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

Phase 3

Completed

Conditions: Eosinophilic Esophagitis (EoE)

Interventions: Drug: Dupilumab
Drug: Matching Placebo

Registration Number: NCT04394351

Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary: 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

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 102

Inclusion Criteria

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

Key

Exclusion Criteria

Body weight <5 kg or ≥60 kg at screening
Other causes of esophageal eosinophilia
Active Helicobacter pylori
History of Crohn's disease, ulcerative colitis, celiac disease, or prior esophageal surgery
Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening
Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline standard of care endoscopy
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
Active parasitic infection or suspected parasitic infection
Known or suspected immunodeficiency disorder

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

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
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
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
Patients who became pregnant during their previous participation in this dupilumab clinical trial
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A - High Dose	Dupilumab	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
Part A - High Dose	Matching Placebo	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
Part A - Low Dose	Dupilumab	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
Part A - Low Dose	Matching Placebo	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
Part B - High Dose	Dupilumab	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
Part B - High Dose	Matching Placebo	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
Part B - Low Dose	Dupilumab	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
Part B - Low Dose	Matching Placebo	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
Part C - High Dose	Dupilumab	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.

Primary Outcome Measures

Name	Time	Method
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	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.

Secondary Outcome Measures

Name	Time	Method
Part C: Absolute Change in Mean EoE-HSS	Baseline to Week 160
Part C: Incidence of Treatment-emergent AESIs	Up to Week 160
Part C: Concentration of Functional Dupilumab in Serum	Baseline to end of study, Up to Week 160
Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16	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.
Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16	Baseline, 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.
Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16	Baseline, 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.
Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16	Baseline, 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.
Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16	Baseline, 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.
Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16	Baseline, 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.
Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16	Baseline, 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.
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)	Baseline, 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. 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.
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	Baseline, 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.
Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16	Baseline, Week 4 and 16	Concentration of functional dupilumab in serum at Baseline, Week 4 and 16 was reported in this outcome measure.
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)	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 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.
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	Baseline, 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.
Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52	Baseline, 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.
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	Baseline, 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. 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.
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	Baseline, 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.
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	Baseline, 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.
Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52	Baseline, 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.
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	From Baseline up to Week 16 in Part A	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.
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	From Week 16 up to Week 52 in Part B	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.
Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response	From Baseline up to Week 16 in Part A	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.
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)	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 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.
Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52	Baseline, 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.
Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52	Baseline, 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.
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)	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.
Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52	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.
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	Baseline, 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.
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)	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 measures the signs of EoE, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food.
Part C: NES for the Relative Change in the EDP Transcriptome Signature	Baseline to Week 160
Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature	Baseline to Week 100
Part C: Change in Body Mass Index for Age Z-score	Baseline to up to Week 160
Part C: Change in Weight for Age Z-score	Baseline up to Week 160
Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52	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.
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	Baseline, 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. 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.
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	Baseline, 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.
Part C: Incidence of TEAEs Leading to Permanent Discontinuation of Study Treatment	Up to Week 160
Part C: Incidence of Treatment-emergent ADA Responses and Titer	Up to Week 160
Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52	Baseline, 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 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.
Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52	Baseline, 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 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 minimum/maximum score.
Part B: Change From Baseline in Body Weight for Age Percentile at Week 52	Baseline, 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.
Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52	Baseline, 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 \[for ages 2 to \<12 years\]). 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.
Part B: Change From Baseline in Weight for Age Z-score at Week 52	Baseline, 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 \[for ages 1 to \<2 years\]). 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.
Part B: Change From Baseline in Body Weight From Height Z-score at Week 52	Baseline, 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 \[for ages 1 to \<2 years\]). 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.
Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52	Week 32 and 52	Concentration of functional dupilumab in serum at Week 32 and 52 was reported in this outcome measure.
Part C: Change in Weight for Height Z-score	Baseline up to Week 160
Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category	From Baseline up to Week 16 in Part A	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.
Part C: Proportion of Patients Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf	At Week 160
Part C: Absolute Change in EoE-EREFS	Baseline to Week 160
Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer	From Week 16 up to Week 52 in Part B	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 patient exhibited a treatment-emergent ADA response in Part B and titer was not reported.
Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf)	Baseline to Week 160
Part C: Change in Total Score as Measured by the PEESSv2.0- Caregiver Version Questionnaire	Baseline to Week 160
Part C: Change in Body Weight for Age Percentile	Baseline up to Week 160
Part C: Proportion of Patients Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×)	At Week 160
Part C: Proportion of Patients (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group	Baseline by Week 160
Part C: Incidence of TEAEs	Up to Week 160
Part C: Incidence of Treatment-emergent SAEs	Up to Week 160