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

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Eosinophilic Esophagitis (EoE)

Treatments: Drug: Matching Placebo; Drug: Dupilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04394351

2019-003078-24 (EudraCT Number)

R668-EE-1877

Details and patient eligibility

About

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

Full 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

Enrollment: 102 patients

Sex: All

Ages: 1 to 11 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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102 participants in 5 patient groups

Part A - High Dose

Experimental group

Description:

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

Treatment:

Drug: Dupilumab

Drug: Matching Placebo

Part A - Low Dose

Experimental group

Description:

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

Treatment:

Drug: Dupilumab

Drug: Matching Placebo

Part B - High Dose

Experimental group

Description:

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

Treatment:

Drug: Dupilumab

Drug: Matching Placebo

Part B - Low Dose

Experimental group

Description:

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

Treatment:

Drug: Dupilumab

Drug: Matching Placebo

Part C - High Dose

Experimental group

Description:

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.

Treatment:

Drug: Dupilumab