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

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)

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

Study Overview

• Status: Completed
• Conditions: Peanut Allergy
• Intervention / Treatment: Drug: Dupilumab; Drug: AR101; Drug: Placebo matching dupilumab

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Regeneron Investigational Site
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Regeneron Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Regeneron Investigational Site
  • California
    • Los Angeles, California, United States, 90027
      • Regeneron Investigational Site
    • Los Angeles, California, United States, 90095
      • Regeneron Investigational Site
    • Mission Viejo, California, United States, 92691
      • Regeneron Investigational Site
    • Mountain View, California, United States, 94040
      • Regeneron Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • Regeneron Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80206
      • Regeneron Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Regeneron Investigational Site
  • Florida
    • Tampa, Florida, United States, 33612
      • Regeneron Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Regeneron Investigational Site
    • Marietta, Georgia, United States, 30144
      • Regeneron Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Regeneron Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Regeneron Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Regeneron Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Regeneron Investigational Site
    • Ypsilanti, Michigan, United States, 48197
      • Regeneron Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Regeneron Investigational Site
  • New Jersey
    • Ocean Township, New Jersey, United States, 07712
      • Regeneron Investigational Site
  • New York
    • Great Neck, New York, United States, 11021
      • Regeneron Investigational Site
    • New York, New York, United States, 10029
      • Regeneron Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Regeneron Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Regeneron Investigational Site
  • Washington
    • Seattle, Washington, United States, 98115
      • Regeneron Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage of participants treated with dupilumab plus AR101 vs placebo plus AR101 who passed a post up-dosing DBPCFC with 2044 mg (Cumulative) peanut protein at Visit 16 (Week 28 to 40) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40).	At Visit 16 (Week 28 to 40)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 28 to Week 40).	Baseline, Visit 16 (Week 28 to 40)
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)	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) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40).	At Visit 16 (Week 28 to 40)
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)	Time (in days) 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) was reported. If participants did not reach the 300 mg/day dose of AR101 during the 28-week treatment period, they were censored at the date of their last visit during pre-AR101 dosing and AR101 up-dosing treatment period. Analysis was performed using Kaplan-Meier Estimated method.	At Visit 16 (Week 28 to 40)
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)	Symptoms considered to be allergic were graded using the CoFAR Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. 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) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64).	At Visit 22 (Week 52 to 64)
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	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 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 52 to Week 64).	Baseline, Visit 22 (Week 52 to 64)
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)	Symptoms considered to be allergic were graded using the CoFAR Grading Scale for Systemic Allergic Reactions. The allergic reaction is measured on a 1-5 scale, with grade 1 being mild, grade 2 being moderate, grade 3 being severe, grade 4 being life threatening, and grade 5 as death. the higher the grade, the more severe the allergic reaction. Participants were considered to have passed the DBPCFC if they did not experience any objective Grade 1 reaction. Percentage 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 at Visit 22 (Week 52 to 64) was reported. Cumulative data during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64).	At Visit 22 (Week 52 to 64)
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	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 plus AR101 (and re-randomized to placebo plus AR101) vs placebo plus AR101 was reported. Cumulative tolerated dose during the specified period was calculated as the mean of all available post-randomization values during the specified time period (Week 52 to Week 64).	Baseline, Visit 22 (Week 52 to 64)
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)	Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 16 (Week 28 to 40) was reported. Analysis was performed using Last observation carried forward (LOCF) method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 28 to Week 40).	Baseline up to Visit 16 (Weeks 28 to 40)
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)	Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 22 (Week 52 to 64) was reported. Analysis was performed using LOCF method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 52 to Week 64).	Baseline up to Visit 22 (Week 52 to 64)
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)	Percent change from baseline in peanut-specific IgE in participants treated with dupilumab + AR101 vs placebo + AR101 to Visit 25 (Week 64 to 76) was reported. Analysis was performed using LOCF method. Data reported during the specified period was calculated as the average of all available post-randomization values during the specified time period (Week 64 to Week 76).	Baseline up to Visit 25 (Weeks 64 to 76)

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Collaborators: Sanofi; Aimmune Therapeutics, Inc.
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2018
• Primary Completion (Actual): October 16, 2020
• Study Completion (Actual): July 23, 2021

Study Registration Dates

• First Submitted: September 21, 2018
• First Submitted That Met QC Criteria: September 21, 2018
• First Posted (Actual): September 25, 2018

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: R668-ALG-16114

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No