Peanut Oral Immunotherapy in Children

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, multi-center study comparing peanut oral immunotherapy (OIT) to placebo in the induction of tolerance and desensitization in peanut-allergic children. Eligible participants with peanut allergy will be randomly assigned to receive either peanut OIT or placebo for 134 weeks followed by peanut avoidance for 26 weeks.

Detailed Description
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An initial oral food challenge (OFC) to 1 g of peanut flour (500 mg peanut protein) will be conducted. Participants must have a clinical reaction during this OFC to initiate study dosing. After the initial OFC, the study design includes four phases: Initial dose escalation (1 day): Peanut or placebo dosing will be given incrementally and increase every 20 minutes until a dose of 12 mg peanut flour (6 mg peanut protein) or placebo flour is given. Build-up (30 weeks): Initial observed dose administration of highest tolerated dose, followed by daily OIT at home with return visit every 2 weeks for dose escalation. Maintenance (104 weeks):The participant will continue on daily OIT with return visits every 13 weeks. At the end of this phase the participant will undergo a blinded OFC to 10 g peanut flour (5 g peanut protein). Avoidance (26 weeks): In this final phase participants will be seen every 13 weeks. At the completion of this phase participants will have a final blinded OFC to 10g peanut flour (5 g peanut protein).

Official Title
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Oral Immunotherapy for Induction of Tolerance and Desensitization in Peanut-Allergic Children (ITN050AD)

Conditions
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Peanut Hypersensitivity

Intervention / Treatment
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* Biological: Peanut Oral Immunotherapy - Liquid Extract
* Biological: Placebo for Peanut Oral Immunotherapy - Liquid Extract form
* Biological: Peanut Oral Immunotherapy - Peanut Flour
* Biological: Placebo for Peanut Oral Immunotherapy - Peanut Flour


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical history of peanut allergy or avoidance of peanut without ever having eaten peanut; Serum immunoglobulin E (IgE) to peanut of ≥5 kUA/L determined by UniCAP™, an in-vitro test system for diagnosis and monitoring of allergy and inflammation; Wheal ≥ 3mm on skin prick test to peanut extract compared to a negative control; A clinical reaction at or below ingestion of 1 g peanut flour (500 mg peanut protein) during screening OFC; Written informed consent from parent/guardian. Exclusion Criteria: History of severe anaphylaxis with hypotension to peanut; Documented clinical history of allergy to oat; Suspected allergy to oat and a wheal ≥7mm on skin prick test to oat extract compared to a negative control; Chronic disease other than asthma, atopic dermatitis, rhinitis requiring therapy; e.g., heart disease or diabetes; Active eosinophilic gastrointestinal disease in the past 2 years; Participation in any interventional study for the treatment of food allergy in the 6 months prior to visit -1; Inhalant allergen immunotherapy that has not yet reached maintenance dosing; Severe asthma, as indicated by repeated hospitalizations or hospital emergency department visits; Moderate asthma defined according to National Asthma Education and Prevention Program Expert; Panel that requires more than fluticasone 440 mcg or its equivalent daily for adequate control; Inability to discontinue antihistamines for skin testing, OFC and the initial dose escalation; Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) in the 12 months prior to visit -1; Any systemic therapy which in the judgment of the investigator could be immunomodulatory (e.g. rituximab) in the 12 months prior to visit -1, systemic corticosteroid therapy of up to a total of three weeks is allowed; Use of any investigational drug in 90 days prior to visit -1; Plan to use any investigational drug during the study period; The presence of any medical condition that the investigator deems incompatible with participation in the trial.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 48 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peanut Oral Immune Therapy (OIT)<br>Peanut OIT for 134 weeks followed by peanut avoidance for 26 weeks. | Biological: Peanut Oral Immunotherapy - Liquid Extract<br>* Used during initial dose escalation for doses 0.1 to 0.8 mg.<br>Biological: Peanut Oral Immunotherapy - Peanut Flour<br>* This will be used for the remainder of dose escalation, build-up, and maintenance.<br>|
| Placebo Comparator: Peanut Placebo<br>Peanut placebo for 134 weeks followed by peanut avoidance for 26 weeks. The placebo extract will be derived from oat flour source material. | Biological: Placebo for Peanut Oral Immunotherapy - Liquid Extract form<br>* Similar in appearance, texture, and taste to peanut liquid extract.<br>Biological: Placebo for Peanut Oral Immunotherapy - Peanut Flour<br>* Similar in appearance, texture, and taste to peanut flour.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT) | Definition of desensitized to peanut: A participant who passed the blinded (masked) oral food challenge (OFC) to10 grams of peanut flour (=5 grams of peanut protein) without significant symptoms.* *Significant symptoms include hives, wheezing, vomiting, or laryngeal edema. | Week 134 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Tolerant Participants at Week 160 | Definition of Tolerant: A participant who passed the oral food challenge (OFC) to 10 grams of peanut flour (=5 grams of peanut protein). | Week 160 | 
| Count of Participants With Transient Desensitization | Definition of transient desensitization: A participant who passed the blinded (masked) oral food challenge (OFC) to 10 grams peanut flour (=5 grams peanut protein) at week 134 and failed the week 160 in the Peanut oral immunotherapy (OIT) group. | Week 134, Week 160 | 
| Highest Tolerated Cumulative Dose | The highest tolerated cumulative dose of peanut protein during the blinded (masked) oral food challenge (OFC) at Week 160, analyzed within and between both placebo and peanut OIT groups. The highest cumulative dose of peanut protein tolerated for each participant was analyzed as a continuous outcome. Any randomized participant without an evaluable blinded (masked) OFC was imputed as not tolerant. For the continuous highest cumulative dose endpoint, this is defined as having a highest cumulative dose imputed as zero. | Week 160 | 
| Percentage of Participants That Withdrew From the Study | Percentage of participants that withdrew from study participation, listed by study phase (at time of study withdrawal). | Initial Dose Escalation through Week 160 (Tolerance Assessment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allergy, Peanut, Peanut allergy, Hypersensitivity, Immunotherapy, Desensitization, Immunologic