Mepo for EoE Study

This is a multi-center, randomized, double blind, parallel-arm, placebo controlled trial of
mepolizumab. After the first 3 month blinded phase, there will be a second 3 month blinded
phase where all patients receive active medication, but the dose will be lower in the
subjects initially randomized to the placebo arm.

In the first arm, subjects will receive mepolizumab 300 mg SQ monthly for 3 months. In the
second arm, subjects will receive a placebo SQ injection monthly for 3 months. Both groups
will have the injection administered under direct observation in a Clinical & Translational
Research Center (CTRC) or other clinic to ensure proper administration and compliance. Each
visit will also provide an opportunity for symptom questionnaires to be completed and for
blood samples to be drawn. After 3 months (the time point where the primary outcome is
assessed), all subjects initially randomized to active treatment will continue with
mepolizumab dosing 300 mg SQ monthly, and will remain blinded. All subjects initially
randomized to placebo will receive mepolizumab 100mg SQ monthly, and will remain blinded. Of
note, no dietary changes, changes in baseline Proton Pump Inhibitor (PPI) medication dose,
changes in inhaled or intranasal steroid doses, or administration or oral, topical/swallowed,
or systemic steroids will be allowed during the study period. Subjects will undergo endoscopy
after the first blinded phase (at 3 months) and after the second blinded phase (after 6
months).

Inclusion Criteria:

1. Age 16-75

2. Diagnosis of EoE as per consensus guidelines (including PPI non-response). PPI
non-response is defined as >15 EOS/hpf after 8 weeks of high dose administration (40mg
total per day or higher) of any approved PPI medication.

3. Active eosinophilia on esophageal biopsy, with a peak count of least 15 EOS/hpf from
at least one esophageal level.

4. Biopsies from the stomach and duodenum that have ruled out alternative etiologies in
all children and in adults with abnormal endoscopic findings or when other gastric or
small intestinal conditions are clinical possibilities. If these samples have been
obtained during a previous endoscopic evaluation and in the judgement of the
investigator the patient has not had a clinically significant change that would merit
repeat gastric/duodenal biopsies, then prior normal gastric and duodenal biopsies are
acceptable to exclude alternate etiologies.

5. Active symptoms of dysphagia with more than 3 episodes of dysphagia over a period of 2
weeks during the screening period, and an Eosinophilic Esophagitis Symptom Activity
Index (EEsAI; see below for details) score of ≥ 27 at baseline.

6. Able to read, comprehend, and sign consent form.

7. Have maintained a stable diet for 6 weeks prior to enrollment.

8. Able to maintain a stable diet throughout the duration of the study period.

9. Female subjects of childbearing potential who have had their first menses agree to use
a highly effective method of birth control during the study and for 30 days after the
last dose of study drug. Female subjects with reproductive potential who are using
systemic contraceptives (e.g., oral contraceptives, injectable contraceptives,
implantable/insertable hormonal contraceptive products, or transdermal patches) to
prevent pregnancy must have stable use for ≥28 days prior to screening. See section
5.3 for additional details.

Exclusion Criteria:

1. Esophageal dilation within 8 weeks of the screening endoscopy.

2. Inability to pass a standard upper endoscope (8-10mm) due to esophageal narrowing or
stricturing.

3. Swallowed/topical steroids for EoE within 4 weeks of the screening endoscopy, or
systemic corticosteroids within 8 weeks of the screening endoscopy.

4. Not having maintained a stable diet for at least 6 weeks preceding enrollment.

5. Initiation, discontinuation, or change of dose regimen of PPIs; leukotriene
inhibitors; or nasal, inhaled, and/or orally administered topical corticosteroids for
any condition (such as gastroesophageal reflux disease, asthma, or allergic rhinitis)
within the 8 weeks prior to the qualifying esophagogastroduodenoscopy (EGD).

6. Active parasitic infections.

7. Pregnancy.

8. Women of children bearing potential who are not on highly-effective contraception.

9. Active infections judged at the discretion of the investigator.