The objective of this Phase 3 study is to investigate the safety and efficacy of benralizumab as a treatment for patients with eosinophilic esophagitis.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective: To evaluate the effect of benralizumab 30 mg Q4W on
histologic signs and symptoms of EoE in patients with symptomatic and
histologically active EoE.
Dual-primary endpoints/variables: Proportion of patients with a histologic
response at Week 24, defined as a peak esophageal intraepithelial eosinophil
count <= 6 eos/hpf and Changes from baseline in DSQ score at Week 24.
Secondary outcome
Secondary objectives:
To evaluate the effect of benralizumab 30 mg Q4W on clinical features of EoE
and disease activity.
Endpoints/variables:
- Key secondary endpoint: Changes from baseline in centrally-read EoE EREFS at
Week 24.
- Centrally-read biopsies for additional histopathology and tissue eosinophil
counts, including EoE-HSS, at Week 24.
- Dysphagia-free days as captured by the DSQ.
- Frequency of dysphagia episodes as captured by the EoE-3D.
- Changes from baseline in dysphagia associated pain, discomfort, and overall
severity as captured by the EoE-3D at Week 24.
- Changes from baseline in abdominal pain and nausea as captured by the daily
diary at Week 24.
To evaluate the effect of benralizumab 30 mg Q4W on patient reported QOL
measures.
Endpoints/variables:
- Changes from baseline in EoE-QoL-A at Week 24.
- SF-36 v2 Health Survey at Week 24.
To evaluate the effect of benralizumab 30 mg Q4W on healthcare resource
utilization due to EoE.
Endpoint/variable:
- Percent of patients with relevant concomitant procedures and healthcare
resource utilization during the study through Week 24.
To evaluate the effect of benralizumab 30 mg Q4W on patient reported measures
of disease severity and health status.
Endpoints/variables:
- PGI-S at Week 24.
- PGI-C at Week 24.
To assess the PK and immunogenicity of benralizumab 30 mg Q4W in patients with
EoE.
Endpoints/variables:
- Serum benralizumab concentration.
- ADA and nAb.
Background summary
Eosinophilic esophagitis is a chronic allergic inflammatory disorder of the
esophagus, defined histologically by esophageal inflammation of >=15 eosinophils
per high power field (eos/hpf). Typical symptoms include dysphagia and food
impaction in adolescents and adults.
There is a clinical unmet need for new therapies for use in patients with EoE.
Jorveza® (orodispersible budesonide tablet) was approved in the EU for the
treatment of EoE in adults in 2018, and there are no approved products for the
treatment of EoE in the paediatric population. Additionally, most current
treatment approaches are either burdened with compliance problems, and/or
limited efficacy, or reserved for the treatment of complications.
Benralizumab is a humanized, afucosylated, monoclonal antibody that binds
specifically to the IL-5Rα on the target cell and directly depletes eosinophils
through ADCC. The mechanism of action of benralizumab makes it a potential
treatment option for the high unmet need in patients with symptomatic and
histologically active EoE. Benralizumab has been or is being investigated in
patients with asthma, chronic obstructive pulmonary disease (COPD), HES, nasal
polyposis, eosinophilic granulomatosis with polyangiitis (EGPA), eosinophilic
chronic rhinosinusitis, and eosinophilic gastritis/gastroenteritis. The present
study (D3255C00001 [MESSINA]) represents the first clinical study dedicated to
the assessment of benralizumab in patients with EoE.
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 esophagitis.
Study design
This is a randomized, placebo-controlled, DB, parallel-group, multicenter,
Phase 3 study to compare the efficacy and safety of repeat dosing of
benralizumab versus placebo in male and female patients 12 to 65 years of age
with symptomatic and histologically active eosinophilic esophagitis (EoE).
Approximately 170 eligible patients with symptomatic and histologically active
EoE before randomization will be randomized in a 1:1 ratio to receive either 30
mg of benralizumab or placebo at 4-week intervals for a 24-week treatment
period (DB period). The randomization for adults will be stratified by region
(North America vs Rest of World [ROW]) and baseline steroid use. Patients who
complete the DB, placebo-controlled treatment period on investigational product
(IP) will continue into an OL treatment period with benralizumab 30 mg Q4W
until Week 52 (OL period). All compliant patients who complete the 52-week
treatment period (the 24-week DB treatment period and the 28-week OL treatment
period; DB+OL treatment periods) on IP will be eligible to continue into a
52-week OLE period on benralizumab 30 mg Q4W (OLE). The OLE is intended to
allow each patient 1 year of treatment with OL benralizumab after completion of
the 52-week DB+OL treatment periods. All eligible patients will be invited to
participate in the OLE. Patients who do not enroll in the OLE will have a
follow-up visit 12 weeks after their last dose of IP.
Intervention
Eligible patients with symptomatic and histologically active EoE before
randomization will be randomized in a 1:1 ratio to receive either 30 mg of
benralizumab or placebo at 4-week intervals for a 24-week treatment period (DB
period). Patients who complete the DB, placebo-controlled treatment period on
investigational product (IP) will continue into an OL treatment period with
benralizumab 30 mg Q4W until Week 52 (OL period). All patients considered
compliant to the protocol and treatment by the Investigator who complete the
52-week treatment period (the 24-week DB treatment period and the 28-week OL
treatment period; DB+OL treatment periods) on IP will be eligible to continue
into a 52-week or longer OLE period on benralizumab 30 mg Q4W (OLE).
Study burden and risks
For the double-Blind treatment period the subject is asked to visit the site at
least 8 times. The visit time will last 1 - 4 hours.
For the Open-label treatment period the subject is asked to visit the site at
least 7 times. The visit time will last 1 - 4 hours.
For the Open-label extension treatment period the subject is asked to visit the
site at least 12 times The visit time will last 1 - 4 hours.
The subject will receive the study medication 13 times in 48 weeks. In case the
subject participates in the extension, the subject will receive study
medication 26 times in 100 weeks. The study medication may cause allergic
reactions. A study physician will supervise the administration of the study
drug and will observe the subject at the study center for 1- 2 hours after each
injection. Additionally, subject may experience side effects of the study
medication.
Blood samples will be taken in this study. The total volume of blood that will
be collected during the first year of the study is 322 ml. In case the subject
continues with the second year of the study there will be an additional 70ml
blood samples taken. As an indication, people who donate blood give 500ml of
blood each time.
The subject will undergo physical examinations at every hospital visit.
The subject will undergo endoscopy including biopsy at least 3 times during the
study. Endoscopies have risks and they can cause discomforts, but the number of
endoscopies is similar as the number of endoscopies in standard practice.
An ECG will be made during 1 visit.
Woman of child bearing potential have to provide a urine sample to test for
pregnancy at screening and each time before administration of study medication
(13 or 26 times).
The subject will be asked to fill out questionnaires at all hospital visits.
The subject must fill out daily, weekly and monthly questionnaires in an
e-Diary. This takes approximately 5 minutes a day.
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
Inclusion criteria
1) Patients 12 to 65 years of age, inclusive, at the time of signing the
informed consent or assent (if applicable) form.
2) Documented previous diagnosis of EoE by endoscopy (documented diagnosis
defined as an esophageal count of >=15 eos/hpf on at least 1 esophageal level)
and confirmed diagnosis by a centrally-read esophageal biopsy for the purposes
of this study (confirmed diagnosis defined as an esophageal count of >=15
eos/hpf at 2 or more esophageal levels). Two to 4 biopsies should be obtained
from both the proximal and distal esophagus. Biopsies can be taken from the
mid-esophagus for additional evaluation.
3) Must be symptomatic at Visit 1 (screening) and Visit 2 :
(a) A patient reported average of at least 2 days per week with an episode of
dysphagia over the 4 weeks prior to the run-in period
AND
(b) At least 2 days with an episode of dysphagia (Daily DSQ >=2) per week
between Visit 1 and the Visit 2 (randomization).
4) Must be adherent to daily diary assessments:
(a) Must complete 70% of daily diaries between Visit 1 and Visit 2; AND
(b) Must have completed at least 8 of 14 daily diaries in the 14 days prior to
randomization.
5) May be on background medications for EoE and related treatments during the
study as long as the background medications have been stable for at least 4
weeks (8 weeks for PPI) prior to screening and there is agreement not to change
type of background medication or dosage for the first 52 weeks of the study
unless medically indicated. If a medication for EoE (including swallowed
steroids, systemic steroids and PPI) is discontinued prior to screening, there
should be a washout period of at least 8 weeks.
6) Negative serum pregnancy test for women of childbearing potential at Visit 1.
7) 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 of IP.
Exclusion criteria
1) Other GI disorders such as active Helicobacter pylori infection, history of
achalasia, esophageal varices, Crohn's disease, ulcerative colitis,
inflammatory bowel disease, or celiac disease.
2) Esophageal stricture that prevents the easy passage of a standard endoscope
or any critical esophageal stricture that requires dilation during the run-in
period.
3) Use of a feeding tube, or not eating solid food daily during the run-in
period.
4) Hypereosinophilic syndrome, defined by multiple organ involvement and
persistent blood eosinophil count >1500 eos/µL.
5) EGPA vasculitis.
6) Eosinophilic gastritis, gastroenteritis, enteritis, or colitis documented by
biopsy.
7) Current malignancy, or history of malignancy with some specific exceptions.
8) History of anaphylaxis to any biologic therapy or vaccine.
9) Current active liver disease:
*Chronic stable hepatitis B and C (including positive testing for hepatitis B
surface antigen [HBsAg] or hepatitis C antibody), or other stable chronic liver
disease are acceptable if patient otherwise meets eligibility criteria.
*Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level >=3
times the upper limit of normal (ULN), confirmed by repeated testing during the
run-in period.
10) Helminth parasitic infection diagnosed within 24 weeks prior to screening
that has not been treated with or has failed to respond to standard of care
therapy.
11) History of known immunodeficiency disorder including a positive human
immunodeficiency virus (HIV) test.
12) use of immunosuppressive medication within 8 weeks prior to screening
13) Initiation or change of a food-elimination diet regimen or reintroduction
of a previously eliminated food group in the 6 weeks prior to start of the
run-in period.
14) Currently pregnant, breastfeeding, or lactating women.
15) Esophageal dilation performed within 8 weeks prior to screening.
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 | EUCTR2019-002871-32-NL |
| ClinicalTrials.gov | NCTvolgt |
| CCMO | NL71639.056.19 |