Peanut Oral Immunotherapy in Children (IMPACT)

• ClinicalTrials.gov Identifier: NCT01867671
• Recruitment Status: Completed
• First Posted: June 4, 2013
• Results First Posted: January 22, 2020
• Last Update Posted: March 16, 2020
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Immune Tolerance Network (ITN)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Peanut Hypersensitivity	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	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 146 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Oral Immunotherapy for Induction of Tolerance and Desensitization in Peanut-Allergic Children (ITN050AD)
• Actual Study Start Date: August 13, 2013
• Actual Primary Completion Date: July 2, 2018
• Actual Study Completion Date: December 21, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Desensitized to Peanut Protein After 134 Weeks of Oral Immunotherapy (OIT) [ Time Frame: 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 :

1. Percentage of Tolerant Participants at Week 160 [ Time Frame: 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).
2. Count of Participants With Transient Desensitization [ Time Frame: 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.
3. Highest Tolerated Cumulative Dose [ Time Frame: 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.

4. Percentage of Participants That Withdrew From the Study [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 12 Months to 48 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arkansas

University of Arkansas for Medical Sciences: Arkansas Children's Hospital

Little Rock, Arkansas, United States, 72202

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94040

United States, Maryland

Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

United States, New York

Mount Sinai School of Medicine

New York, New York, United States, 10029

United States, North Carolina

UNC Chapel-Hill

Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

Investigators

• Study Chair: Wesley Burks, MD; UNC Chapel-Hill
• Study Chair: Stacie M. Jones, MD; University of Arkansas

  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):

Study Protocol and Statistical Analysis Plan  [PDF] March 28, 2017

More Information

Additional Information:

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 

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01867671
• Other Study ID Numbers: DAIT ITN050AD
• First Posted: June 4, 2013
• Results First Posted: January 22, 2020
• Last Update Posted: March 16, 2020
• Last Verified: February 2020

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Allergy, Peanut; Peanut allergy; Hypersensitivity; Immunotherapy; Desensitization, Immunologic

Additional relevant MeSH terms:

Hypersensitivity; Peanut Hypersensitivity; Immune System Diseases; Nut and Peanut Hypersensitivity; Food Hypersensitivity; Hypersensitivity, Immediate; Immunomodulating Agents; Immunologic Factors; Physiological Effects of Drugs