Clinical trial NCT05247866: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Eosinophilic Esophagitis
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
name: Genzyme, a Sanofi Company
First posted: 2022-02-21
Enrollment: 21
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All patients receive active therapy
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Esophageal Eosinophilia (number of eosinophils in the esophagus)
timeFrame: week 24
measure: Esophageal Eosinophilia (number of eosinophils in the esophagus)
timeFrame: week 36
measure: Esophageal Eosinophilia (number of eosinophils in the esophagus)
timeFrame: week 48
Secondary outcomes:
measure: Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
timeFrame: week 24
measure: Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
timeFrame: week 36
measure: Pediatric Eosinophilic Esophagitis Symptom Score (total score based on pediatric symptom score)
timeFrame: week 48
Other outcomes:
measure: Rate of Maintenance of Remission (less than <6 eos/hpf) in esophageal biopsy
timeFrame: week 24
measure: Rate of Maintenance of Remission (less than <6 eos/hpf) in esophageal biopsy
timeFrame: week 36
measure: Rate of Maintenance of Remission (less than <6 eos/hpf) in esophageal biopsy
timeFrame: week 48
measure: Rate of Maintenance of remission (less than <15 eos/hpf) in esophageal biopsy
timeFrame: Week 24
measure: Rate of Maintenance of remission (less than <15 eos/hpf) in esophageal biopsy
timeFrame: Week 36
measure: Rate of Maintenance of remission (less than <15 eos/hpf) in esophageal biopsy
timeFrame: Week 48
measure: Change in endoscopic Scoring system (EREFS)
timeFrame: week 24
measure: Change in endoscopic Scoring system (EREFS)
timeFrame: week 36
measure: Change in endoscopic Scoring system (EREFS)
timeFrame: week 48
measure: Changes in EoE Quality of life from baseline
timeFrame: week 24
measure: Changes in EoE Quality of life from baseline
timeFrame: week 36
measure: Changes in EoE Quality of life from baseline
timeFrame: week 48
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Jonathan Spergel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rothenberg ME, Dellon ES, Collins MH, Hirano I, Chehade M, Bredenoord AJ, Lucendo AJ, Spergel JM, Sun X, Hamilton JD, Mortensen E, Laws E, Maloney J, Mannent LP, McCann E, Liu X, Glotfelty L, Shabbir A. Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2023 Nov;8(11):990-1004. doi: 10.1016/S2468-1253(23)00204-2. Epub 2023 Aug 31.
citation: McCann E, Chehade M, Spergel JM, Yaworsky A, Symonds T, Stokes J, Tilton ST, Sun X, Kamat S. Validation of the novel Eosinophilic Esophagitis Impact Questionnaire. J Patient Rep Outcomes. 2023 Nov 27;7(1):120. doi: 10.1186/s41687-023-00654-z.
citation: Dellon ES, Rothenberg ME, Collins MH, Hirano I, Chehade M, Bredenoord AJ, Lucendo AJ, Spergel JM, Aceves S, Sun X, Kosloski MP, Kamal MA, Hamilton JD, Beazley B, McCann E, Patel K, Mannent LP, Laws E, Akinlade B, Amin N, Lim WK, Wipperman MF, Ruddy M, Patel N, Weinreich DR, Yancopoulos GD, Shumel B, Maloney J, Giannelou A, Shabbir A. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. N Engl J Med. 2022 Dec 22;387(25):2317-2330. doi: 10.1056/NEJMoa2205982.
citation: Spergel BL, Ruffner MA, Godwin BC, Liacouras CA, Cianferoni A, Gober L, Hill DA, Brown-Whitehorn TF, Chaiboonma K, Aceves SA, Muir AM, Spergel JM. Improvement in eosinophilic esophagitis when using dupilumab for other indications or compassionate use. Ann Allergy Asthma Immunol. 2022 May;128(5):589-593. doi: 10.1016/j.anai.2022.01.019. Epub 2022 Jan 25.
citation: Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, Spechler SJ, Attwood SE, Straumann A, Aceves SS, Alexander JA, Atkins D, Arva NC, Blanchard C, Bonis PA, Book WM, Capocelli KE, Chehade M, Cheng E, Collins MH, Davis CM, Dias JA, Di Lorenzo C, Dohil R, Dupont C, Falk GW, Ferreira CT, Fox A, Gonsalves NP, Gupta SK, Katzka DA, Kinoshita Y, Menard-Katcher C, Kodroff E, Metz DC, Miehlke S, Muir AB, Mukkada VA, Murch S, Nurko S, Ohtsuka Y, Orel R, Papadopoulou A, Peterson KA, Philpott H, Putnam PE, Richter JE, Rosen R, Rothenberg ME, Schoepfer A, Scott MM, Shah N, Sheikh J, Souza RF, Strobel MJ, Talley NJ, Vaezi MF, Vandenplas Y, Vieira MC, Walker MM, Wechsler JB, Wershil BK, Wen T, Yang GY, Hirano I, Bredenoord AJ. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018 Oct;155(4):1022-1033.e10. doi: 10.1053/j.gastro.2018.07.009. Epub 2018 Sep 6.