Promoting Tolerance to Common Allergens in High-Risk Children: Global Prevention of Asthma in Children (GPAC) Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether early childhood exposure to common allergens (substances that can trigger allergies and asthma) can prevent the development of asthma in children at high risk for developing the disease.

Detailed Description
-----------------
Researchers suspect that allergies to common inhaled allergens (such as house dust mite, cat dander, and grass pollens) are a major cause of childhood asthma. Recent evidence suggests that if allergies to inhaled allergens are prevented, this can cause changes in the immune system that may inhibit the development of asthma. Although strategies to prevent allergies generally focus on avoiding the allergen, complete avoidance of the common allergens linked to asthma would require extreme measures and is impractical. Oral mucosal immunoprophylaxis (OMIP) therapy is an allergy treatment that can induce long-lasting immune tolerance in people already suffering from allergies. By exposing the patient to small, repeated, but increasing doses of the problem allergen over a long period of time, the patient's immune system is eventually desensitized to that particular allergen. OMIP therapy has been shown to be safe in children as young as 2 years old. This study will evaluate if OMIP therapy against common inhaled allergens is safe and effective in preventing the development of asthma in children at high risk for developing the disease. Children enrolled in this study have been diagnosed with eczema or food allergies and have a family history of eczema, allergic rhinitis, or asthma. There are two groups in this study. The experimental arm participants will receive OMIP therapy (a mixture of house dust mite, cat, and timothy grass allergens) as daily oral drops under the tongue for 1 year; Placebo arm participants will receive an allergen free placebo solution. Participants will be followed for an additional 3 years to see whether they develop allergies or asthma and to determine how OMIP affects their immune system's response to allergens. There will be 5 study visits in the first year and 6 visits over the next 3 years. At all visits, participants will be assessed for allergy/asthma symptoms, will be asked to complete questionnaires, and may be asked to provide blood or saliva samples.

Official Title
-----------------
A Phase II Multicenter, Controlled, Double-Blind Study Using Immunoprophylaxis in the Primary Prevention of Allergic Disease (ITN025AD)

Conditions
-----------------
Asthma, Allergic Sensitization

Intervention / Treatment
-----------------
* Biological: Oral mucosal immunoprophylaxis (OMIP)
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with eczema (atopic dermatitis) Family history of eczema, allergic rhinitis, or asthma Allergy to one or more of the following: egg white, cow's milk, peanut, or soybean Weigh at least 9.5 kg (20.9 lbs) Parent or guardian willing to provide informed consent Exclusion Criteria: Allergy to house dust mite, cat, or timothy grass Born prematurely (before 36th week's gestation) Previous diagnosis of asthma OR have had 3 or more distinct episodes of wheeze during the first year of life Chronic pulmonary disease Chronic disease requiring therapy Past or current treatment with systemic immunomodulator medication Past or current treatment with allergen-specific immunotherapy Received 10 or more days of systemic steroids in the 3 months prior to study entry Orofacial abnormalities that are likely to interfere with the subject's ability to take study treatment Participated in another clinical study within the 3 months prior to study entry

Ages Eligible for Study
-----------------
Minimum Age: 12 Months
Maximum Age: 30 Months

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

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

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral mucosal immunoprophylaxis (OMIP)<br>Participants are administered oral mucosal immunoprophylaxis (OMIP) daily for 12 months. | Biological: Oral mucosal immunoprophylaxis (OMIP)<br>* OMIP consists of a mixture of allergen extracts including 0.2 milliliters (mL) timothy grass, 0.2 mL cat, and 0.2 mL house dust mite for a total daily dose of 0.6 mL.<br>* Other names: Allergen immunotherapy;|
| Placebo Comparator: Placebo<br>Participants are administered, via the same route as the experimental group, an oral placebo solution daily for 12 months. | Biological: Placebo<br>* The placebo consists of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Allergic Sensitization at Month 36 Status Post Treatment Completion | Allergic sensitization is defined as a positive serum allergen specific Immunoglobulin E (IgE) CAP test[1] or a positive allergy skin prick test[2]. Not experiencing allergic sensitization is the better outcome for this measure. A positive serum allergen specific IgE CAP (ImmunoCAP) test result is defined by a result >= 0.35 kU/L. Higher scores indicate greater allergic sensitization. A positive skin prick test is defined as a wheal diameter that is 3 mm larger than that produced by a negative control. Higher wheal sizes indicate greater allergic reaction or sensitization. | Three years (36 months) after Treatment Completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Current Asthma at Month 36 Status Post Treatment Completion | Participants who currently have asthma three years after end of treatment. Asthma is defined as three distinct episodes of wheeze after the first year of life, each of which lasts 3 or more consecutive days and occurs in a clinical setting where asthma is likely and other likely conditions have been excluded. Episodes must be separated by at least 7 days without wheeze. Current asthma is defined as a diagnosis of asthma and at least one episode of wheeze lasting 3 or more consecutive days in the past 12 months. | Three years (36 months) after Treatment Completion | 
| Time to First Onset of Asthma | Time to first onset of asthma is the time from the day a participant is randomized and initiates study treatment to the diagnosis of the first of three episodes of asthma. Asthma is defined as three distinct episodes of wheeze after the first year of life, each of which lasts 3 or more consecutive days and occurs in a clinical setting where asthma is likely and other likely conditions have been excluded. Episodes must be separated by at least 7 days without wheeze. | From Treatment Initiation to Month 36 Status Post Treatment Completion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
asthma, allergen, allergic disease, allergen immunotherapy, allergic sensitization, atopic dermatitis, eczema, food allergy, oral mucosal immunoprophylaxis (OMIP)