a4b7 Integrin in Eosinophilic Esophagitis



Status:Completed
Conditions:Gastrointestinal
Therapuetic Areas:Gastroenterology
Healthy:No
Age Range:18 - Any
Updated:2/23/2019
Start Date:March 2016
End Date:December 31, 2018

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Investigating the Role of a4b7 Integrin as a Therapeutic Target in Eosinophilic Esophagitis

The overall objective of this preclinical study is to further the investigators mechanistic
understanding of the role that the α4β7 and mucosal addressin cell adhesion molecule
(MAdCAM-1) pathway plays in mediating eosinophil recruitment in EoE. To accomplish this, the
investigators aim to (1) determine the baseline and dynamic patterns of α4β7 integrin
expression on circulating and tissue eosinophils in EoE and in the setting of non-EoE
esophageal eosinophilia (e.g., reflux esophagitis) and (2) determine the complete profile of
eosinophil integrin molecules that may play a role in active EoE.


Inclusion Criteria:

1. Able to give written informed consent

2. Male or female patients aged 18-65 years at time of screening

3. Confirmed active EoE at screening or within 8 weeks prior to baseline visit, as
defined by esophageal mucosal eosinophils ≥15 per high power field (HPF, 400X
magnification) despite at least 4 weeks of proton pump inhibitor (PPI) therapy with
omeprazole 20 mg twice daily or the equivalent. updated 14APR2015 Page 8 of 19

4. Within the week prior to dosing, patient has one of the following symptoms of
moderate, or worse, severity: dysphagia, vomiting, regurgitation, abdominal pain,
chest pain/heartburn.

5. Maintained on a stabilized diet for at least 6 weeks prior to screening and during the
course of the study; stable diet is defined as no initiation of single or multiple
elimination diets or reintroduction of previously eliminated food groups.

6. Willing and able to comply with all clinic visits and study-related procedures

7. Able to understand and complete study-related questionnaires

Exclusion Criteria:

1. Another disorder that causes esophageal eosinophilia (e.g., hypereosinophilic
syndrome, Churg-Strauss, parasitic infection)

2. History of abnormal gastric or duodenal biopsy or documented GI disorders other than
EoE (e.g., celiac disease, Crohn's disease or H. pylori infection)

3. History of the following GI surgeries: fundoplication, gastric surgery or surgery for
esophageal atresia

4. Use of systemic immunosuppressive or immunomodulating agents (oral prednisone,
anti-immunoglobulin E (IgE) monoclonal antibody (mAb), methotrexate, cyclosporine,
INFα, or anti-TNF) within six months prior to study entry.

5. A stricture on endoscopy that prevents passage of the endoscope

6. Participation in any investigational drug or device study within 30 days prior to
study entry.

7. Female subjects who are pregnant or nursing.

8. Chronic infections such as HIV, hepatitis B or C, active mycobacterial (TB) or fungal
infections.

9. Neoplasm or a history of malignancy in the preceding 5 years.

10. Concurrent infection or disease that may preclude assessment of eosinophilic
esophagitis.
We found this trial at
1
site
185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: John J Garber, MD
Phone: 617-643-2950
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mi
from
Boston, MA
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