Eosinophilic Esophagitis
Conditions
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.
Interventions
DIETARY_SUPPLEMENTEosinophilic Esophagitis (EoE) food introduction-1st
1 serving size of food proven to induce histologic and clinical symptoms in EoE
DIETARY_SUPPLEMENTEosinophilic Esophagitis (E0E) food introduction-2nd
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
DIETARY_SUPPLEMENTEosinophilic Esophagitis (EoE) Food introduction-3rd dose
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
DRUGDupilumab
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
Sponsors
Regeneron Pharmaceuticals
Genzyme, a Sanofi Company
Children's Hospital of Philadelphia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All patients receive active therapy
Eligibility
Sex/Gender
ALL
Age
6 Years to 25 Years
Healthy volunteers
No
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. 18. Subjects unable to read/understand English or follow the protocol and the protocol requirements. 19. Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit or throughout the trial 20. Major elective surgeries are prohibited during the study 21. Female patients who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study 22. Women of children bearing potential (WOCBP) who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 12 weeks after the last dose. This includes female patients who experience menarche during the study duration and who are unwilling to follow the precautions for WOCBP. 23. Chronic or acute infection requiring treatment with systemic antibiotic, antivirals, or antifungal within 2 weeks of baseline visits a. Patients maybe rescreened after infection resolves 24. Participants with active or suspected parasitic infection are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Esophageal Eosinophilia (Number of Eosinophils in the Esophagus) | week 24 | Eosinophils per high power field on esophageal biopsy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pediatric Eosinophilic Esophagitis Symptom Score (Total Score Based on Pediatric Symptom Score) | week 24 | Min 0-Max-100, lower is better |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate of Maintenance of Remission (Less Than <6 Eos/Hpf) in Esophageal Biopsy | week 24 | Less than 6 eosinophils per high power field in peak count in esophageal biopsy |
| Rate of Maintenance of Remission (Less Than <15 Eos/Hpf) in Esophageal Biopsy | Week 24 | Less than 15 eosinophils per high power field in peak count in esophageal biopsy |
| Change in Endoscopic Scoring System (EREFS) | week 24 | Changes from baseline from upper endoscopy validated score (0-10), lower is better |
| Changes in EoE Quality of Life From Baseline | week 24 | Changes from baseline in EoE specific Health related Quality of Life (range 0-96), higher is worse |
Countries
United States
Participant flow
Recruitment details
21 patients recruited
Pre-assignment details
Open label study, all assigned dupilumab
Participants by arm
| Arm | Count |
|---|---|
| Study Group 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 | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Study Group |
|---|---|
| Age, Categorical <=18 years | 21 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Atopy | 19 Count of Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 10 / 21 |
| serious Total, serious adverse events | 1 / 21 |
Outcome results
Primary
Esophageal Eosinophilia (Number of Eosinophils in the Esophagus)
Eosinophils per high power field on esophageal biopsy
Time frame: week 24
Population: 5 patients dropped out to subject withrdraw and anxiety due to injections before completing this endpoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Esophageal Eosinophilia (Number of Eosinophils in the Esophagus) | 5.3 eosinophils/high power field | Standard Deviation 8.9 |
Primary
Esophageal Eosinophilia (Number of Eosinophils in the Esophagus)
Eosinophils per high power field on esophageal biopsy
Time frame: week 48
Population: 2 patients dropped before this time point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Esophageal Eosinophilia (Number of Eosinophils in the Esophagus) | 2.6 eosinophils per high power field | Standard Deviation 4.5 |
Primary
Esophageal Eosinophilia (Number of Eosinophils in the Esophagus)
Eosinophils per high power field on esophageal biopsy
Time frame: week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Esophageal Eosinophilia (Number of Eosinophils in the Esophagus) | 1.3 eosinophils/high power field | Standard Deviation 2.8 |
Secondary
Pediatric Eosinophilic Esophagitis Symptom Score (Total Score Based on Pediatric Symptom Score)
Min 0-Max-100, lower is better
Time frame: week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Pediatric Eosinophilic Esophagitis Symptom Score (Total Score Based on Pediatric Symptom Score) | 7.7 units on a scale | Standard Deviation 7.7 |
Secondary
Pediatric Eosinophilic Esophagitis Symptom Score (Total Score Based on Pediatric Symptom Score)
Min 0-Max-100, lower is better
Time frame: week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Pediatric Eosinophilic Esophagitis Symptom Score (Total Score Based on Pediatric Symptom Score) | 5.1 units on a scale | Standard Deviation 6.4 |
Secondary
Pediatric Eosinophilic Esophagitis Symptom Score (Total Score Based on Pediatric Symptom Score)
Min 0-Max-100, lower is better
Time frame: week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Pediatric Eosinophilic Esophagitis Symptom Score (Total Score Based on Pediatric Symptom Score) | 8 units on a scale | Standard Deviation 11.3 |
Other Pre-specified
Change in Endoscopic Scoring System (EREFS)
Changes from baseline from upper endoscopy validated score (0-10), lower is better
Time frame: week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Change in Endoscopic Scoring System (EREFS) | 0.4 units on a scale | Standard Deviation 0.7 |
Other Pre-specified
Change in Endoscopic Scoring System (EREFS)
Changes from baseline from upper endoscopy validated score (0-10), lower is better
Time frame: week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Change in Endoscopic Scoring System (EREFS) | 0.2 units on a scale | Standard Deviation 0.4 |
Other Pre-specified
Change in Endoscopic Scoring System (EREFS)
Changes from baseline from upper endoscopy validated score (0-10), lower is better
Time frame: week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Change in Endoscopic Scoring System (EREFS) | 0.6 units on a scale | Standard Deviation 0.9 |
Other Pre-specified
Changes in EoE Quality of Life From Baseline
Changes from baseline in EoE Health related Quality of Life (range 0-96), higher is worse
Time frame: week 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Changes in EoE Quality of Life From Baseline | 8 units on a scale | Standard Deviation 11.31 |
Other Pre-specified
Changes in EoE Quality of Life From Baseline
Changes from baseline in EoE specific Health related Quality of Life (range 0-96), higher is worse
Time frame: week 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Changes in EoE Quality of Life From Baseline | 7.06 units on a scale | Standard Deviation 6.84 |
Other Pre-specified
Changes in EoE Quality of Life From Baseline
Changes from baseline in EoE Health related Quality of Life (range 0-96), higher is worse
Time frame: week 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Changes in EoE Quality of Life From Baseline | 5.14 units on a scale | Standard Deviation 6.44 |
Other Pre-specified
Rate of Maintenance of Remission (Less Than <15 Eos/Hpf) in Esophageal Biopsy
Less than 15 eosinophils per high power field in peak count in esophageal biopsy
Time frame: Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Rate of Maintenance of Remission (Less Than <15 Eos/Hpf) in Esophageal Biopsy | 14 Participants |
Other Pre-specified
Rate of Maintenance of Remission (Less Than <15 Eos/Hpf) in Esophageal Biopsy
Less than 15 eosinophils per high power field in peak count in esophageal biopsy
Time frame: Week 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Rate of Maintenance of Remission (Less Than <15 Eos/Hpf) in Esophageal Biopsy | 13 Participants |
Other Pre-specified
Rate of Maintenance of Remission (Less Than <15 Eos/Hpf) in Esophageal Biopsy
Less than15 eosinophils per high power field in peak count in esophageal biopsy
Time frame: Week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Rate of Maintenance of Remission (Less Than <15 Eos/Hpf) in Esophageal Biopsy | 13 Participants |
Other Pre-specified
Rate of Maintenance of Remission (Less Than <6 Eos/Hpf) in Esophageal Biopsy
Less than 6 eosinophils per high power field in peak count in esophageal biopsy
Time frame: week 48
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Rate of Maintenance of Remission (Less Than <6 Eos/Hpf) in Esophageal Biopsy | 11 Participants |
Other Pre-specified
Rate of Maintenance of Remission (Less Than <6 Eos/Hpf) in Esophageal Biopsy
Less than 6 eosinophils per high power field in peak count in esophageal biopsy
Time frame: week 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Rate of Maintenance of Remission (Less Than <6 Eos/Hpf) in Esophageal Biopsy | 13 Participants |
Other Pre-specified
Rate of Maintenance of Remission (Less Than <6 Eos/Hpf) in Esophageal Biopsy
Less than 6 eosinophils per high power field in peak count in esophageal biopsy
Time frame: week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study Group | Rate of Maintenance of Remission (Less Than <6 Eos/Hpf) in Esophageal Biopsy | 12 Participants |