Inclusion Criteria:
- - The participant is ≥18 years of age (Part 1 only) or 12 to 17 years of age (Part 2
only) at the time of informed consent signing.
Part 2 will enroll adolescent
participants after a planned interim analysis of Part 1 and recommendation to
proceed by the independent DMC.
- - In the opinion of the investigator or subinvestigators, the participant is capable
of understanding and complying with protocol requirements, including completion and
compliance with the electronic diary (ie, completed the diary on at least 11 of the
last 14 days in the 2 weeks prior to Visit 2 [Day -1]).
- - The adult participant signs and dates a written informed consent form (ICF) and any
required privacy authorization prior to the initiation of any study procedures.
For
an adolescent participant, the legally authorized representative (LAR) is willing
and able to complete the informed consent process and comply with study procedures
and visit schedule. The participating adolescent subject will provide assent as
applicable per site guidelines.
- - The participant has the ability to swallow the study drug.
- - The participant has the ability to cooperate with the investigator.
- - The participant has a peak eosinophil count of at least 15 eos/hpf [X 400] from at
least 2 of the 3 esophageal levels on screening endoscopy as measured in at least 6
biopsies, at least 2 each from the proximal, mid, and distal segments of the
esophagus based on central reading.
- - The participant has 4 or more days with dysphagia episodes documented via electronic
diary in the 2 weeks prior to Visit 2 (Day -1).
- - The participant must remain on a stable diet for at least 6 weeks prior to the
Screening Period and is expected to remain on a stable diet during the course of the
study; stable diet is defined as not initiating new elimination diets or
reintroducing previously eliminated foods.
- - A female participant of childbearing potential who is or may be sexually active with
a non-sterilized male partner agrees to routinely use adequate contraception from
the signing of informed consent until 4 weeks after the last dose of study drug.
Exclusion Criteria:
- - The participant is on a pure liquid diet.
- - The participant has documented erosive esophagitis at the screening endoscopy.
- - The participant has other known causes of esophageal eosinophilia or either of the
following conditions: hypereosinophilic syndrome, or eosinophilic granulomatosis
with polyangiitis (Churg-Strauss Syndrome).
- - The participant has a documented diagnosis of eosinophilic gastritis, duodenitis,
jejunitis, ileitis, proctitis, or colitis.
- - The participant has endoscopic Barrett's esophagus (>1 cm of columnar-lined
esophagus) or dysplastic changes in the esophagus.
- - The participant has a history of achalasia, Crohn's disease, ulcerative colitis, or
celiac disease.
- - The participant has a known active Helicobacter pylori infection.
- - The participant has any other clinically significant structural conditions affecting
the esophagus, including: esophageal varices, viral or fungal infection, and history
of radiation therapy, radiofrequency ablation, endoscopic mucosal resection,
cryotherapy to the esophagus, caustic or physiochemical trauma (including
sclerotherapy or esophageal variceal band ligation), or esophageal surgery.
- - The participant has a history of surgery or non-EoE endoscopic intervention, such as
gastric bypass, fundoplication, gastric sleeve, or a history of gastric or duodenal
surgery (except endoscopic removal of benign polyps).
- - The participant has gastric ulcer(s) or duodenal ulcer(s) within 4 weeks before the
first dose of study drug.
- - The participant has had clinically significant upper or lower gastrointestinal
bleeding within 4 weeks prior to the Screening Period.
- - The participant has esophageal stricture(s) unable to be passed with an 8 to 10 mm
endoscope, clinically requires dilation, or has a history of dilation within the 3
months prior to the Screening Period.
- - Use of prescription or non-prescription PPIs within 2 months prior to the Screening
Period.
- - Use of swallowed topical corticosteroid or budesonide oral suspension for EoE within
2 months prior to the Screening Period.
- - Use of systemic corticosteroid for any condition within 3 months prior to the
Screening Period.
- - Use of inhaled or nasal glucocorticoids within 3 months prior to the Screening
Period, except stable dose for at least 3 months prior to the Screening Period for
any condition (should not be changed during the study).
- - Use of dupilumab within 3 months prior to the Screening Period.
- - The participant has received any investigational compound (including those in
post-marketing studies) within 30 days prior to the start of the Screening Period or
vonoprazan in a clinical trial at any time.
A participant who has been screen failed
from another clinical study and who has not been dosed may be considered for
enrollment in this study.
- - The participant has used immunomodulatory therapy within 3 months prior to the
Screening Period or anticipates using immunomodulatory therapy during the study
(except for any ongoing regimen of allergy therapy).
- - The participant is a study site employee, an immediate family member, is in a
dependent relationship with a study site employee who is involved in the conduct of
this study (eg, spouse, parent, child, sibling), or who may have consented under
duress.
- - The participant has a history of hypersensitivity or allergies to vonoprazan
(including the formulation excipients: D-mannitol, microcrystalline cellulose,
hydroxypropyl cellulose, ascorbic acid, fumaric acid, croscarmellose sodium,
magnesium stearate, hypromellose, macrogol 8000, titanium oxide, or red ferric
oxide).
Skin testing may be performed according to local standard practice to
confirm hypersensitivity.
- - The participant has a history of alcohol abuse, illegal drug use, drug addiction or
regularly consumes alcohol within the 12 months prior to the Screening Period (based
on self-report).
Participants must have a negative urine drug screen for
non-prescribed medications at screening. Participants taking prescription drugs will
be allowed. Occasional, recreational use of cannabis is allowed. However,
participants with a cannabis use disorder (eg, frequent use, functional-social
impairment, withdrawal symptoms) per the opinion of the investigator should be
excluded.
- - The participant is taking any excluded medications or treatments listed in the
protocol.
- - If female, the participant is pregnant, lactating, or intending to become pregnant
before, during, or within 4 weeks after participating in this study, or intending to
donate ova during such time period.
- - The participant has a history or clinical manifestations of significant central
nervous system, cardiovascular, pulmonary, metabolic, other gastrointestinal,
urological, endocrine, or hematological disease that, in the opinion of the
investigator, would confound the study results or compromise participant safety.
- - The participant has a history of malignancy (including MALToma) or has been treated
for malignancy within 5 years prior to the start of the Screening Period (Visit 1).
The participant may be included in the study if he/she has recovered from cutaneous
basal cell carcinoma or cervical carcinoma in situ.
- - The participant has acquired immunodeficiency syndrome or human immunodeficiency
virus infection, or tests positive for the hepatitis B surface antigen, hepatitis C
virus (HCV) antibody, or HCV-ribonucleic acid (RNA).
However, participants who test
positive for HCV antibody but negative for HCV-RNA are permitted to participate.
- - The participant has Zollinger-Ellison syndrome or other gastric acid hypersecretory
conditions.
- - The participant requires hospitalization or has surgery scheduled during the course
of the study or has undergone major surgical procedures within 30 days prior to the
Screening Period.
- - The participant has moderate to severe hepatic impairment (Child-Pugh Class B and
Child-Pugh Class C).
- - The participant has severe renal impairment (estimated glomerular filtration rate
<30 mL/min).
- - The participant has any of the following abnormal laboratory test values at the
start of the Screening Period:
1.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 × the
upper limit of normal (ULN) or total bilirubin >2 × ULN (except participants
with Gilbert Syndrome).
2. Creatinine levels:
i .≥18 years of age (adults): >2 mg/dL (>177 μmol/L) ii. 16 to 17 years of age: >1.2
mg/dL (>106 μmol/L) for females and >1.5 mg/dL (>133 μmol/L) for males iii. 12 to 15
years of age: >1.1 mg/dL (>97 μmol/L).
