Study in Pediatric Subjects With Peanut Allergy to Evaluate Efficacy and Safety of Dupilumab as Adjunct to AR101 (Peanut Oral Immunotherapy)

Study Overview
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Brief Summary
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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

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Study in Pediatric Subjects With Peanut Allergy to Evaluate the Efficacy and Safety of Dupilumab as Adjunct to AR101 (Peanut Oral Immunotherapy)

Conditions
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Peanut Allergy

Intervention / Treatment
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* Drug: Dupilumab
* Drug: Placebo matching dupilumab
* Drug: AR101


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dupilumab + AR101<br>Participant randomization of a ratio of 2 active dupilumab arms | Drug: Dupilumab<br>* Dupilumab will be administered subcutaneously (SC) in a single-use, pre-filled glass syringe every two weeks (Q2W)<br>Drug: AR101<br>* AR101 will be provided in dose-escalating capsules and then sachets during maintenance phase<br>|
| Experimental: placebo matching dupilumab + AR101<br>Participant randomization of a ratio of 1 placebo arm | Drug: Placebo matching dupilumab<br>* Placebo matching dupilumab is prepared in the same formulation without the addition of protein<br>Drug: AR101<br>* AR101 will be provided in dose-escalating capsules and then sachets during maintenance phase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants treated with dupilumab plus AR101 vs placebo plus AR101 who pass a post up-dosing double-blind, placebo-controlled food challenge (DBPCFC) with 2044 mg (cumulative) peanut protein |  | Up to 40 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC in participants treated with dupilumab plus AR101 vs placebo plus AR101 |  | Up to 40 weeks | 
| Proportion of participants treated with dupilumab plus AR101 vs placebo plus AR101 who reach the protocol defined dose of AR101 |  | Up to 40 weeks | 
| Time from randomization to the first time when participants reach the protocol defined dose of AR101 |  | Up to 40 weeks | 
| Proportion of participants (continuously) treated with dupilumab plus AR101 vs placebo plus AR101 who pass a post maintenance DBPCFC with 2044 mg (cumulative) peanut protein |  | Up to 64 weeks | 
| Change in the cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC in participants (continuously) treated with dupilumab plus AR101 vs placebo plus AR101 |  | Up to 64 weeks | 
| Proportion of participants (previously) treated with dupilumab plus AR101 (and re-randomized to placebo plus AR101) vs placebo plus AR101 who pass a post maintenance DBPCFC with 2044 mg (cumulative) peanut protein |  | Up to 64 weeks | 
| Change in the cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC in participants (previously) treated with dupilumab plus AR101 (and re-randomized to placebo plus AR101) vs placebo plus AR101 |  | Up to 64 weeks | 
| Percent change in peanut-specific Immunoglobulin E (IgE) in participants treated with dupilumab plus AR101 vs participants treated placebo plus AR101 |  | Up to 40 weeks | 
| Percent change in peanut-specific IgE in participants (continuously) treated with dupilumab plus AR101 vs participants treated placebo plus AR101 |  | Up to 64 weeks | 
| Percent change in peanut-specific IgE in participants (continuously) treated with dupilumab plus AR101 vs participants treated placebo plus AR101 |  | Up to 76 weeks | 
| Proportion of participants experiencing allergic symptoms by treatment group measured by the daily symptom e-diary | Allergic severity of each symptom will be rated on a scale of 1-10. (1 = Not Bad, 10 = Terribly Bad) | Baseline up to 40 weeks | 
| Mean severity score for each symptom by treatment group measured by the daily symptom e-diary |  | Baseline up to 40 weeks | 
| Maximum severity score for each symptom by treatment group measured by the daily symptom e-diary |  | Baseline up to 40 weeks | 
| Difference in mean/median duration of symptoms by treatment group measured by the daily symptom e-diary |  | Baseline up to 40 weeks |