Dupilumab and Milk OIT for the Treatment of Cow's Milk Allergy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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 [Week 18]
DBPCFC is a double-blind, placebo-controlled food challenge
Secondary Outcome Measures
- 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]
Eligibility Criteria
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 ≤17 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix Children's Hospital | Phoenix | Arizona | United States | 85016 |
| 2 | Mayo Clinic | Scottsdale | Arizona | United States | 85259 |
| 3 | Sean N. Parker Center for Allergy & Asthma Research at Stanford University | Mountain View | California | United States | 94040 |
Sponsors and Collaborators
- Andrew J Long, PharmD
- Robert Levin Charitable Fund
- Regeneron Pharmaceuticals
Investigators
- Study Director: Kari Nadeau, Sean N Parker Center for Allergy & Asthma Research at Stanford
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-52976