Study to Determine the Efficacy and Safety of Dupilumab in Adult and Adolescent Patients With Eosinophilic Esophagitis (EoE)
Condition: Eosinophilic Esophagitis
MeSH terms: Esophagitis; Eosinophilic Esophagitis
Intervention: Dupilumab; Placebo
Intervention description: Solution for injection administered subcutaneously; Matching placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 321.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility 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