Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)

Regeneron Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Eosinophilic Esophagitis

Treatments: Drug: Dupilumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03633617

2018-000844-25 (EudraCT Number)

R668-EE-1774

Details and patient eligibility

About

The primary objectives of the study by study part are:

Part A:

To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures and to inform/confirm the final sample size determination for Part B.

Part B:

To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with EoE after 24 weeks of treatment as assessed by histological and clinical measures.

Part C:

To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with EoE after up to 52 weeks of treatment as assessed by histological and clinical measures.

The secondary objectives of the study are:

• To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with EoE
• To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with EoE, using descriptive analyses
• To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation
• To demonstrate the efficacy of dupilumab treatment compared to placebo after 24 weeks and 52 weeks of treatment in adult and adolescent patients with EoE who have previously received swallowed topical corticosteroids

Enrollment: 321 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria (Parts A & B):

• A documented diagnosis of EoE by endoscopic biopsy
• Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration
• History (by patient report) of an average of at least 2 episodes of dysphagia (with intake of solids) per week in the 4 weeks prior to screening

Key Exclusion Criteria (Parts A & B):

• Body weight ≤40 kg
• Prior participation in a dupilumab clinical trial, or past or current treatment with dupilumab
• Initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food group in the 6 weeks prior to screening.
• Other causes of esophageal eosinophilia or the following conditions: hypereosinophilic syndrome and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
• Active Helicobacter pylori infection
• History of achalasia, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery
• Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening
• History of bleeding disorders or esophageal varices
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study

Key Exclusion Criteria (Part C):

• Participants who, during Part A or Part B, developed a serious adverse event (SAE) and/or adverse event (AE) deemed related to study drug, which in the opinion of the investigator could indicate that continued treatment with study drug may present an unreasonable risk for the participant
• Participants who became pregnant during Part A or Part B
• Participants who are prematurely discontinued from study drug due to an AE (patients who are prematurely discontinued from study drug due to lack of efficacy are eligible to enter Part C)
• Patients who did not undergo endoscopy with biopsies prior to receiving rescue treatment

Note: Other inclusion/ exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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321 participants in 3 patient groups

Part A: Dupilumab or Placebo

Experimental group

Description:

Part A consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.

Treatment:

Drug: Placebo

Drug: Dupilumab

Part B: Dupilumab or Placebo

Experimental group

Description:

Part B consists of a 24-week double-blind treatment period. Participants will be randomized to receive dupilumab dosing regimen 1, dupilumab dosing regimen 2 or placebo. At the end of the double-blind treatment visit (week 24), eligible participants may enter Part C. Participants who do not enter Part C will enter a 12-week follow-up period.

Treatment:

Drug: Placebo

Drug: Dupilumab

Part C: Dupilumab

Experimental group

Description:

Part C is a 28-week extended active treatment period. Participants will receive dupilumab dosing regimen 1, dupilumab dosing regimen 2. At the end of the treatment period (week 52), participants will enter a 12-week follow-up period.

Treatment:

Drug: Dupilumab