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

Study Overview
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Brief Summary
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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.

Official Title
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Challenging to Food With Escalating Thresholds for Reducing Food Allergy

Conditions
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Food Allergy, Peanut Allergy

Intervention / Treatment
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* Biological: Peanut Protein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Subject and/or parent guardian must be able to understand and provide informed consent. Inclusion criteria for screening DBPCFC: 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) Inclusion criteria for randomization: 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. Exclusion Criteria: 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. For those with a history of asthma, the following are assessed and any of the following is an exclusion (markers of current uncontrolled or moderate to severe asthma): 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. Gastrointestinal eosinophilic disorders, esophagitis, gastroenteritis. Use of short-acting antihistamines (diphenhydramine, etc.) more than one time within 3 days prior to DBPCFC or skin testing.* Use of medium-acting antihistamines (hydroxyzine, loratadine, etc.) more than one time within 7 days of DBPCFC or skin testing.* Use of systemic steroid medications (IV, IM or oral) for indications other than asthma for > 3 weeks within the past 6 months Use of beta-blockers (oral), (ACE) inhibitors, angiotensin-receptor blockers or calcium channel blockers. Participation in any trials of therapeutic interventions for food allergy in the past year. Therapy with anti-IgE or other biologics, including within 1 year of enrollment. Use of investigational drugs within 52 weeks of participation. Allergy to all of the following: oat, rice, corn, tapioca. Pregnancy Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. *Any subject meeting these criteria during the visits can be rescheduled for the oral food challenge or prick skin testing.*

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 14 Years

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
Interventional Model Description: 200-250 children undergoing DBPCFC to peanut to identify 72 with high threshold peanut allergy for randomization in trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment<br>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<br>* up to 9043 mg<br>|
| No Intervention: Avoidance<br>Avoids peanut, standard care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in the percentage of children that tolerate the full challenge | The difference in the percentage of children who by the endpoint DBPCFC tolerate a dose at least 2 steps higher than their baseline DBPCFC or 9043 mg of peanut protein as compared to baseline | up to 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of children that achieve sustained unresponsiveness | The percentage of children who achieve sustained unresponsiveness or natural tolerance during the study. | up to 96 weeks | 
| Number of acute allergic reactions | Safety parameter assessed by number of acute allergic reactions which includes anaphylaxis or gastrointestinal side effects. | up to 96 weeks | 
| Food Allergy Quality of Life Parental Burden Instrument | The Food Allergy Quality of Life-Parental Burden (FAQL-PB) Scale is a 17-item instrument. It utilizes a 7-point Likert scale ranging from 0 (not troubled) to 6 (extremely troubled). The number circled for each question is summed to provide a total continuous score with a higher score indicating greater burden on the family. Scores can range from 0 to 102 or can be divided by 17 to obtain a mean total score from 0 to 6. | up to 72 weeks | 
| Change in SPT wheal size | Change in Skin Prick Test (SPT) mean wheal size at 72 weeks as compared to baseline. | baseline and 72 weeks | 
| Change in Peanut-specific IgE | Changes in Peanut-specific IgE level at week 72 as compared to baseline. | baseline and 72 weeks | 
| Change in Peanut-specific IgG4 | Changes in Peanut-specific IgG4 level at week 72 as compared to baseline. | baseline and 72 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allergy, food, peanut, threshold, immunotherapy