Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis (EoE) (EoE KIDS)

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Dupilumab in Pediatric Patients With Active Eosinophilic Esophagitis

The Primary objective is to demonstrate the efficacy of dupilumab treatment compared with placebo in pediatric patients with active eosinophilic esophagitis (EoE) based on histologic improvement meeting validated histologic criteria.

The Secondary objectives are:

• To demonstrate the efficacy of dupilumab compared to placebo in pediatric patients with active EoE after 16 weeks of treatment as assessed by endoscopic visual measurements of disease activity using the Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) and histologic abnormalities as measured by the EoE Histology Scoring System (EoE-HSS)
• To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 16 weeks in pediatric patients with active EoE
• To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation
• To study the effects of dupilumab on the type 2 inflammation gene expression signature
• To evaluate the concentration-time profile of functional dupilumab in serum in this population
• To assess efficacy of long-term (up to 160 weeks) dupilumab treatment
• To assess the impact of dupilumab treatment on changes in weight and growth during the extended active period and open-label extension period of the study
• To assess safety, tolerability, and immunogenicity of long-term (up to 160 weeks) dupilumab treatment
• To evaluate the impact of dupilumab treatment on EoE signs and symptoms

Study Overview

• Status: Completed
• Conditions: Eosinophilic Esophagitis (EoE)
• Intervention / Treatment: Drug: Dupilumab; Drug: Matching Placebo

Detailed Description

This is a 3-part study:

• Part A: Double-blind 16-week treatment period
• Part B: 36-week extended active treatment period
• Part C: Up to108 weeks open-label extension period

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Regeneron Study Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Regeneron Study Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Regeneron Study Site
  • California
    • Los Angeles, California, United States, 90027
      • Regeneron Study Site
    • San Francisco, California, United States, 94143
      • Regeneron Study Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Regeneron Study Site
  • Florida
    • St. Petersburg, Florida, United States, 33701
      • Regeneron Study Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Regeneron Study Site
    • Atlanta, Georgia, United States, 30342
      • Regeneron Study Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Regeneron Study Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Regeneron Study Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Regeneron Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Regeneron Study Site
    • Boston, Massachusetts, United States, 02111
      • Regeneron Study Site
    • Boston, Massachusetts, United States, 02115
      • Regeneron Study Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Regeneron Study Site
  • New York
    • New York, New York, United States, 10029
      • Regeneron Study Site
    • New York, New York, United States, 10032
      • Regeneron Study Site
    • New York, New York, United States, 10065
      • Regeneron Study Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Regeneron Study Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Regeneron Study Site
    • Cleveland, Ohio, United States, 44106
      • Regeneron Study Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Regeneron Study Site
  • Texas
    • Dallas, Texas, United States, 75207
      • Regeneron Study Site
    • Fort Worth, Texas, United States, 76104
      • Regeneron Study Site
    • Houston, Texas, United States, 77030
      • Regeneron Study Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Regeneron Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 7 years (Child)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. A documented diagnosis of eosinophilic esophagitis (EoE)
2. Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration

Key Exclusion Criteria:

1. Body weight <5 kg or ≥60 kg at screening
2. Other causes of esophageal eosinophilia
3. Active Helicobacter pylori
4. History of Crohn's disease, ulcerative colitis, celiac disease, or prior esophageal surgery
5. Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening
6. Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline standard of care endoscopy
7. History of bleeding disorders or esophageal varices that, in the opinion of the investigator, would put the patient at undue risk for significant complications from an endoscopy procedure
8. Active parasitic infection or suspected parasitic infection
9. Known or suspected immunodeficiency disorder

Key Exclusion for Patients Re-Entering the Study (for Entry into Part C, as defined in protocol):

1. Patients who are ≥12 years old, weigh ≥40 kg (or minimum weight for which dupilumab is approved for EoE), and dupilumab is commercially available for the treatment of EoE in their country
2. Patients who, during their previous participation in this clinical trial, developed an SAE and/or AE deemed related to dupilumab, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient
3. Patients who did not undergo endoscopy with biopsies at week 16 and/or week 52 or prior to receiving rescue treatment Note: If the endoscopy with biopsies could not occur due to COVID-19 restrictions and rescue treatment was needed to be initiated without delay, these patients will be eligible to participate in Part C
4. Patients who became pregnant during their previous participation in this dupilumab clinical trial
5. Patients who, during their previous participation in this trial, were prematurely withdrawn because of a protocol violation, poor compliance, or inability to complete required study assessments

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A - High Dose; Part A consists of a 16-week double-blind treatment period. Patients will be randomized to receive dupilumab or placebo subcutaneous (SC) administration at tiered dosing regimens based on body weight	Drug: Dupilumab; Single-use, prefilled syringe; Other Names: •DUPIXENT; •REGN668; •SAR231893; Drug: Matching Placebo; Matching formulation and regimen (depending on the weight tier) as dupilumab without the active substance
Experimental: Part A - Low Dose; Part A consists of a 16-week double-blind treatment period. Patients will be randomized to receive dupilumab or placebo subcutaneous (SC) administration at tiered dosing regimens based on body weight	Drug: Dupilumab; Single-use, prefilled syringe; Other Names: •DUPIXENT; •REGN668; •SAR231893; Drug: Matching Placebo; Matching formulation and regimen (depending on the weight tier) as dupilumab without the active substance
Experimental: Part B - High Dose; Part B consists of a 36-week extended active treatment period. All patients to receive subcutaneous (SC) administration at tiered dosing regimens based on body weight	Drug: Dupilumab; Single-use, prefilled syringe; Other Names: •DUPIXENT; •REGN668; •SAR231893; Drug: Matching Placebo; Matching formulation and regimen (depending on the weight tier) as dupilumab without the active substance
Experimental: Part B - Low Dose; Part B consists of a 36-week extended active treatment period. All patients to receive subcutaneous (SC) administration at tiered dosing regimens based on body weight	Drug: Dupilumab; Single-use, prefilled syringe; Other Names: •DUPIXENT; •REGN668; •SAR231893; Drug: Matching Placebo; Matching formulation and regimen (depending on the weight tier) as dupilumab without the active substance
Experimental: Part C - High Dose; Part C consists of up to 108-week open-label extension period. All patients will receive higher exposure dupilumab subcutaneous (SC) administration at tiered dosing regimens based on body weight. No matching placebo administered in Part C.	Drug: Dupilumab; Single-use, prefilled syringe; Other Names: •DUPIXENT; •REGN668; •SAR231893

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of Less Than or Equal to (≤) 6 Eosinophils/High Power Field (Eos/Hpf) at Week 16	Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.	At Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16	Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.	At Week 16
Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16	Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available. Least squared (LS) mean and standard error (SE) from analysis of covariance (ANCOVA) model with Baseline measurement as covariate and the treatment, baseline weight group strata as fixed factors.	Baseline, Week 16
Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16	EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean grade scores summed over the 3 regions was the final score used in primary analysis, the mean grade score ranged from 0 to 3, with higher score indicating more severe.	Baseline, Week 16
Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16	EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean stage scores summed over the 3 regions was the final score used in primary analysis, the mean stage score ranged from 0 to 3, with higher score indicating more severe.	Baseline, Week 16
Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16	A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for T2INF reflect the expression at Week 16 relative to Baseline of the pre-specified gene set as a way to evaluate normalization of type 2 inflammation with treatment. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have a minimum/maximum score.	Baseline, Week 16
Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16	A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at Week 16 relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.	Baseline, Week 16
Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16	The EoE-EREFS is a validated endoscopic scoring system for inflammatory and remodeling features of EoE including edema, rings, exudates, furrows, and stricture. The score was assessed in the proximal and distal esophageal regions with each region scored from 0 to 9 with total scores ranging from 0 to 18. Higher scores indicate worse endoscopic inflammatory and remodeling findings.	Baseline, Week 16
Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs as Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 16 (for Participants Aged ≥1 to <12 Years)	PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. PESQ-C measures the signs of EoE observed by the caregiver, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms.	Baseline, Week 16
Part A: Number of Sign-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years)	PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measures the signs of EoE observed by the caregiver, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the multiple imputations approach was used for the missing data due to other reasons. LS mean SE derived from ANCOVA model.	Week 16
Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 16	PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms.	Baseline, Week 16
Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 16	The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to <12 years of age. The PESQ-P measured occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms.	Baseline, Week 16
Part A: Number of Symptom-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years)	The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to <12 years of age. The PESQ-P measures the signs of EoE, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. The PESQ-P score was calculated based on the daily responses over a 14-day period (i.e., the 14 days prior to the baseline visit and the week 16 visit). The score ranges from 0 to 1. WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the multiple imputations approach was used for the missing data due to other reasons. LS Mean SE from ANCOVA.	Week 16
Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 16	The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to <12 years of age. The PESQ-P measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms.	Baseline, Week 16
Part A: Change From Baseline in Total Score as Measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) Version 2.0 Caregiver Version (PEESSv2.0-C) at Week 16	The PEESSv2.0-C is a caregiver-reported outcome measure that assesses the frequency and severity of EoE symptoms among pediatric participants. The PEESSv2.0-C consists of 20 items and has a one-month recall period. Each item had a 0-4 scale, which was transformed to 0-100 as follows: 0 = 0, 1 = 25, 2 = 50, 3 = 75, 4 = 100. The mean total PEESSv2.0 score was computed as the sum of all the item scores over the number of items answered. The total PEESSv2.0-C score ranges from 0 to 100 where higher scores indicate greater symptom burden among pediatric EoE participants. Values after first rescue treatment use were set to missing (censoring). WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the MI approach was used for the missing data due to other reasons. LS mean SE from ANCOVA model.	Baseline, Week 16
Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16	Concentration of functional dupilumab in serum at Baseline, Week 4 and 16 was reported in this outcome measure.	Baseline, Week 4 and 16
Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52	Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.	At Week 52
Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52	Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.	At Week 52
Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52	Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.	Baseline, Week 52
Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52	EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean grade scores summed over the 3 regions was the final score used in primary analysis, the mean grade score ranged from 0 to 3, with higher score indicating more severe.	Baseline, Week 52
Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52	EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean stage scores summed over the 3 regions was the final score used in primary analysis, the mean stage score ranged from 0 to 3, with higher score indicating more severe.	Baseline, Week 52
Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52	The EoE-EREFS is a validated endoscopic scoring system for inflammatory and remodeling features of EoE including edema, rings, exudates, furrows, and stricture. The score was assessed in the proximal and distal esophageal regions with each region scored from 0 to 9 with total scores possibly ranging from 0 to 18. Higher scores indicate worse endoscopic inflammatory and remodeling findings.	Baseline, Week 52
Part B: Number of Sign-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years)	PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study.	Week 52
Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 52	The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to <12 years of age. The PESQ-P measured occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms.	Baseline, Week 52
Part B: Number of Symptom-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years)	The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to <12 years of age. The PESQ-P measures the signs of EoE, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food.	Week 52
Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 52	The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to <12 years of age. The PESQ-P measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms.	Baseline, Week 52
Part B: Change From Baseline in Body Weight for Age Percentile at Week 52	Body weight for age percentile was calculated based on the growth charts from the Centers for Disease Control and Prevention (CDC) for ages 0 to 20 years (for ages 2 to <12 years) and World Health Organization (WHO) growth charts for ages 0 to <2 years (for ages 1 to <2 years). These charts included a set of smoothed percentiles along with CDC LMS (Lambda-Mu-Sigma) parameters to allow the calculation of percentiles.	Baseline, Week 52
Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52	Concentration of functional dupilumab in serum at Week 32 and 52 was reported in this outcome measure.	Week 32 and 52
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug	An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose resulted in death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or a medically important event. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. An AESI was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate.	From Baseline up to Week 16 in Part A
Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug	An AE was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose resulted in death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or a medically important event. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. An AESI was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate.	From Week 16 up to Week 52 in Part B
Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response	Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level <1000, moderate as 1000 to 10000 and high as >10000.	From Baseline up to Week 16 in Part A
Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category	Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level <1000, moderate as 1000 to 10000 and high as >10000.	From Baseline up to Week 16 in Part A
Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 52	PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study.	Baseline, Week 52
Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 52	PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measured the occurrence of signs of EoE and was completed once daily via an electronic diary.	Baseline, Week 52
Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52	A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.	Baseline, Week 52
Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52	A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for T2INF reflect the expression at post-baseline relative to Baseline of the pre-specified gene set as a way to evaluate normalization of type 2 inflammation with treatment. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.	Baseline, Week 52
Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52	BMI for age z-score indicates how much higher or lower a participant's BMI for age is relative to a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention [CDC] for ages 0 to 20 years [for ages 2 to <12 years]). A z-score of "0" represents the population mean. An increase in the mean change in BMI for age z-score (ie, increase in the standard deviation [SD] from the reference growth chart) indicates an increase in BMI for age relative to the reference.	Baseline, Week 52
Part B: Change From Baseline in Weight for Age Z-score at Week 52	Weight for age z-score indicates how much higher or lower a participant's weight for age is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years [for ages 2 to <12 years] and World Health Organization (WHO) growth charts for ages 0 to <2 years [for ages 1 to <2 years]). A z-score of "0" represents the population mean. An increase in the mean change in weight for age z-score (increase in the SD from the reference growth chart) indicates an increase in weight for age relative to the reference.	Baseline, Week 52
Part B: Change From Baseline in Body Weight From Height Z-score at Week 52	Weight for height z-score indicates how much higher or lower a participant's weight for height is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years [for ages 2 to <12 years] and WHO growth charts for ages 0 to <2 years [for ages 1 to <2 years]). A z-score of "0" represents the population mean. An increase in the mean change in weight for height z-score (increase in the SD from the reference growth chart) indicates an increase in weight for height relative to the reference.	Baseline, Week 52
Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer	Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level <1000, moderate as 1000 to 10000 and high as >10000. No participant exhibited a treatment-emergent ADA response in Part B and titer was not reported.	From Week 16 up to Week 52 in Part B
Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 100		At Week 100
Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 160		At Week 160
Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 100		Baseline to Week 100
Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 160		Baseline to Week 160
Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 100		Baseline to Week 100
Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 160		Baseline to Week 160
Part C: Absolute Change in EoE-EREFS From Baseline to Week 100		Baseline to Week 100
Part C: Absolute Change in EoE-EREFS From Baseline to Week 160		Baseline to Week 160
Part C: Change in Total Score as Measured by the PEESSv2.0- Caregiver Version Questionnaire From Baseline to Week 100	The PEESSv2.0-C is a caregiver-reported outcome measure that assesses the frequency and severity of EoE symptoms among pediatric participants. The PEESSv2.0-C consists of 20 items and has a one-month recall period. Each item had a 0-4 scale, which was transformed to 0-100 as follows: 0 = 0, 1 = 25, 2 = 50, 3 = 75, 4 = 100. The mean total PEESSv2.0 score was computed as the sum of all the item scores over the number of items answered. The total PEESSv2.0-C score ranges from 0 to 100 where higher scores indicate greater symptom burden among pediatric EoE participants.	Baseline to Week 100
Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 100	A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.	Baseline to Week 100
Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 160	A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.	Baseline to Week 160
Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature Baseline to Week 100		Baseline to Week 100
Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature From Baseline to Week 160		Baseline to Week 160
Part C: Change in Body Weight for Age Percentile From Baseline up to Week 100	Body weight for age percentile was calculated based on the growth charts from the Centers for Disease Control and Prevention (CDC) for ages 0 to 20 years (for ages 2 to <12 years) and World Health Organization (WHO) growth charts for ages 0 to <2 years (for ages 1 to <2 years). These charts included a set of smoothed percentiles along with CDC LMS (Lambda-Mu-Sigma) parameters to allow the calculation of percentiles.	Baseline up to Week 100
Part C: Change in Body Mass Index for Age Z-score From Baseline up to Week 100	Difference in the 100-week change from baseline in BMI-for-age Z-score. BMI-for-age Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention [CDC] for ages 0 to 20 years [for ages 2 to <12 years]. A z-score of "0" represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean.	Baseline up to Week 100
Part C: Change in Weight for Age Z-score From Baseline up to Week 100	Difference in the 100-week change from baseline in weight-for-age Z-score. Weight-for-age Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention [CDC] for ages 0 to 20 years [for ages 2 to <12 years]. A z-score of "0" represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean.	Baseline up to Week 100
Part C: Change in Weight for Age Z-score From Baseline up to Week 160	Weight for age z-score indicates how much higher or lower a participant's weight for age is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years [for ages 2 to <12 years] and World Health Organization (WHO) growth charts for ages 0 to <2 years [for ages 1 to <2 years]). An increase in the mean change in weight for age z-score (increase in the SD from the reference growth chart) indicates an increase in weight for age relative to the reference.	Baseline up to Week 160
Part C: Change in Weight for Height Z-score From Baseline up to Week 100	Difference in the 100-week change from baseline in Weight for height Z-score. Weight for height Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention [CDC] for ages 0 to 20 years [for ages 2 to <12 years]. A z-score of "0" represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean.	Baseline up to Week 100
Part C: Change in Weight for Height Z-score From Baseline up to Week 160	Weight for height z-score indicates how much higher or lower a participant's weight for height is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years [for ages 2 to <12 years] and WHO growth charts for ages 0 to <2 years [for ages 1 to <2 years]). An increase in the mean change in weight for height z-score (increase in the SD from the reference growth chart) indicates an increase in weight for height relative to the reference.	Baseline up to Week 160
Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 100		At Week 100
Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 160		At Week 160
Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 100		Baseline up to Week 100
Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 160		Baseline up to Week 160
Part C: Number of Participants With TEAEs		Up to Week 152
Part C: Number of Participants With Treatment-emergent SAEs		Up to Week 152
Part C: Number of Participants With Treatment-emergent AESIs		Up to Week 152
Part C: Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Treatment		Up to Week 152
Part C: Number of Participants With Treatment-emergent ADA Responses		From Week 52 up to Week 152
Part C: Concentration of Functional Dupilumab in Serum at Week 100		At Week 100

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Chehade M, Dellon ES, Spergel JM, Collins MH, Rothenberg ME, Pesek RD, Hirano I, Liu R, Laws E, Mortensen E, Martincova R, Shabbir A, McCann E, Kamal MA, Kosloski MP, Hamilton JD, Samuely C, Lim WK, Wipperman MF, Farrell A, Patel N, Yancopoulos GD, Glotfelty L, Maloney J. Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age. N Engl J Med. 2024 Jun 27;390(24):2239-2251. doi: 10.1056/NEJMoa2312282.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): June 2, 2022
• Study Completion (Actual): May 14, 2024

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 17, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Estimated): October 27, 2025
• Last Update Submitted That Met QC Criteria: October 13, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Digestive System Diseases; Gastrointestinal Diseases; Hypersensitivity, Immediate; Hypersensitivity; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Esophageal Diseases; Gastroenteritis; Esophagitis; Hemic and Lymphatic Diseases; Eosinophilic Esophagitis; dupilumab
• Other Study ID Numbers: R668-EE-1877; 2019-003078-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No