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: Active, not recruiting
• 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

Expanded Access

Available outside the clinical trial. See expanded access record.

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
    • Saint 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: 4 months to 9 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	Time Frame
Proportion of patients achieving peak esophageal intraepithelial eosinophil count ≤6 eos/hpf (400×)	At Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf	Part A	At Week 16
Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf	Part B	At Week 52
Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf	Part C	At Week 100
Proportion of patients achieving peak esophageal intraepithelial eosinophil count of <15 eos/hpf	Part C	At Week 160
Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf)	Part A	Baseline to Week 16
Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf)	Part B	Baseline to Week 52
Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf)	Part C	Baseline to Week 100
Percent change in peak esophageal intraepithelial eosinophil count (eos/hpf)	Part C	Baseline to Week 160
Absolute change in mean eosinophilic esophagitis (EoE) Histology Scoring System (EoE-HSS)	Part A The EoEHSS assesses the severity (grade) and extent (stage) of abnormalities using a 4-point scale (0 normal; 3 maximum change).	Baseline to Week 16
Absolute change in mean EoE-HSS	Part B The EoEHSS as stated above.	Baseline to Week 52
Absolute change in mean EoE-HSS	Part C The EoEHSS as stated above.	Baseline to Week 100
Absolute change in mean EoE-HSS	Part C The EoEHSS as stated above.	Baseline to Week 160
Absolute change in Eosinophilic Esophagitis-Endoscopic Reference (EoE EREFS)	Part A EoE esophageal characteristics will be analyzed based on the EoE-EREFS, a scoring system for inflammatory and remodeling features of disease using both overall scores and scores for each individual characteristic. The proximal and distal esophageal regions will be scored separately; The score for each region ranges from 0 to 9 and the overall score ranges from 0 to 18.	Baseline to Week 16
Absolute change in EoE-EREFS	Part B EoE esophageal characteristics will be analyzed based on the EoE-EREFS, as stated above.	Baseline to Week 52
Absolute change in EoE-EREFS	Part C EoE esophageal characteristics will be analyzed based on the EoE-EREFS, as stated above.	Baseline to Week 100
Absolute change in EoE-EREFS	Part C EoE esophageal characteristics will be analyzed based on the EoE-EREFS, as stated above.	Baseline to Week 160
Change in the type 2 inflammation transcriptional signature	Part A	Baseline at Week 16
Change in the type 2 inflammation transcriptional signature	Part B	Baseline at Week 52
Change in the proportion of days with 1 or more EoE signs as measured by the Pediatric EoE Sign/Symptom Questionnaire- Caregiver version (PESQ-C)	Part A: For patients aged ≥1 to <12 years The PESQ-C is an observer-reported outcome measure intended to be completed independently by caregivers. The PESQ-C will measure occurrence of signs of EoE and will be completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding the week 16 visit will be used to calculate the proportion of days or total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE signs.	Baseline to Week 16
Change in the proportion of days with 1 or more EoE signs as measured by the PESQ-C	Part B: For patients aged ≥1 to <12 years The PESQ-C as stated above.	Baseline to Week 52
Number of sign-free days during the 14-day period preceding week 16 as measured by the PESQ-C	Part A: For patients aged ≥1 to <12 years The PESQ-C as stated above.	Up to Week 16
Number of sign-free days during the 14-day period preceding week 52 as measured by the PESQ-C	Part B: For patients aged ≥1 to <12 years The PESQ-C as stated above.	Up to Week 52
Change in the proportion of total segments within a day with 1 or more EoE signs as measured by the PESQ-C	Part A: For patients aged ≥1 to <12 years The PESQ-C as stated above.	Baseline to Week 16
Change in the proportion of total segments within a day with 1 or more EoE signs as measured by the PESQ-C	Part B: For patients aged ≥1 to <12 years The PESQ-C as stated above.	Baseline to Week 52
Change in the proportion of days with 1 or more EoE symptoms as measured by the Pediatric EoE Sign/Symptom Questionnaire- Patient version (PESQ-P)	Part A: For patients aged ≥8 to <12 years The PESQ-P is a patient-reported outcome measure intended to be completed independently by EoE patients. The PESQ-P will measure occurrence and severity of EoE symptoms and will be completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding the week 16 visit will be used to calculate the proportion of days or total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms.	Baseline to Week 16
Change in the proportion of days with 1 or more EoE symptoms as measured by the PESQ-P	Part B: For patients aged ≥8 to <12 years The PESQ-P as stated above.	Baseline to Week 52
Number of symptom-free days during the 14-day period preceding week 16 as measured by the PESQ-P	Part A: For patients aged ≥8 to <12 years The PESQ-P as stated above.	Up to Week 16
Number of symptom-free days during the 14-day period preceding week 52 as measured by the PESQ-P	Part B: For patients aged ≥8 to <12 years The PESQ-P as stated above.	Up to Week 52
Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by the PESQ-P	Part A: For patients aged ≥8 to <12 years The PESQ-P as stated above.	Baseline to Week 16
Change in the proportion of total segments within a day with 1 or more EoE symptoms as measured by the PESQ-P	Part B: For patients aged ≥8 to <12 years The PESQ-P as stated above.	Baseline to Week 52
Change in total score as measured by the PEESSv2.0-caregiver version questionnaire	Part A: For patients aged ≥1 to <12 years The PEESSv2.0-caregiver version assesses the frequency and severity of EoE symptoms among pediatric patients (Franciosi, 2011). The PEESSv2.0 consists of 20 items and has a one-month recall period. The total score ranges from 0 to 100; higher scores indicate greater symptom burden of among pediatric EoE patients	Baseline to Week 16
Change in total score as measured by the PEESSv2.0- caregiver version questionnaire	Part C The PEESSv2.0-caregiver version as stated above.	Baseline to Week 160
Normalized Enrichment Scores (NES) for the relative change in the EoE diagnostic panel (EDP) transcriptome signature	Part A NES reflects the degree to which the activity level of a set of transcripts is overrepresented at the extremes (top or bottom) of the entire ranked list of transcripts within a sample and is normalized by accounting for the number of transcripts in the set (Barbie, 2009)(Subramanian, 2005). NES scores will be calculated for each transcriptome signature for each sample for statistical analyses.	Baseline to Week 16
NES for the relative change in the EDP transcriptome signature	Part B NES as stated above.	Baseline to Week 52
NES for the relative change in the EDP transcriptome signature	Part C NES as stated above.	Baseline to Week 100
NES for the relative change in the EDP transcriptome signature	Part C NES as stated above.	Baseline to Week 160
NES for the relative change in the type 2 inflammation transcriptome signature	Part A NES as stated above.	Baseline to Week 16
NES for the relative change in the type 2 inflammation transcriptome signature	Part B NES as stated above.	Baseline to Week 52
NES for the relative change in the type 2 inflammation transcriptome signature	Part C NES as stated above.	Baseline to Week 100
Change in body weight for age percentile	Part B	Baseline at Week 52
Change in body weight for age percentile	Part C	Baseline up to Week 160
Change in body mass index for age z-score	Part B: For patients ≥2 years of age	Baseline to Week 52
Change in body mass index for age z-score	Part C: For patients ≥2 years of age	Baseline to up to Week 160
Change in weight for age z-score	Part B	Baseline to Week 52
Change in weight for age z-score	Part C	Baseline up to Week 160
Change in weight for height z-score	Part B	Baseline to Week 52
Change in weight for height z-score	Part C	Baseline up to Week 160
Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf (400×)	Part C	At Week 100
Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf (400×)	Part C	At Week 160
Proportion of patients (with food elimination diet regimens at baseline) that have a re-introduction of a previously eliminated food group	Part C	Baseline by Week 100
Proportion of patients (with food elimination diet regimens at baseline) that have a re-introduction of a previously eliminated food group	Part C	Baseline by Week 160
Incidence of treatment-emergent adverse events (TEAEs)	Part A	Up to Week 16
Incidence of TEAEs	Part B	Up to Week 52
Incidence of TEAEs	Part C	Up to Week 160
Incidence of treatment-emergent serious adverse events (SAEs)	Part A	Up to Week 16
Incidence of treatment-emergent SAEs	Part B	Up to Week 52
Incidence of treatment-emergent SAEs	Part C	Up to Week 160
Incidence of treatment-emergent adverse events of special interest (AESIs)	Part A	Up to Week 16
Incidence of treatment-emergent AESIs	Part B	Up to Week 52
Incidence of treatment-emergent AESIs	Part C	Up to Week 160
Incidence of TEAEs leading to permanent discontinuation of study treatment	Part A	Up to Week 16
Incidence of TEAEs leading to permanent discontinuation of study treatment	Part B	Up to Week 52
Incidence of TEAEs leading to permanent discontinuation of study treatment	Part C	Up to Week 160
Incidence of treatment-emergent Anti-drug antibody (ADA) responses and titer	Part A	Up to Week 16
Incidence of treatment-emergent ADA responses and titer	Part B	Up to Week 52
Incidence of treatment-emergent ADA responses and titer	Part C	Up to Week 160
Concentration of functional dupilumab in serum		Baseline to end of study, Up to Week 160

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): June 2, 2022
• Study Completion (Estimated): July 7, 2025

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 (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Gastrointestinal Diseases; Gastroenteritis; Hypersensitivity; Esophageal Diseases; Leukocyte Disorders; Eosinophilia; Eosinophilic Esophagitis; Esophagitis
• 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