Challenging to Food With Escalating Thresholds for Reducing Food Allergy
Overview
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Scott Sicherer
- Enrollment
- 73
- Locations
- 1
- Primary Endpoint
- Percentage of Children That Tolerate the Full Challenge
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
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
Eligibility Criteria
- Ages
- 4 Years to 14 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Treatment
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.
Intervention: Peanut Protein (Biological)
Avoidance
Avoids peanut, standard care
Intervention: Continued peanut avoidance (Other)
Outcomes
Primary Outcomes
Percentage of Children That Tolerate the Full Challenge
Time Frame: 72 weeks
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.
Secondary Outcomes
- 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)
- Mean Change in Peanut-specific IgG4(Baseline and 72 weeks)
Investigators
Scott Sicherer
Professor
Icahn School of Medicine at Mount Sinai