Study to Evaluate Dupilumab Monotherapy in Pediatric Patients With Peanut Allergy

Study Overview
=================
Brief Summary
-----------------
The primary objective of the study is to assess the tolerability of peanut protein in pediatric patients (6-17 years old) treated with dupilumab monotherapy, in which tolerability is defined as the proportion of patients who safely pass a double-blind placebo-controlled food challenge (DBPCFC) at week 24. The secondary objectives are: To determine whether dupilumab treatment improves peanut tolerability, defined as a change in the cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC To evaluate the safety and tolerability of dupilumab treatment in peanut allergic patients To evaluate the effects of dupilumab treatment on the levels of peanut-specific Immunoglobulin E (IgE) To evaluate the treatment effect of dupilumab on the average wheal size after a titrated skin prick test (SPT), as measured by area under curve (AUC) of the average wheal size induced by peanut extract at different concentrations To assess the incidence of treatment-emergent anti-drug antibodies (ADA) to dupilumab in patients over time

Official Title
-----------------
A Study to Evaluate the Efficacy and Safety of Dupilumab Monotherapy in Pediatric Patients With Peanut Allergy

Conditions
-----------------
Peanut Allergy

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Patient has a clinical history of allergy to peanuts or peanut-containing foods (symptom[s] of reaction due to exposure). Experience dose-limiting symptoms at or before the challenge dose of peanut protein on screening DBPCFC conducted in accordance with Practical Issues in Allergology, Joint United States/European Union Initiative (PRACTALL) guidelines. And not experiencing dose limiting symptoms to placebo Serum IgE to peanut of ≥10 kilo units (kUA)/L and/or a SPT to peanut ≥8 mm compared to a negative control Patients/legal guardians must be trained on the proper use of the epinephrine autoinjector device to be allowed to enroll in the study Patients 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: Any previous exposure to marketed dupilumab or dupilumab in a clinical trial Member of the clinical site study team or his/her immediate family History of other chronic disease (other than asthma, AD, or allergic rhinitis) requiring therapy History of frequent or recent severe, life-threatening episode of anaphylaxis or anaphylactic shock as defined by more than 3 episodes of anaphylaxis within the past year and/or an episode of anaphylaxis within 60 days of screening DBPCFC History of eosinophilic gastrointestinal disease History of eosinophilic granulomatosis with polyangiitis Severe, unstable asthma at time of enrollment or any patient with Forced Expiratory Volume in 1 Second (FEV1) <80% of predicted or asthma control questionnaire (ACQ)>1.5 Use of systemic corticosteroids within 2 months prior to screening Note: Other protocol Inclusion/Exclusion Criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 17 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dupilumab<br>Open label weight base subcutaneous (SC) injection every two (Q2) weeks. | Drug: Dupilumab<br>* Dupilumab weight-based dosing will be administered subcutaneously (SC) in a single-use, pre-filled syringe every two weeks (Q2W)<br>* Other names: SAR231893;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 444 mg (Cumulative) Peanut Protein at Week 24 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, 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 who passed the DBPCFC with at least 444 mg (cumulative) peanut protein at Week 24 was reported. | At Week 24 | 

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 Weeks 24 and 36 | Change from baseline in cumulative tolerated dose (log transformed) of peanut protein during a DBPCFC at Week 24 and Week 36 was reported. | Weeks 24 and 36 | 
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 444 mg (Cumulative) Peanut Protein at Week 36 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, 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. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC. | At Week 36 | 
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 1044 mg (Cumulative) Peanut Protein at Week 24 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, 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 who passed a DBPCFC with at least 1044 mg (cumulative) peanut protein at Week 24 was reported. | At Week 24 | 
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 1044 mg (Cumulative) Peanut Protein at Week 36 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, 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. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC. | At Week 36 | 
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 2044 mg (Cumulative) Peanut Protein at Week 24 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, 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 who passed a DBPCFC with at least 2044 mg (cumulative) peanut protein at Week 24 was reported. | At Week 24 | 
| Percentage of Participants Treated With Dupilumab Who Passed a DBPCFC With at Least 2044 mg (Cumulative) Peanut Protein at Week 36 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, 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. Only participants treated with dupilumab who passed at least 444 mg (cumulative) peanut challenge at Week 24 were eligible for Week 36 DBFC. | At Week 36 | 
| Percent Change From Baseline in Peanut-specific Immunoglobulin E (sIgE) at Weeks 4, 8, 12, 16, 24, and 36 | Percent change from baseline in sIgE at Weeks 4, 8, 12, 16, 24, and 36 was reported. | Weeks 4, 8, 12, 16, 24, and 36 | 
| Change From Baseline in Titrated Skin Prick Test (SPT) Measured by Average Wheal Size Area Under the Curve (AUC) After Peanut Allergen Stimulation at Different Concentrations at Weeks 4, 12, 24, and 36 | The titrated SPT is the skin testing for atopic response at different concentrations of peanut extract with saline as negative control and histamine as positive controls. Wheal size induced by peanut extract at each concentration was calculated as average of largest diameter and perpendicular midpoint diameter. The AUC for titrated SPT was calculated using the mean wheal diameter versus the concentration at which the wheal diameter was measured, which was then normalized to concentration. Change from baseline in titrated SPT as measured by average wheal size AUC after peanut allergen stimulation at different concentrations at Weeks 4, 12, 24, and 36 was reported. | Weeks 4, 12, 24, and 36 | 
| Percentage of Participants With Grade 2 or Above Allergic Reactions During the DBPCFC at Week 24 | Symptoms considered to be allergic were graded using the Consortium of Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions. The scale is Grade 1 (Mild) through 5, the higher the grade, the more severe the allergic reaction. Percentage of participants with Grade 2 (Moderate) or above allergic reactions during the DBPCFC at Week 24 was reported. | At Week 24 | 
| Percentage of Participants Who Used Epinephrine as a Rescue Medication During the DBPCFC at Week 24 | Percentage of participants who used Epinephrine as a rescue medication during the DBPCFC at Week 24 was reported. | At Week 24 |