Clinical trial NCT03682770: Study in Pediatric Subjects With Peanut Allergy to Evaluate Efficacy and Safety of Dupilumab as Adjunct to AR101 (Peanut Oral Immunotherapy)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Peanut Allergy
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
name: Aimmune Therapeutics, Inc.
First posted: 2018-09-25
Enrollment: 148
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Up-dosing Double-blind, Placebo-controlled Food Challenge (DBPCFC) With 2044 mg (Cumulative) Peanut Protein at Visit 16 (Week 28 to 40)
timeFrame: At Visit 16 (Week 28 to 40)
Secondary outcomes:
measure: Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 16 (Week 28 to 40) in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101
timeFrame: Baseline, Visit 16 (Week 28 to 40)
measure: Percentage of Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Reached the 300 mg/Day Dose of AR101 by Visit 16 (Week 28 to 40)
timeFrame: At Visit 16 (Week 28 to 40)
measure: Time From Randomization to the First Time When Participants Reached the 300 mg/Day Dose of AR101 During the Up-dosing Treatment Phase by Visit 16 (Week 28 to 40)
timeFrame: At Visit 16 (Week 28 to 40)
measure: Percentage of Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64)
timeFrame: At Visit 22 (Week 52 to 64)
measure: Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101
timeFrame: Baseline, Visit 22 (Week 52 to 64)
measure: Percentage of Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101 Who Passed a Post Maintenance DBPCFC With 2044 mg (Cumulative) Peanut Protein at Visit 22 (Week 52 to 64)
timeFrame: At Visit 22 (Week 52 to 64)
measure: Change From Baseline in Cumulative Tolerated Dose (Log Transformed) of Peanut Protein During a DBPCFC at Visit 22 (Week 52 to 64) in Participants (Previously) Treated With Dupilumab + AR101/Placebo +AR101 vs Placebo Plus AR101
timeFrame: Baseline, Visit 22 (Week 52 to 64)
measure: Percent Change From Baseline in Peanut-specific IgE in Participants Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 16 (Week 28 to 40)
timeFrame: Baseline up to Visit 16 (Weeks 28 to 40)
measure: Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 22 (Week 52 to 64)
timeFrame: Baseline up to Visit 22 (Week 52 to 64)
measure: Percent Change From Baseline in Peanut-specific IgE in Participants (Continuously) Treated With Dupilumab Plus AR101 vs Placebo Plus AR101 to Visit 25 (Weeks 64 to 76)
timeFrame: Baseline up to Visit 25 (Weeks 64 to 76)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Regeneron Investigational Site
state: Alabama
city: Tucson
country: United States
facility: Regeneron Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Regeneron Investigational Site
state: Arkansas
city: Los Angeles
country: United States
facility: Regeneron Investigational Site
state: California
city: Los Angeles
country: United States
facility: Regeneron Investigational Site
state: California
city: Mission Viejo
country: United States
facility: Regeneron Investigational Site
state: California
city: Mountain View
country: United States
facility: Regeneron Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: Regeneron Investigational Site
state: California
city: Denver
country: United States
facility: Regeneron Investigational Site
state: Colorado
city: Washington
country: United States
facility: Regeneron Investigational Site
state: District of Columbia
city: Tampa
country: United States
facility: Regeneron Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Regeneron Investigational Site
state: Georgia
city: Marietta
country: United States
facility: Regeneron Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Regeneron Investigational Site
state: Illinois
city: Baltimore
country: United States
facility: Regeneron Investigational Site
state: Maryland
city: Boston
country: United States
facility: Regeneron Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Regeneron Investigational Site
state: Michigan
city: Ypsilanti
country: United States
facility: Regeneron Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Regeneron Investigational Site
state: Minnesota
city: Ocean Township
country: United States
facility: Regeneron Investigational Site
state: New Jersey
city: Great Neck
country: United States
facility: Regeneron Investigational Site
state: New York
city: New York
country: United States
facility: Regeneron Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: Regeneron Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: Regeneron Investigational Site
state: Pennsylvania
city: Seattle
country: United States
facility: Regeneron Investigational Site
state: Washington
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: