Dupilumab and Milk OIT for the Treatment of Cow's Milk Allergy

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dupilumab and Milk Oral Immunotherapy for the Treatment of Patients With Cow's Milk Allergy

This is a phase 2, multicenter, randomized, double-blind, parallel group, 2 arm study in approximately 40 subjects aged 4 to 50 years, inclusive, who are allergic to cow's milk. The primary objective is to assess whether dupilumab as an adjunct to milk oral immunotherapy (OIT) compared to placebo improves the safety of milk OIT and rates of desensitization, defined as an increase in the proportion of subjects who pass a double-blind placebo-controlled food challenge (DBPCFC) to at least 2040 mg cumulative milk protein at week 18.

Study Overview

• Status: Recruiting
• Conditions: Allergies Food Milk
• Intervention / Treatment: Drug: Dupilumab; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrew Long, PharmD; Phone Number: 650-521-7237; Email: snpcenterallergy_scheduler@stanford.edu

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Children's Hospital
      • Contact: Benjamin Wright, MD; Phone Number: 480-301-4284; Email: wright.benjamin@mayo.edu
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic
      • Contact: Benjamin Wright, MD; Phone Number: 480-301-4284; Email: wright.benjamin@mayo.edu
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Sean N. Parker Center for Allergy & Asthma Research at Stanford University
      • Contact: Sayantani Sindher, MD; Phone Number: 650-521-7237; Email: snpcenterallergy_scheduler@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 4 to 50 years (inclusive)
• Clinical history of allergy to cow's milk or milk-containing foods
• Serum IgE to milk of >4 kUA/L within the last 12 months and/or a SPT to milk ≥6 mm compared to a negative control
• Experience clinical reaction at or before 444 mg cumulative protein dose of cow's milk protein on Screening DBPCFC
• No clinical reaction observed during the placebo (oat) Screening DBPCFC
• Subjects 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
• Use of effective birth control by female participants of childbearing potential

Exclusion Criteria:

• Any previous exposure to dupilumab
• Known hypersensitivity to dupilumab or any of its excipients
• Known hypersensitivity to epinephrine or any of its excipients
• Allergy to oat (placebo in DBPCFC)
• History of severe anaphylaxis to cow's milk, defined as neurological compromise or requiring intubation
• Recent history of frequent severe, life-threatening episodes of anaphylaxis or anaphylactic shock as defined as 3 or more episodes of anaphylaxis within the past year
• Inability to tolerate biological (antibody) therapies
• Body weight <5 kg at the time of screening
• History of eosinophilic esophagitis (EoE), other eosinophilic gastrointestinal disease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD), symptoms of dysphagia (e.g., difficulty swallowing, food "getting stuck"), or recurrent gastrointestinal symptoms of undiagnosed etiology
• History of cardiovascular disease, including uncontrolled or inadequately controlled hypertension
• History of a mast cell disorder
• Established diagnosis of a primary immunodeficiency disorder
• Severe asthma or mild or moderate asthma if uncontrolled or difficult to control
• Current participation or within the last 4 months in any other interventional study
• Use of medication such as beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) or calcium channel blockers
• Pregnant or breastfeeding women

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dupilumab; 24-week treatment period, which includes a 4-week run-in period with dupilumab followed by 12 weeks of treatment with dupilumab in combination with a gradual up-dosing of milk protein OIT, then followed by 8 weeks of milk OIT dosing with no dupilumab	Drug: Dupilumab; Dupilumab injected every 2 weeks for 18 weeks
Placebo Comparator: Placebo; 24-week treatment period, which includes a 4-week run-in period with placebo for dupilumab followed by 12 weeks of treatment with placebo for dupilumab in combination with a gradual up-dosing of milk protein OIT, then followed by 8 weeks of milk OIT dosing with no placebo	Other: Placebo; Placebo injected every 2 weeks for 18 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects treated with dupilumab plus milk protein OIT vs placebo plus milk protein OIT who tolerate at least 2040 mg (cumulative) cow's milk protein during DBPCFC to milk at week 18	DBPCFC is a double-blind, placebo-controlled food challenge	Week 18

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants who tolerate at least 1040 mg cumulative milk protein at week 18 DBPCFC	Week 18
Proportion of participants who tolerate 4040 mg cumulative milk protein at week 18 DBPCFC	Week 18
Proportion of participants who tolerate at least 1040 mg cumulative milk protein at week 24 DBPCFC	week 24
Proportion of participants who tolerate at least 2040 mg cumulative milk protein at week 24 DBPCFC	Week 24
Proportion of participants who tolerate 4040 mg cumulative milk protein at week 24 DBPCFC	Week 24
Change in the cumulative tolerated dose (CTD) of milk protein during DBPCFC from baseline to week 18 across cohorts as pairwise comparisons of all treatment groups	Baseline and week 18
Change in the cumulative tolerated dose (CTD) of milk protein during DBPCFC from baseline to week 24 across cohorts as pairwise comparisons of all treatment groups	Baseline and week 24

Collaborators and Investigators

• Sponsor: Andrew J Long, PharmD
• Collaborators: Regeneron Pharmaceuticals; Robert Levin Charitable Fund
• Investigators: Study Director: Andrew Long, PharmD, Stanford, Sean N. Parker Center for Allergy & Asthma Research

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Food allergy; Oral Immunotherapy; Milk allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Milk Hypersensitivity
• Other Study ID Numbers: IRB-52976

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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