Oral Immunotherapy (OIT) for Peanut Allergy

Study Overview
=================
Brief Summary
-----------------
Peanut allergy is known to cause severe anaphylactic reactions.The goal of this proposal is to produce a new treatment that would benefit subjects who have peanut allergy by lowering the risk of anaphylactic reactions (desensitization), and changing the peanut-specific immune response in subjects who have peanut allergy (tolerance).

Detailed Description
-----------------
Peanut allergy is known to cause severe anaphylactic reactions. Compared with other food allergies it tends to be more persistent and also its prevalence seems to be rising. Currently there is no proven treatment other than strict avoidance. We are attempting to decrease the risk of anaphylaxis on accidental ingestion by desensitizing subjects to peanut using peanut oral immunotherapy (OIT). We are also studying the effect of peanut OIT on the peanut specific immune response to determine if tolerance to peanut protein will develop. Children ages one to six years of age with peanut allergy will be randomized to peanut OIT or placebo (active subjects). Thirty subjects will also be recruited as controls. These subjects will not receive any peanut or placebo but only have skin prick testing and lab work in addition to a history and physical exam. Active subjects will undergo a modified rush immunotherapy on the first day and then increase the doses at least every two weeks up to a maintenance dose of 4 grams (equivalent to about 13 peanuts). Doses will be taken daily at home except for dose increases which will be done on the research unit. Outcome variables of interest include response to double-blind placebo controlled food challenge, skin prick testing, peanut specific IgE, and adverse events. These results will be compared between the start and end of peanut OIT using appropriate statistical analysis.

Official Title
-----------------
Oral Immunotherapy for Peanut Allergy- Peanut Oral Immunotherapy (PnOIT3)

Conditions
-----------------
Peanut Hypersensitivity

Intervention / Treatment
-----------------
* Drug: Peanut OIT
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 1- 6 years all of either sex, any race, any ethnicity at the time of the initial visit The presence of IgE specific to peanuts (a positive skin prick test to peanuts (diameter of wheal >3.0 mm) and a positive in vitro IgE [CAP-FEIA] > 7 kUA/L A history of significant clinical symptoms occurring within 60 minutes after ingesting peanuts Provide signed informed consent Exclusion Criteria: History of severe anaphylaxis to peanut as defined by hypoxia, hypotension, or neurological compromise (Cyanosis or oxygen saturation < 92% at any stage, hypotension, confusion, collapse, loss of consciousness; or incontinence) Currently participating in a study using an investigational new drug Participation in any interventional study for the treatment of food allergy in the past 12 months Subjects with a known wheat food allergy will be excluded because of cross contamination of oat with wheat Poor control or persistent activation of atopic dermatitis Moderate to severe persistent asthma Currently being treated with greater than medium daily doses of inhaled corticosteroids, as defined by the National Heart Lung and Blood Institute (NHLBI) guidelines Inability to discontinue antihistamines for skin testing and oral food challenges (OFCs)

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Peanut OIT<br>Subjects randomized to receive active treatment with peanut protein flour. | Drug: Peanut OIT<br>* Peanut flour that is orally ingested in a graded fashion.<br>* Other names: Peanut flour;|
| Placebo Comparator: Placebo<br>Subjects randomized to receive placebo in the form of oat flour. | Drug: Placebo<br>* Oat flour used as a placebo that is orally ingested a graded fashion<br>* Other names: Oat flour;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Tolerance as Defined by a Negative DBPCFC 4 Weeks After Discontinuation of Peanut OIT Therapy. | Upon completion of 60 months of peanut OIT treatment, subjects discontinued peanut OIT for 4 weeks. The primary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5 gm peanut protein double-blind placebo controlled food challenge (DBPCPFC) without developing symptoms 4 weeks after discontinuing peanut OIT. | 61 months for those randomized to active treatment and 73 months for those randomized to placebo for the initial 12 months of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Achieving Full Desensitization as Defined by a Negative DBPCFC After 60 Months of Peanut OIT Therapy. | Upon completion of 60 months of peanut OIT treatment, subjects underwent a double-blind placebo controlled food challenge (DBPCPFC) to assess desensitization. The secondary clinical efficacy outcome of the study was the percentage of peanut allergic subjects who completed a 5 gm peanut protein double-blind placebo controlled food challenge (DBPCPFC) without developing symptoms after completing peanut OIT therapy. | 60 months for those randomized to active treatment and 72 months for those randomized to placebo for the initial 12 months of therapy | 
| The Percentage of Subjects Who Tolerated the Initial-day Escalation to 6 mg of Peanut | The first day of peanut OIT dosing involved multiple increasing doses of peanut flour in what was called an initial escalation day up to a maximum dose of 6 mg of peanut protein. The secondary outcome measure assessed the percentage of subjects were successfully able to reach this 6 mg dose. | first day of peanut OIT dosing | 
| The Percentage of Subjects Who Are Successfully Able to Escalate up to the 4000 mg Maximum Maintenance Dose of Peanut Protein OIT During the 60 Month Desensitization Phase of the Study | During the desensitization phase of the study, subjects under go an initial day escalation up to a maximum of 6 mg of peanut protein. They then undergo biweekly dose escalation over approximately 10 months up to a maximum dose of 4000 mg of peanut protein. This outcome reports the percentage of subjects that achieve this. | approximately 40 weeks (10 months) | 
| Incidence of All Serious Adverse Events During the Study | All serious adverse events during the blinded and open-label phases of the study were recorded and reported as a safety outcome. | 61 months for those randomized to active peanut OIT and 73 months for those randomized to placebo for the initial 12 months of the study. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peanut Allergy