Efficacy of Dupilumab on Facilitated Food Introduction in Eosinophilic Esophagitis

Study Overview
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Brief Summary
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Eosinophilic Esophagitis (EoE) is a food driven non-immunoglobulin E (IgE) mediated disease involving eosinophils and type 2 inflammation. Current therapies include diet and the off label use of medications including proton pump inhibitors, topical steroids or biologics. Food elimination creates a decrease quality of life in many children. The goal of the study is to examine a T2 inhibitor (dupilumab) can allow successful reintroduction of allergic EoE foods into the diet. This is a single site study, enrolling subjects 6 to 25 years of age.

Detailed Description
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This study is an open label exploratory study to examine if patients controlled with dupilumab can successful introduce EoE trigger foods back into their diet. This is a single site study, enrolling subjects 6 to 25 years of age. In the initial 12 week period, patients will be start on dupilumab on the doses used in the phase 3 trials to control disease. If disease is controlled based on histologic and symptom control at week 12 endoscopy, patients will be start on EoE trigger food. The trigger foods will be based on both a combination of history and histology results. The food will have trigger EoE by histology in the last 2 years and symptoms in the last year when reintroduced into the diet. The study will focus on the the four most common foods that trigger EoE: milk, egg, wheat and soy. For the initial food introduction, the subjects will add one serving size of the food daily for 12 weeks. After 12 weeks, the subjects will have a 2nd endoscopy if the 2nd endoscopy is normal, the subjects will increase the trigger food to 2 serving sizes a day or add an additional trigger food. A 3rd endoscopy will be done if the patients increases the food amount or adds a new food at week 36 (12 weeks after adding the new food). If the subject does not increase or add new foods at week 24, the 3rd endoscopy will not be obtained. All subjects will have end of study endoscopy at week 48. If the subjects have abnormal endoscopy or increase in symptoms, the amount food will be reduced by 50% and repeat endoscopy will be obtained at the same time schedule-12 weeks later.

Official Title
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Efficacy of Dupilumab on Facilitated Food Introduction in Eosinophilic Esophagitis

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Dietary Supplement: Eosinophilic Esophagitis (EoE) food introduction-1st
* Dietary Supplement: Eosinophilic Esophagitis (E0E) food introduction-2nd
* Dietary Supplement: Eosinophilic Esophagitis (EoE) Food introduction-3rd dose
* Drug: Dupilumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females age 6 to 25 years Diagnosis of Eosinophilic Esophagitis based on the most recent international consensus definition (Dellon et al, Gastroenterology 2019) a) History of endoscopy with a peak count of >15 eosinophils per high powered field meeting consensus criteria for Eosinophilic Esophagitis1 History of either milk, egg, soy or wheat induced EoE based on the following criteria in the last two years Addition of a single food lead to exacerbation of esophageal eosinophilia (increase of greater than 15 eos/hpf) or Removal of a single food lead to normalization of biopsy (esophageal eosinophilia showed less than 6 eos/hpf) AND History of either milk, egg, soy or wheat induced EoE based on introduction of the food and symptoms in the last 12 months Weight > 10 kg Ability to remain on stable dose of Proton Pump Inhibitor (PPI) therapy throughout the study Girls > 11 years of age must have a negative urine/serum pregnancy test. Parental/guardian permission (informed consent) and if appropriate, child assent. Exclusion Criteria: Tracheo-esophageal fistulas, inflammatory bowel disease, Barrett's disease, or other significant inflammatory disease of the gastrointestinal tract Biopsy evidence of eosinophilic infiltration in any other organ system History of significant esophageal procedures e.g. sclerotherapy or esophagectomy Systemic immunosuppressant usage in prior 3 months Narrow caliber esophagus defined as the inability to pass a 9.5 mm endoscopy into the esophagus IgE mediated reaction to food (milk, egg, soy or wheat) being introduced in the last 12 months Therapy with biologic molecule (e.g. omalizumab, infliximab) in prior 12 months Any factors that may pose a significant risk for undergoing anesthesia/sedation Subjects undergoing any type of immunotherapy to any food (oral immunotherapy, sublingual immunotherapy, specific oral tolerance induction) within 3 months prior to Visit 1. Active IgE- mediated milk, egg, wheat or soy allergy based on skin test or history (if those foods are being introduced back into the diet). Allergy or known hypersensitivity to the dupilumab. Subjects (or parents of subjects) with obvious excessive anxiety and unlikely to cope with the conditions of an upper Endoscopy and biopsy. Past or current disease(s), which in the opinion of the Investigator or the Sponsor, may affect the subject's participation in this study, including but not limited to active autoimmune disorders, immunodeficiency, malignancy, uncontrolled diseases (hypertension, psychiatric (especially anxiety), cardiac), or other disorders (e.g., liver, gastrointestinal, kidney, cardiovascular, pulmonary disease, or blood disorders). Participation in another clinical intervention study in the three months prior to Visit 1. Subjects unable to follow the protocol and the protocol requirements. Subjects on any experimental drugs or treatments. Subjects unable to read/understand English or follow the protocol and the protocol requirements.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All patients receive active therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>30 patients will be given dupilumab (dose based on current approved doses or used in current EoE clinical trial, q weekly dosing) and monitored for clinical response after 12 weeks of therapy) Dosing: >12 years of age > 40 kg 300 SQ weekly 30- 40 kg 300 mg SQ Q2 weeks 15-29.9 kg 200 mg SQ Q2 weeks 6-11 years of age 5-15 kg 100 mg SQ Q2W 15-30 kg 200 mg SQ Q2W >30-60 kg 300 mg SQ Q2W | Dietary Supplement: Eosinophilic Esophagitis (EoE) food introduction-1st<br>* 1 serving size of food proven to induce histologic and clinical symptoms in EoE<br>Dietary Supplement: Eosinophilic Esophagitis (E0E) food introduction-2nd<br>* Either 1 serving size of different food (not food in arm 1) to induce histologic and clinical symptoms in EoE or Increase the food in arm 1 to 2 serving size a day<br>Dietary Supplement: Eosinophilic Esophagitis (EoE) Food introduction-3rd dose<br>* Either 1 serving size of different food (not food in arm 1 or 2) to induce histologic and clinical symptoms in EoE or Increase the food in arm 2 to 2 serving size a day or unlimited amounts of food arm 1<br>Drug: Dupilumab<br>* All patients will receive open label dupilumab at the following doses >12 years of age > 40 kg 300 subcutaneous (SQ) weekly 6-11 years of age 5-15 kg 100 mg SQ every 2 weeks (Q2W) 15-30 kg 200 mg SQ Q2W >30-60 kg 300 mg SQ Q2W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Esophageal Eosinophilia (number of eosinophils in the esophagus) | Eosinophils per high power field on esophageal biopsy | week 24 | 
| Esophageal Eosinophilia (number of eosinophils in the esophagus) | Eosinophils per high power field on esophageal biopsy | week 36 | 
| Esophageal Eosinophilia (number of eosinophils in the esophagus) | Eosinophils per high power field on esophageal biopsy | week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score) | Min 0-Max-100, lower is better | week 24 | 
| Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score) | Min 0-Max-100, lower is better | week 36 | 
| Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score) | Min 0-Max-100, lower is better | week 48 |