Peanut Oral Immunotherapy in Children

Phase 2

Completed

• Conditions: Peanut Hypersensitivity
• Interventions: 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

• Registration Number: NCT01867671
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2013-05-23
• Study First Submitted QC: 2013-05-29
• Study First Posted: 2013-06-04
• Study Start: 2013-08-13
• Primary Completion: 2018-07-02
• Disposition First Submitted: 2018-09-26
• Disposition First Submitted QC: 2018-09-26
• Disposition First Posted: 2018-10-01
• Study Completion: 2018-12-21
• Results First Submitted: 2019-12-20
• Results First Submitted QC: 2020-01-10
• Results First Posted: 2020-01-22
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-26
• Last Update Posted: 2020-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 146

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Peanut Oral Immune Therapy (OIT)	Peanut Oral Immunotherapy - Peanut Flour	Peanut OIT for 134 weeks followed by peanut avoidance for 26 weeks.
Peanut Oral Immune Therapy (OIT)	Peanut Oral Immunotherapy - Liquid Extract	Peanut OIT for 134 weeks followed by peanut avoidance for 26 weeks.
Peanut Placebo	Placebo for Peanut Oral Immunotherapy - Peanut Flour	Peanut placebo for 134 weeks followed by peanut avoidance for 26 weeks. The placebo extract will be derived from oat flour source material.
Peanut Placebo	Placebo for Peanut Oral Immunotherapy - Liquid Extract form	Peanut placebo for 134 weeks followed by peanut avoidance for 26 weeks. The placebo extract will be derived from oat flour source material.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT)	Week 134	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.

Secondary Outcome Measures

Name	Time	Method
Count of Participants With Transient Desensitization	Week 134, Week 160	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.
Highest Tolerated Cumulative Dose	Week 160	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.
Percentage of Tolerant Participants at Week 160	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).
Percentage of Participants That Withdrew From the Study	Initial Dose Escalation through Week 160 (Tolerance Assessment)	Percentage of participants that withdrew from study participation, listed by study phase (at time of study withdrawal).

Trial Locations

Locations (5)

UNC Chapel-Hill; 🇺🇸 Chapel Hill, North Carolina, United States

Mount Sinai School of Medicine; 🇺🇸 New York, New York, United States

Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States

Stanford University School of Medicine; 🇺🇸 Stanford, California, United States

University of Arkansas for Medical Sciences: Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States