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

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

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

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.

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.

asthma, allergen, allergic disease, allergen immunotherapy, allergic sensitization, atopic dermatitis, eczema, food allergy, oral mucosal immunoprophylaxis (OMIP)

Participants are administered, via the same route as the experimental group, an oral placebo solution daily for 12 months.

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.

The placebo consists of three 0.2 mL vials of solution mixed together for a total daily dose of 0.6 mL.

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.

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.

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.

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

Data access is provided to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.

Mascarell L, Van Overtvelt L, Moingeon P. Novel ways for immune intervention in immunotherapy: mucosal allergy vaccines. Immunol Allergy Clin North Am. 2006 May;26(2):283-306, vii-viii. doi: 10.1016/j.iac.2006.02.009.

Nelson HS. Advances in upper airway diseases and allergen immunotherapy. J Allergy Clin Immunol. 2006 May;117(5):1047-53. doi: 10.1016/j.jaci.2005.12.1306. Epub 2006 Mar 6.

Holt PG, Sly PD, Sampson HA, Robinson P, Loh R, Lowenstein H, Calatroni A, Sayre P. Prophylactic use of sublingual allergen immunotherapy in high-risk children: a pilot study. J Allergy Clin Immunol. 2013 Oct;132(4):991-3.e1. doi: 10.1016/j.jaci.2013.04.049. Epub 2013 Jun 12. No abstract available.

Study summary, -design with synopsis, -adverse events, -assessment, -medications, -demographics, -lab tests, -files, et al.

Study overview with synopsis, -navigator, -schedule of events, -data and reports, biospecimens and availability.