Peanut Oral Immunotherapy in Children (IMPACT)

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

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.

Study Overview

• Status: Completed
• Conditions: Peanut Hypersensitivity
• Intervention / Treatment: Biological: Peanut Oral Immunotherapy - Liquid Extract; Biological: Peanut Oral Immunotherapy - Peanut Flour; Biological: Placebo for Peanut Oral Immunotherapy - Liquid Extract form; Biological: Placebo for Peanut Oral Immunotherapy - Peanut Flour

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 Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • University of Arkansas for Medical Sciences: Arkansas Children's Hospital
  • California
    • Stanford, California, United States, 94040
      • Stanford University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Chapel-Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Immune Tolerance Network (ITN)
• Investigators: Study Chair: Wesley Burks, MD, UNC Chapel-Hill; Study Chair: Stacie M. Jones, MD, University of Arkansas

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website
• Immune Tolerance Network website
• ITN IMPACT Study website

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2013
• Primary Completion (Actual): July 2, 2018
• Study Completion (Actual): December 21, 2018

Study Registration Dates

• First Submitted: May 23, 2013
• First Submitted That Met QC Criteria: May 29, 2013
• First Posted (Estimate): June 4, 2013

Study Record Updates

• Last Update Posted (Actual): March 16, 2020
• Last Update Submitted That Met QC Criteria: February 26, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Hypersensitivity; Immunotherapy; Allergy, Peanut; Peanut allergy; Desensitization, Immunologic
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity; Physiological Effects of Drugs; Immunologic Factors
• Other Study ID Numbers: DAIT ITN050AD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No