Informed consent or assent (if applicable)
1 Provision of signed and dated, written informed consent form or assent form (if
applicable) prior to any mandatory study specific procedures, sampling, and analyses.
2 Provision of signed and dated written Genetic informed consent prior to collection of
sample for genetic analysis for adult patients.
The Informed Consent Form (ICF)/assent form process is described in Appendix A-3.
Age
3 Patients 12 to 65 years of age, inclusive, at the time of signing the informed consent or
assent (if applicable) form.
Type of patient and disease characteristics
4 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.
5 Must be symptomatic at Visit 1 (run-in period) and Visit 2 (randomization):
(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)
6 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
7 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 prior to the
run-in period and there is agreement not to change type of background medication or
dosage for the first 52 weeks of the study unless medically indicated. Patients on PPI
therapy must report a stable dose for at least 8 weeks prior to the run-in period. See
Section 6.5.1 for details regarding background medications.
Weight
8 Body weight of at least 35 kg.
Reproduction
9 Negative serum pregnancy test for female patients of childbearing potential at Visit 1
(enrollment).
10 Women of childbearing potential (WOCBP) must agree to use a highly effective form of
birth control (confirmed by the Investigator) from randomization throughout the study
duration and within 16 weeks after last dose if IP. A highly effective method of
contraception is defined as one that can achieve a failure rate of less than 1% per year
when used consistently and correctly. Highly effective forms of birth control include:
(a) Combined (estrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation- oral, intravaginal, or transdermal
(b) Progestogen-only hormonal contraception associated with inhibition of ovulationoral,
injectable, or implantable
(c) Intrauterine device (IUD)
(d) Intrauterine hormone-releasing system (IUS)
(e) Bilateral tubal occlusion
(f) Sexual abstinence, i.e. refraining from heterosexual intercourse (The reliability of
sexual abstinence needs to be evaluated in relation to the duration of the clinical
study and the preferred and usual lifestyle of the patient.)
(g) Vasectomized sexual partner (provided that partner is the sole sexual partner of the
WOCBP study patient and that the vasectomized partner has received medical
assessment of the surgical success)
11 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 randomization without an
alternative medical cause. The following age-specific requirements apply:
Women <50 years old will 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.
Until FSH is documented to be within menopausal range, treat the patient as
WOCBP.
Women ≥50 years old will be considered postmenopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatment.
5.2 Exclusion criteria
Medical conditions
1 As judged by the Investigator, any evidence of a medical illness which in the
Investigator’s opinion makes it undesirable for the patient to participate in the study.
2 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.
3 Any clinical significant abnormal findings in physical examination, vital signs,
hematology, clinical chemistry, or urinalysis during run-in period, which in the opinion of
the Investigator, may put the patient at risk, because of his/her participation in the study,
or may influence the results of the study, or the patients’ ability to complete entire
duration of the study.
4 Esophageal stricture that prevents the easy passage of a standard endoscope or any critical
esophageal stricture that requires dilation during the run-in period.
5 Use of a feeding tube, or not eating solid food daily during the run-in period.
6 Hypereosinophilic syndrome, defined by multiple organ involvement and persistent blood
eosinophil count >1500 eos/μL.
7 EGPA vasculitis.
8 Eosinophilic gastritis, gastroenteritis, enteritis, or colitis documented by biopsy.
9 Current malignancy, or history of malignancy, except for:
10 Patients 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 patient is in
remission and curative therapy was completed at least 12 months prior to the date
informed consent, and assent when applicable was obtained.
11 Patients who have had other malignancies are eligible provided that the patient is in
remission and curative therapy was completed at least 5 years prior to the date informed
consent, and assent when applicable, was obtained.
12 History of anaphylaxis to any biologic therapy or vaccine.
13 Current active liver disease:
14 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. Stable chronic liver disease should generally
be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia,
esophageal or gastric varices, or persistent jaundice, or cirrhosis.
15 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.
Transient increase of AST/ALT level that resolves by the time of randomization is
acceptable if in the Investigator’s opinion the patient does not have an active liver disease
and meets other eligibility criteria.
16 Helminth parasitic infection diagnosed within 24 weeks prior to the date informed
consent or assent (if applicable) is obtained that has not been treated with or has failed to
respond to standard of care therapy.
17 History of known immunodeficiency disorder including a positive human
immunodeficiency virus (HIV) test.
Prior/concomitant therapy
18 Concomitant use of immunosuppressive medication (including but not limited to:
methotrexate, troleandomycin, cyclosporine, azathioprine, and systemic corticosteroids
(see Table 9).
19 Receipt of immunoglobulin or blood products within 30 days prior to the date informed
consent or assent (if applicable) is obtained.
20 Receipt of live attenuated vaccines 30 days prior to date of informed consent or assent (if
applicable).
21 Receipt of any marketed or investigational biologic (monoclonal or polyclonal antibody)
within 4 months or 5 half-lives prior to the date informed consent or assent (if applicable),
is obtained, whichever is longer, and during the study period.
Prior/concurrent clinical study experience
22 Previous participation in a benralizumab clinical study.
23 Known history of allergy or reaction to any component of the IP formulation.
24 Receipt of any investigational drug within 30 days or 5 half-lives prior to randomization,
whichever is longer.
Other exclusions
25 Initiation or change of a food-elimination diet regimen or re-introduction of a previously
eliminated food group in the 6 weeks prior to start of the run-in period.
26 For women only: Currently pregnant, breastfeeding, or lactating women.
27 A serum pregnancy test will be done for women of childbearing potential at screening and
a urine pregnancy test must be performed for women of childbearing potential at each
treatment visit prior to IP administration. A positive urine test result must be confirmed
with a serum pregnancy test. If serum test is positive, the patient should be excluded.