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

NCT04394351 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: R668-EE-18772019-003078-24
• Study Type: interventional
• Target: 102
• Locations: 2 countries
• Sites: 27

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

Conditions

Eosinophilic Esophagitis (EoE)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (68)

• Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16

  At Week 16

• Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16

  Baseline, Week 16

• Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16

  Baseline, Week 16

• Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16

  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

  Baseline, Week 16

Study Arms (5)

Part A - High Dose

EXPERIMENTAL

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; Drug: Matching Placebo

Part A - Low Dose

EXPERIMENTAL

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; Drug: Matching Placebo

Part B - High Dose

EXPERIMENTAL

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; Drug: Matching Placebo

Part B - Low Dose

EXPERIMENTAL

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; Drug: Matching Placebo

Part C - High Dose

EXPERIMENTAL

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

Interventions

Dupilumab DRUG

Single-use, prefilled syringe

Also known as: •DUPIXENT, •REGN668, •SAR231893

Part A - High Dose; Part A - Low Dose; Part B - High Dose; Part B - Low Dose; Part C - High Dose

Matching Placebo DRUG

Matching formulation and regimen (depending on the weight tier) as dupilumab without the active substance

Part A - High Dose; Part A - Low Dose; Part B - High Dose; Part B - Low Dose

Eligibility Criteria

• Age: 1 Year - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (27)

Regeneron Study Site

Phoenix, Arizona, 85016, United States

Location

Regeneron Study Site

Little Rock, Arkansas, 72202, United States

Location

Regeneron Study Site

Los Angeles, California, 90027, United States

Location

Regeneron Study Site

San Francisco, California, 94143, United States

Location

Regeneron Study Site

Aurora, Colorado, 80045, United States

Location

Regeneron Study Site

St. Petersburg, Florida, 33701, United States

Location

Regeneron Study Site

Atlanta, Georgia, 30322, United States

Location

Regeneron Study Site

Atlanta, Georgia, 30342, United States

Location

Regeneron Study Site

Chicago, Illinois, 60611, United States

Location

Regeneron Study Site

Indianapolis, Indiana, 46202, United States

Location

Regeneron Study Site

Iowa City, Iowa, 52242, United States

Location

Regeneron Study Site

Boston, Massachusetts, 02111, United States

Location

Regeneron Study Site

Boston, Massachusetts, 02114, United States

Location

Regeneron Study Site

Boston, Massachusetts, 02115, United States

Location

Regeneron Study Site

Lincoln, Nebraska, 68510, United States

Location

Regeneron Study Site

New York, New York, 10029, United States

Location

Regeneron Study Site

New York, New York, 10032, United States

Location

Regeneron Study Site

New York, New York, 10065, United States

Location

Regeneron Study Site

Chapel Hill, North Carolina, 27599, United States

Location

Regeneron Study Site

Cincinnati, Ohio, 45229, United States

Location

Regeneron Study Site

Cleveland, Ohio, 44106, United States

Location

Regeneron Study Site

Philadelphia, Pennsylvania, 19104, United States

Location

Regeneron Study Site

Dallas, Texas, 75207, United States

Location

Regeneron Study Site

Fort Worth, Texas, 76104, United States

Location

Regeneron Study Site

Houston, Texas, 77030, United States

Location

Regeneron Study Site

Milwaukee, Wisconsin, 53226, United States

Location

Regeneron Study Site

London, Ontario, N6A 5W9, Canada

Location

Related Publications (1)

• 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.

  PMID: 38924731 DERIVED

MeSH Terms

Conditions

Eosinophilic Esophagitis

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc.

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 19, 2020
• Study Start: September 1, 2020
• Primary Completion: June 2, 2022
• Study Completion: May 14, 2024
• Last Updated: October 27, 2025
• Results First Posted: August 27, 2024

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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).

Locations

US (26); CA (1)