subsequently, all participants will receive benralizumab 30 mg Q4W
subcutaneously in an open-label period, Part C, which is intended to allow
patients at least 1 year of treatment with open-label benralizumab treatment.
Patients will maintain stable background medication and diet regimen for EG/EGE
treatment through Week 52. After this timepoint investigators may consider
clinically appropriate adjustments to background medications and dietary
restrictions.
Study burden and risks
For the double-blind treatment period, the subject is asked to visit the
hospital at least 8 times. Each visit will last 1-4 hours. For the open label
treatment period, the subject may self-administer the study drug at home during
two consecutive visits. (from week 32) This will then be a telephone
appointment. The next (third) visit will take place in the hospital. The
subject will receive study drug 14 times for 52 weeks. If the subject
participates in the study extension, the subject will receive study drug 20
times over 76 weeks. Thereafter, the subject can participate in an extension
period and receive the study drug every 4 weeks. For the open label extension
treatment period from week 76, it is also possible to administer benralizumab
at home for 2 visits and then again during a hospital visit. This visit will
last 1-2 hours.
The study drug can cause allergic reactions. A study physician will be present
during the administration of the studydrug and will observe the subject for at
least one hour after administration of the studydrug. In addition, the subject
may suffer from side effects of the studydrug. Blood samples will be taken
during the study. The total blood volume to be collected during the first year
is 190 ml. The subject will receive a physical examination at each visit. The
subject will undergo an endoscopy including biopsies at least 3 times during
the study. Endoscopies involve risks and inconveniences, but the number of
endoscopies is equal to the number of endoscopies in standard practice. An ECG
is made during one visit. Women of childbearing potential will be required to
provide a urine sample to take a pregnancy test during the screening visit and
each time prior to study drug administration, The subject is asked to complete
questionnaires during each hospital visit. The subject will complete daily,
weekly and monthly questionnaires in an electronic diary. This will take about
10 minutes per day.
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
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 Week 52.
· Currently pregnant or breast-feeding.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-000085-14-NL |
| ClinicalTrials.gov | NCTnummervolgt |
| CCMO | NL77322.018.21 |