Study in Pediatric Subjects With Peanut Allergy to Evaluate Efficacy and Safety of Dupilumab as Adjunct to AR101 (Peanut Oral Immunotherapy)
Condition: Peanut Allergy
MeSH terms: Hypersensitivity; Peanut Hypersensitivity
Intervention: Dupilumab; Placebo matching dupilumab; AR101
Intervention description: Dupilumab will be administered subcutaneously (SC) in a single-use, pre-filled glass syringe every two weeks (Q2W); Placebo matching dupilumab is prepared in the same formulation without the addition of protein; AR101 will be provided in dose-escalating capsules and then sachets during maintenance phase
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 148.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      Primary objective is to assess whether dupilumab as adjunct to AR101 compared to placebo
      improves desensitization at the completion of up-dosing, defined as an increase in the
      proportion of participants who pass a post up-dosing double-blind placebo-controlled food
      challenge (DBPCFC) at visit 16.

      Secondary objectives are:

        -  To assess whether dupilumab as adjunct to AR101 compared to placebo improves
           desensitization at the completion of up-dosing, defined as an increase in the cumulative
           tolerated dose (log transformed) of peanut protein during a post up-dosing DBPCFC at
           visit 16

        -  To assess whether dupilumab as (indefinite [continuously]) adjunct to AR101 compared to
           placebo maintains desensitization, defined as an increase in the proportion of
           participants who pass a post maintenance DBPCFC at visit 22

        -  To assess whether dupilumab as (limited [previously]) adjunct to AR101 compared to
           placebo maintains desensitization, defined as an increase in the proportion of
           participants who pass a post maintenance DBPCFC at visit 22

        -  To evaluate the safety and tolerability of dupilumab as adjunct to AR101 compared to
           placebo

        -  To assess the effect of dupilumab (compared to placebo) as adjunct to AR101 on the
           change in peanut-specific Immunoglobulin E (sIgE), Immunoglobulin G (IgG),
           Immunoglobulin G4 (IgG4), and peanut-specific IgG4/IgE ratio

        -  To assess if dupilumab increases the tolerability of AR101 as measured by the daily
           symptoms (electronic diary [e-diary]) during the up-dosing phase
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Experience dose-limiting symptoms at or before the challenge dose of peanut protein on
             screening and not experiencing dose-limiting symptoms to placebo as defined in the
             protocol

          -  Serum Immunoglobulin E (IgE) to peanut of ≥10 kUA/L and/or a skin prick test (SPT) to
             peanut ≥8 mm compared to a negative control

          -  Participants/legal guardians must be trained on the proper use of the epinephrine
             autoinjector device to be allowed to enroll in the study

          -  Participants with other known food allergies must agree to eliminate these other food
             items from their diet so as not to confound the safety and efficacy data from the
             study

        Key Exclusion Criteria:

          -  History of other chronic disease (other than asthma, Atopic Dermatitis (AD), or
             allergic rhinitis) requiring therapy (eg, heart disease, diabetes, hypertension) that
             would represent a risk to participant's health or safety in this study or ability to
             comply with study protocol

          -  History of frequent or recent severe, life-threatening episode of anaphylaxis or
             anaphylactic shock

          -  History of eosinophilic Gastrointestinal (GI) disease

          -  Asthma at time of enrollment with any of the following:

               -  Forced Expiratory Volume 1 Second (FEV1) <80% of predicted or ratio of FEV1 to
                  forced vital capacity (FEV1/FVC) <75% of predicted with or without controller
                  medications

               -  Inhaled corticosteroids (ICS) dosing of daily fluticasone (or equivalent ICS
                  based on NHLBI dosing chart)

               -  One hospitalization in the past year for asthma

               -  Emergency room visit for asthma within 6 months prior to screening

          -  Use of systemic corticosteroids within 2 months prior to screening

          -  Use of other forms of allergen immunotherapy or immunomodulatory therapy within 3
             months prior to screening

          -  Use of any agents known or likely to interact with epinephrine (eg, beta-blockers,
             angiotensin converting enzyme-inhibitors, tri-cyclic antidepressants, or other drugs),
             within 3 weeks prior to screening

          -  Allergy to oat (placebo in DBPCFC)

        Note: Other protocol Inclusion/Exclusion Criteria apply