A Study of Sublingual Immunotherapy in Peanut-allergic Children

Study Overview
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Brief Summary
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The specific aim of this study is to determine if peanut allergen-specific SLIT will cause clinical desensitization and tolerance to develop in peanut-allergic young children.

Detailed Description
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In spite of increased recognition and understanding of food allergies, food-induced anaphylaxis remains the single most common cause of anaphylaxis seen in hospital emergency departments, accounting for about one third of anaphylaxis cases seen. It is estimated that about 30,000 food-induced anaphylactic events are seen in U.S. emergency departments each year and that about 200 fatal cases occur in the U.S. each year. Either peanuts or tree nuts cause more than 80% of these reactions. No treatments are available and avoidance is the only approved intervention. The goal of this study is to investigate peanut sublingual immunotherapy (SLIT) as a treatment for children with peanut allergy. This study is primarily designed to evaluate the efficacy and safety of peanut SLIT compared to placebo after 12 months. Secondarily, the study is designed to evaluate the efficacy of extended maintenance dosing of peanut SLIT in inducing lasting tolerance after discontinuation of the peanut SLIT. Mechanistic studies will be completed concurrently as exploratory endpoints to understand changes in the allergic immune response related to peanut SLIT.

Official Title
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A Double-blinded, Placebo-controlled Study of Peanut Sublingual Immunotherapy in Children - DBPC Peanut SLIT

Conditions
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Food Hypersensitivity

Intervention / Treatment
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* Drug: Peanut SLIT
* Drug: Placebo SLIT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Peanut IgE > 7kU/L (> 2kU/L for children aged 2 years and under) AND History of significant clinical symptoms within 60 minutes after the ingestion of peanuts. Exclusion Criteria: History of severe life-threatening anaphylaxis to peanut, OR Medical history that would prevent a DBPCFC to peanut, OR Subjects with wheat or oat allergy (which are used in the placebo), OR Unable to cooperate with challenge procedures, OR Unable to be reached by telephone for follow-up

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 11 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: Crossover Assignment
Interventional Model Description: For the initial 12 months of the study, subjects were blinded to receive either peanut SLIT or placebo. After unblinding, subjects on placebo are crossed over to receive open-label peanut SLIT. They underwent an identical dosing protocol as those that were initially randomized to active treatment. After 12 months of peanut SLIT dosing, whether initially randomized to active or crossed over from placebo, all subjects remained part of an open-label extended maintenance phase for the duration of the study (total peanut SLIT dosing 36-60 months) 2 additional cohorts were included in the protocol. One cohort, called the Early Unblinded Peanut SLIT cohort, was unblinded prior to the scheduled 12 month time point for pharmacy safety concerns. The second cohort, called the Pilot Peanut SLIT Rollover cohort involved subjects from the prior pilot study (NCT00429429) who were added to the study through an amendment and received open-label peanut SLIT.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Blinded Peanut SLIT<br>Blinded subjects who received peanut sublingual drops for the initial 12 month blinded phase of the study. | Drug: Peanut SLIT<br>* Liquid peanut protein drops diluted in glycerin which are dosed under the tongue.<br>* Other names: Sublingual peanut protein drops;|
| Placebo Comparator: Blinded Placebo SLIT<br>Blinded subjects who received placebo sublingual drops for the initial 12 month blinded phase of the study. | Drug: Placebo SLIT<br>* Liquid glycerin without peanut which are dosed under the tongue.<br>* Other names: Sublingual glycerin saline drops;|
| Other: Ext. maint. open label peanut SLIT<br>After completing the blinded phase of the study, subjects receiving Blinded Peanut SLIT continued on extended maintenance open-label peanut SLIT for the duration of the study. Subjects receiving Blinded Placebo SLIT were crossed over and underwent the 12 month buildup protocol on open label peanut SLIT and then continued on extended maintenance treatment for the duration of the study. | Drug: Peanut SLIT<br>* Liquid peanut protein drops diluted in glycerin which are dosed under the tongue.<br>* Other names: Sublingual peanut protein drops;|
| Other: Early unblinded peanut SLIT<br>Subjects who were unblinded prematurely during the blinded phase of the study and then re-enrolled as an open label cohort. | Drug: Peanut SLIT<br>* Liquid peanut protein drops diluted in glycerin which are dosed under the tongue.<br>* Other names: Sublingual peanut protein drops;|
| Other: Pilot peanut SLIT rollover cohort<br>Subjects from the original phase 1 study of peanut SLIT (NCT00429429) who were rolled over into the current protocol as an open label peanut SLIT cohort. | Drug: Peanut SLIT<br>* Liquid peanut protein drops diluted in glycerin which are dosed under the tongue.<br>* Other names: Sublingual peanut protein drops;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Can Tolerate the Peanut Oral Food Challenge After 12 Months of Peanut SLIT Dosing | Upon completion of 12 months of peanut SLIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCFC) to assess desensitization (an increase in reaction threshold while on therapy). A DBPCFC involves the ingestion of small increasing amounts of peanut up to a cumulative total amount. The primary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 2500 mg peanut protein DBPCFC without developing symptoms after 12 months of peanut SLIT therapy. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Tolerating a Peanut Oral Food Challenge 2-4 Weeks After Discontining Peanut SLIT Dosing | Upon completion of 36-60 months of peanut SLIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCFC) to assess desensitization (an increase in reaction threshold while on therapy). A DBPCFC involves the ingestion of small increasing amounts of peanut up to a cumulative total amount. Peanut SLIT therapy was then discontinued for 2-4 weeks to assess for persistence of the desensitization response called sustained unresponsiveness (SU). The secondary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5000 mg peanut protein DBPCFC without developing symptoms 2-4 weeks after discontinuing peanut SLIT therapy. | 36-60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peanut Allergy, Sublingual immunotherapy