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

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
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

Conditions
-----------------
Allergies Food Milk

Intervention / Treatment
-----------------
* Drug: Dupilumab
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 4 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: dupilumab or placebo arm
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dupilumab<br>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<br>* Dupilumab injected every 2 weeks for 18 weeks<br>|
| Placebo Comparator: Placebo<br>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<br>* Placebo injected every 2 weeks for 18 weeks<br>|

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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Food allergy, Milk allergy, Oral Immunotherapy