A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Sublingual/Oral Immunotherapy for the Treatment of Peanut Allergy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to explore the safety and efficacy of a sublingual (under the tongue) immunotherapy (SLIT) dosing regimen and an oral immunotherapy (OIT) regimen in inducing desensitization and long term tolerance in children with persistent peanut allergy.

Detailed Description
-----------------
To effectively address the Primary Objectives of this pilot study, 30 subjects aged 6-21 years with: (1) a convincing clinical history of peanut allergy (PA), (2) a serum immunoglobulin E (IgE) specific to peanut of >0.35 kilo units per liter (kU/L) and a skin prick test (SPT) wheal >3 mm, will be enrolled. Subjects will be recruited from the Johns Hopkins Pediatric Allergy Clinic. Participants will undergo an initial screening visit that will include a medical history, physical exam, skin testing, and phlebotomy. Informed consent and assent will be obtained. At the next two visits, 20 participants will complete a double-blind placebo-controlled food challenge (DBPCFC). Eligible subjects will be randomized in a 1:1 ratio into two groups. One group will receive active SLIT with placebo OIT and the other group will begin active OIT with placebo SLIT dose escalation. Over the next 16 weeks of the study, subjects will undergo SLIT and OIT dose increases. A maintenance dose will then be taken at home daily for 12 months. A DBPCFC will be completed after 6 months and 12 months of home dosing. Those patients who pass the DBPCFC will be taken off SLIT and OIT for 4 weeks. A final challenge will be administered at the end of this period. Ten additional peanut-allergic subjects age 6-21 years will be enrolled and followed as longitudinal controls for the mechanistic studies. These subjects will follow a modified schedule compared to those subjects receiving study treatment and will be evaluated by phlebotomy, end point titration prick skin testing, and saliva collection. These patients will continue strict avoidance of peanut unless otherwise advised by their personal physician.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Sublingual/Oral Immunotherapy for the Treatment of Peanut Allergy

Conditions
-----------------
Peanut Hypersensitivity, Food Hypersensitivity, Immediate Hypersensitivity

Intervention / Treatment
-----------------
* Drug: Peanut powder
* Drug: Peanut extract
* Drug: Placebo extract
* Drug: Placebo powder


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Are ages 6 to 21 years of either sex, any race, and any ethnicity at the time of the initial visit. Have a physician diagnosed peanut allergy or a convincing clinical history of peanut allergy (urticaria, upper or lower respiratory symptoms, GI disturbances, rash or oral symptoms). Have a skin prick test positive to peanut (diameter of wheal 3 mm ≥ negative control) and detectable serum peanut-specific IgE level (UniCAP ≥ 0.35 kU/L). Have a positive reaction to a cumulative dose of ≤1,000 mg of peanut powder in the initial qualifying DBPCFC. Use an effective method of contraception by females of childbearing potential to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of their participation in the study. Ability to perform spirometry maneuvers in accordance with the American Thoracic Society (ATS) guidelines (1994). Have self-injectable epinephrine (i.e. EpiPen® or EpiPen Jr.®) available at all times. Provide signed informed consent (by parent or legal guardian if the subject is a minor) and informed assent if applicable. Exclusion Criteria: Have a history of severe anaphylaxis to peanut with hypoxia (cyanosis or peripheral capillary oxygen saturation (SpO2) ≤92% at any stage), hypotension or neurological compromise (confusion, collapse, loss of consciousness or incontinence). Tolerates more than 1,000 mg of peanut powder at the initial qualifying DBPCFC. Have a viral upper respiratory infection (URI) or gastroenteritis within 7 days of OFC (OFC will need to be rescheduled). 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. Pregnancy or lactation Allergy to placebo ingredients (Glycerin or oat flour) OR reacts to any dose of placebo during the qualifying OFC. Currently in a buildup phase of any allergy immunotherapy. Poor control of atopic dermatitis. Have pulmonary function tests with forced expiratory volume 1 (FEV1) value <80% predicted or any clinical features of greater than moderate persistent asthma and greater than high daily doses of inhaled corticosteroids (>500µg/day fluticasone or equivalent). Use of steroid medications (oral steroids, such as prednisone or Medrol, steroid injections, such as Kenalog, or IV or oral corticosteroid burst) in the following manners: o History of daily oral steroid dosing within 4 weeks prior to baseline visit or for > 1 month during the past year or burst oral steroid course in the past 6 months or > 1 burst oral steroid course in the past year. Asthma requiring ≥1 hospitalization in the past year for asthma or >1 ER visit in the past 6 months for asthma Use of omalizumab or other non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immuno-modulatory therapy (not including corticosteroids) or biologic therapy within the past year. Use of β-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB), calcium channel blockers or tricyclic antidepressant therapy. Inability to discontinue antihistamines for 5 days for long acting and 3 days for short acting prior to skin testing or OFC's. History of alcohol or drug abuse. Active eosinophilic gastrointestinal disease in the past two years. Have other significant medical conditions (e.g., liver, gastrointestinal, kidney, cardiovascular, pulmonary disease, or blood disorders) which, in the opinion of the Investigator, make the subject unsuitable for induction of food reactions. Any previous intubation due to allergies or asthma. Severe reaction at initial DBPCFC, defined as: Life-threatening anaphylaxis Requiring overnight hospitalization

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 21 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active SLIT/Placebo OIT<br>These subjects will receive peanut powder given orally and placebo extract given sublingually. | Drug: Peanut powder<br>* Delivered orally<br>Drug: Placebo extract<br>* Delivered sublingually<br>|
| Experimental: Active OIT/Placebo SLIT<br>These subjects will receive peanut extract given sublingually and placebo powder given orally. | Drug: Peanut extract<br>* Delivered sublingually<br>Drug: Placebo powder<br>* Delivered orally<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Induced Peanut Desensitization at 12 Months | Peanut desensitization was defined as a greater than 10-fold increase in oral food challenge (OFC) threshold after 12 months of therapy. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between Arm Change in IgG4 From Baseline to End of Dose Build-up (up to 16 Weeks) | Serum immunoglobulin G4 (IgG4) levels are measured in milligrams of Antibody per liter (mga/L) and were collected at baseline and at the end of dose build-up (up to 16 weeks) | Baseline and end of dose build-up (up to 16 weeks) | 
| Between Arm Change in IgG4 From Baseline to 6 Months | IgG4 levels are measured in milligrams of Antibody per liter (mga/L) and were collected at baseline and at 6 months | Baseline and 6 months | 
| Between Arm Change in IgG4 From Baseline to 12 Months | IgG4 levels are measured in milligrams of Antibody per liter (mga/L) and were collected at baseline and at 12 months | Baseline and 12 months | 
| Between Arm Change in IgE From Baseline to End of Dose Build-up (up to 16 Weeks) |  | Baseline to end of dose build-up (up to 16 weeks) | 
| Between Arm Change in IgE From Baseline to 6 Months | Serum immunoglobulin E (IgE) levels are measured in kilo units of Antibody per liter (kUa/L) and were collected at baseline and at 6 months | Baseline and 6 months | 
| Between Arm Change in IgE From Baseline to 12 Months | IgE levels are measured in kilo units of Antibody per liter (kUa/L) and were collected at baseline and at 12 months | Baseline and 12 months | 

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