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Efficacy of Dupilumab on Facilitated Food Introduction in Eosinophilic Esophagitis

Primary Purpose

Eosinophilic Esophagitis

Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Eosinophilic Esophagitis (EoE) food introduction-1st
Eosinophilic Esophagitis (E0E) food introduction-2nd
Eosinophilic Esophagitis (EoE) Food introduction-3rd dose
Dupilumab
Sponsored by
Children's Hospital of Philadelphia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Eosinophilic Esophagitis

Eligibility Criteria

6 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Males or females age 6 to 25 years
  2. 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

  3. History of either milk, egg, soy or wheat induced EoE based on the following criteria in the last two years

    1. Addition of a single food lead to exacerbation of esophageal eosinophilia (increase of greater than 15 eos/hpf) or
    2. Removal of a single food lead to normalization of biopsy (esophageal eosinophilia showed less than 6 eos/hpf) AND
    3. History of either milk, egg, soy or wheat induced EoE based on introduction of the food and symptoms in the last 12 months
  4. Weight > 10 kg
  5. Ability to remain on stable dose of Proton Pump Inhibitor (PPI) therapy throughout the study
  6. Girls > 11 years of age must have a negative urine/serum pregnancy test.
  7. Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria:

  1. Tracheo-esophageal fistulas, inflammatory bowel disease, Barrett's disease, or other significant inflammatory disease of the gastrointestinal tract
  2. Biopsy evidence of eosinophilic infiltration in any other organ system
  3. History of significant esophageal procedures e.g. sclerotherapy or esophagectomy
  4. Systemic immunosuppressant usage in prior 3 months
  5. Narrow caliber esophagus defined as the inability to pass a 9.5 mm endoscopy into the esophagus
  6. IgE mediated reaction to food (milk, egg, soy or wheat) being introduced in the last 12 months
  7. Therapy with biologic molecule (e.g. omalizumab, infliximab) in prior 12 months
  8. Any factors that may pose a significant risk for undergoing anesthesia/sedation
  9. Subjects undergoing any type of immunotherapy to any food (oral immunotherapy, sublingual immunotherapy, specific oral tolerance induction) within 3 months prior to Visit 1.
  10. 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).
  11. Allergy or known hypersensitivity to the dupilumab.
  12. Subjects (or parents of subjects) with obvious excessive anxiety and unlikely to cope with the conditions of an upper Endoscopy and biopsy.
  13. 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).
  14. Participation in another clinical intervention study in the three months prior to Visit 1.
  15. Subjects unable to follow the protocol and the protocol requirements.
  16. Subjects on any experimental drugs or treatments.
  17. Subjects unable to read/understand English or follow the protocol and the protocol requirements.

Sites / Locations

  • Children's Hospital of PhiladelphiaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Study Group

Arm Description

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

Outcomes

Primary Outcome Measures

Esophageal Eosinophilia (number of eosinophils in the esophagus)
Eosinophils per high power field on esophageal biopsy
Esophageal Eosinophilia (number of eosinophils in the esophagus)
Eosinophils per high power field on esophageal biopsy
Esophageal Eosinophilia (number of eosinophils in the esophagus)
Eosinophils per high power field on esophageal biopsy

Secondary Outcome Measures

Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
Min 0-Max-100, lower is better
Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
Min 0-Max-100, lower is better
Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
Min 0-Max-100, lower is better

Full Information

First Posted
December 21, 2021
Last Updated
January 27, 2023
Sponsor
Children's Hospital of Philadelphia
Collaborators
Regeneron Pharmaceuticals, Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT05247866
Brief Title
Efficacy of Dupilumab on Facilitated Food Introduction in Eosinophilic Esophagitis
Official Title
Efficacy of Dupilumab on Facilitated Food Introduction in Eosinophilic Esophagitis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 16, 2022 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Philadelphia
Collaborators
Regeneron Pharmaceuticals, Genzyme, a Sanofi Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eosinophilic Esophagitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
All patients receive active therapy
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Study Group
Arm Type
Experimental
Arm Description
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
Intervention Type
Dietary Supplement
Intervention Name(s)
Eosinophilic Esophagitis (EoE) food introduction-1st
Intervention Description
1 serving size of food proven to induce histologic and clinical symptoms in EoE
Intervention Type
Dietary Supplement
Intervention Name(s)
Eosinophilic Esophagitis (E0E) food introduction-2nd
Intervention Description
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
Intervention Type
Dietary Supplement
Intervention Name(s)
Eosinophilic Esophagitis (EoE) Food introduction-3rd dose
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Dupilumab
Intervention Description
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
Primary Outcome Measure Information:
Title
Esophageal Eosinophilia (number of eosinophils in the esophagus)
Description
Eosinophils per high power field on esophageal biopsy
Time Frame
week 24
Title
Esophageal Eosinophilia (number of eosinophils in the esophagus)
Description
Eosinophils per high power field on esophageal biopsy
Time Frame
week 36
Title
Esophageal Eosinophilia (number of eosinophils in the esophagus)
Description
Eosinophils per high power field on esophageal biopsy
Time Frame
week 48
Secondary Outcome Measure Information:
Title
Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
Description
Min 0-Max-100, lower is better
Time Frame
week 24
Title
Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
Description
Min 0-Max-100, lower is better
Time Frame
week 36
Title
Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
Description
Min 0-Max-100, lower is better
Time Frame
week 48
Other Pre-specified Outcome Measures:
Title
Rate of Maintenance of Remission (less than <6 eos/hpf) in esophageal biopsy
Description
Less than 6 eosinophils per high power field in peak count in esophageal biopsy
Time Frame
week 24
Title
Rate of Maintenance of Remission (less than <6 eos/hpf) in esophageal biopsy
Description
Less than 6 eosinophils per high power field in peak count in esophageal biopsy
Time Frame
week 36
Title
Rate of Maintenance of Remission (less than <6 eos/hpf) in esophageal biopsy
Description
Less than 6 eosinophils per high power field in peak count in esophageal biopsy
Time Frame
week 48
Title
Rate of Maintenance of remission (less than <15 eos/hpf) in esophageal biopsy
Description
Less than 15 eosinophils per high power field in peak count in esophageal biopsy
Time Frame
Week 24
Title
Rate of Maintenance of remission (less than <15 eos/hpf) in esophageal biopsy
Description
Less than 15 eosinophils per high power field in peak count in esophageal biopsy
Time Frame
Week 36
Title
Rate of Maintenance of remission (less than <15 eos/hpf) in esophageal biopsy
Description
Less than15 eosinophils per high power field in peak count in esophageal biopsy
Time Frame
Week 48
Title
Change in endoscopic Scoring system (EREFS)
Description
Changes from baseline from upper endoscopy validated score (0-10), lower is better
Time Frame
week 24
Title
Change in endoscopic Scoring system (EREFS)
Description
Changes from baseline from upper endoscopy validated score (0-10), lower is better
Time Frame
week 36
Title
Change in endoscopic Scoring system (EREFS)
Description
Changes from baseline from upper endoscopy validated score (0-10), lower is better
Time Frame
week 48
Title
Changes in EoE Quality of life from baseline
Description
Changes from baseline in EoE specific Health related Quality of Life (range 0-96), higher is worse
Time Frame
week 24
Title
Changes in EoE Quality of life from baseline
Description
Changes from baseline in EoE Health related Quality of Life (range 0-96), higher is worse
Time Frame
week 36
Title
Changes in EoE Quality of life from baseline
Description
Changes from baseline in EoE Health related Quality of Life (range 0-96), higher is worse
Time Frame
week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sharon Carbonara
Phone
2155902549
Email
carbonara@chop.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Spergel, MD, PhD
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Danielle Williams
Email
WilliamsDS@chop.edu
First Name & Middle Initial & Last Name & Degree
Jonathan M Spergel, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
After the study is completed and published, we will share the study protocol and limited deidentified data.
IPD Sharing Time Frame
The data will be released after the data is published.

Learn more about this trial

Efficacy of Dupilumab on Facilitated Food Introduction in Eosinophilic Esophagitis

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