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

Peanut Allergy Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03682770
• Other study ID #: R668-ALG-16114
• Status: Completed
• Phase: Phase 2
• Start date: October 3, 2018
• Est. completion date: July 23, 2021

Study information

• Verified date: January 2024
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: July 23, 2021
• Est. primary completion date: October 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Peanut Allergy
• Peanut Hypersensitivity

Intervention

Drug:
• Dupilumab
Dupilumab will be administered subcutaneously (SC) in a single-use, pre-filled glass syringe every two weeks (Q2W)
• Placebo matching dupilumab
Placebo matching dupilumab is prepared in the same formulation without the addition of protein
• AR101
AR101 will be provided in dose-escalating capsules and then sachets during maintenance phase

Locations

Country	Name	City	State
United States	Regeneron Investigational Site	Ann Arbor	Michigan
United States	Regeneron Investigational Site	Atlanta	Georgia
United States	Regeneron Investigational Site	Baltimore	Maryland
United States	Regeneron Investigational Site	Birmingham	Alabama
United States	Regeneron Investigational Site	Boston	Massachusetts
United States	Regeneron Investigational Site	Chapel Hill	North Carolina
United States	Regeneron Investigational Site	Chicago	Illinois
United States	Regeneron Investigational Site	Denver	Colorado
United States	Regeneron Investigational Site	Great Neck	New York
United States	Regeneron Investigational Site	Little Rock	Arkansas
United States	Regeneron Investigational Site	Los Angeles	California
United States	Regeneron Investigational Site	Los Angeles	California
United States	Regeneron Investigational Site	Marietta	Georgia
United States	Regeneron Investigational Site	Minneapolis	Minnesota
United States	Regeneron Investigational Site	Mission Viejo	California
United States	Regeneron Investigational Site	Mountain View	California
United States	Regeneron Investigational Site	New York	New York
United States	Regeneron Investigational Site	Ocean Township	New Jersey
United States	Regeneron Investigational Site	Philadelphia	Pennsylvania
United States	Regeneron Investigational Site	Rolling Hills Estates	California
United States	Regeneron Investigational Site	Seattle	Washington
United States	Regeneron Investigational Site	Tampa	Florida
United States	Regeneron Investigational Site	Tucson	Arizona
United States	Regeneron Investigational Site	Washington	District of Columbia
United States	Regeneron Investigational Site	Ypsilanti	Michigan

Sponsors (3)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Aimmune Therapeutics, Inc., Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)