Immune Basis and Clinical Implications of Threshold-based Phenotypes of Peanut Allergy

NCT03907397 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GCO 17-0722U19AI136053
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine whether allowing ingestion of sub-threshold amounts of peanut in those with a high threshold (tolerate at least 143 mg peanut protein on supervised double-blind, placebo-controlled oral food challenge \[DBPCFC\]) will be associated with attaining even higher thresholds over time in children with high threshold peanut allergy compared to those avoiding peanut. The secondary clinical objectives include assessing the development of sustained unresponsiveness (SU, a surrogate term for tolerance without daily ingestion), effects on quality of life, and safety compared to those avoiding peanut. Additionally, this study will phenotype the allergic response to peanut based on threshold and response to exposure. Mechanistic study objectives will determine the immune and molecular basis of the high threshold endotype, identify predictors of response to exposure, and determine mechanisms and biomarkers of remission.

Conditions

Food Allergy; Peanut Allergy

Keywords

allergy; food; peanut; threshold; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Children That Tolerate the Full Challenge

  The difference between the treatment and comparison (avoidance) groups in the percentage of children who by the endpoint double-blind, placebo-controlled oral food challenge (DBPCFC) tolerate a dose at least 2 steps higher than their baseline DBPCFC or 9043 mg of peanut protein. Due to missing data in the primary endpoint, the protocol \& SAP specified a priori that missing data would be imputed using multiple imputation and results based on 30 completed-imputed data sets would be combined using Rubin's rule. In the Peanut Protein group, the observed data was so strong that participants with missing data were also imputed as success across all imputations (hence, 100% success rate). In the Peanut Avoidance group, there was more variability in the proportion of successes across imputations and these varying proportions were averaged. Missing data were imputed and results were pooled.

  72 weeks

Secondary Outcomes (6)

• The Percentage of Children That Achieve Sustained Unresponsiveness

  96 weeks

• Number of Children With Acute Allergic Reactions

  96 weeks

• Mean Change in Food Allergy Quality of Life Parental Burden Instrument

  baseline and at 72 weeks

• Mean Change in SPT Wheal Size

  Baseline and 72 weeks

• Mean Change in Peanut-specific IgE

  Baseline and 72 weeks

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Ingests peanut - . Depending upon reaction threshold, participants may begin with different starting amounts of store bought peanut butter measured with study-supplied kitchen measuring spoons.

Biological: Peanut Protein

Avoidance

OTHER

Avoids peanut, standard care

Other: Continued peanut avoidance

Interventions

Peanut Protein BIOLOGICAL

up to 3 level teaspoons peanut butter or equivalent (approximately 3400 mg)

Treatment

Continued peanut avoidance OTHER

Standard of care avoidance of peanut

Avoidance

Eligibility Criteria

• Age: 4 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject and/or parent guardian must be able to understand and provide informed consent.
• Age 4-14 years
• either sex
• any race, any ethnicity
• who are enrolled while strictly avoiding peanut
• have a history of sensitization (detectable peanut IgE \>0.35 kUA/L)
• On screening DBPCFC are able to ingest \>= 143 mg peanut protein but \< 5043 mg peanut protein.
• All children will have documented consent and assent as is appropriate for age.

You may not qualify if:

• Individuals who meet any of these criteria are not eligible for enrollment as study participants:
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• Serum peanut-specific IgE antibody level \> 50 kUA/L
• Recent (within the past 2 years) life-threatening (grade 3) anaphylactic reaction to peanut.
• Any disorder in which epinephrine is contraindicated such as known hypertension or cardia rhythm disorders.
• History of chronic disease requiring therapy (other than asthma, atopic dermatitis, rhinitis).
• On a build-up phase of any allergen immunotherapy.
• FEV1 value \<80% predicted (only for participants age 7 years or older and are able to perform spirometry)
• ACT or cACT \< 20
• \>Step 3 controller therapy as defined for children 0-4, 5-11 and \>=12 years of age by EPR-3 tables
• Use of steroid medications in the following manners:
• history of daily oral steroid dosing for \>1 month during the past year,
• having 1 burst or steroid course within the past 6 months, or
• having \>1 burst oral steroid course within the past 12 months.
• Asthma requiring \>1 hospitalization in the past year for asthma or \>1 ED visit in the past 6 months for asthma, or any prior intubation/mechanical ventilation for asthma/wheezing.

Sponsors & Collaborators

• Scott Sicherer: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• Sicherer SH, Bunyavanich S, Berin MC, Lo T, Groetch M, Schaible A, Perry SA, Wheatley LM, Fulkerson PC, Chang HL, Suarez-Farinas M, Sampson HA, Wang J. Peanut Oral Immunotherapy in Children with High-Threshold Peanut Allergy. NEJM Evid. 2025 Mar;4(3):EVIDoa2400306. doi: 10.1056/EVIDoa2400306. Epub 2025 Feb 10.

  PMID: 39928078 DERIVED

MeSH Terms

Conditions

Food Hypersensitivity; Peanut Hypersensitivity; Hypersensitivity

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Immune System Diseases; Nut and Peanut Hypersensitivity

Results Point of Contact

• Title: Dr. Scott Sicherer
• Organization: Icahn School of Medicine at Mount Sinai

scott.sicherer@mssm.edu

212-241-5548

Study Officials

• Scott Sicherer, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Although a double-blind, placebo controlled oral food challenge test is used in screening to identify participants eligible to continue to randomization in the study, those randomized to peanut ingestion versus avoidance have participants aware and unmasked regarding the study arm to which they were randomized
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 150-200 children undergoing DBPCFC to peanut to identify 72 with high threshold peanut allergy for randomization in trial.

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: April 9, 2019
• Study Start: August 5, 2019
• Primary Completion: November 17, 2023
• Study Completion: November 17, 2023
• Last Updated: February 7, 2025
• Results First Posted: February 7, 2025

Record last verified: 2025-02

Locations

US (1)