Immunological Mechanisms of Oralair® in Patients With Seasonal Allergic Rhinitis

Study Overview
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Brief Summary
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Allergic diseases represent a major health issue worldwide and epidemiological studies in Melbourne, Australia, have reported a high prevalence of rhinitis (hayfever) and atopy (genetic tendency to make allergy antibody) in Asian and Caucasian subjects. Mainstay treatment of allergic rhinitis is allergen avoidance and pharmacotherapy for symptom relief. Allergen immunotherapy offers the advantages of specific treatment with long lasting efficacy, and can modify the course of disease. However, use of this treatment is restricted by the high risk of adverse events especially in asthmatics. Other, better tolerated, routes of allergen administration than the current conventional subcutaneous route (SCIT) have been investigated including the sublingual route (SLIT) and recently sublingual tablets for pollen allergy immunotherapy became available. The tablets are safe and easy to use and contain pollen extracts from 5 of the most common allergy-causing European grasses but include ryegrass (Lolium perenne), the major seasonal pollen for allergy in Melbourne and south-eastern Australia. The immunological mechanisms of sublingual immunotherapy are not fully understood. The investigators propose conducting a longitudinal open label study to investigate the immunological changes that occur with the 5 grass pollen sublingual immunotherapy tablet (Oralair®) in a cohort of Chinese and non-Chinese background subjects. The investigators will investigate the induction of relevant T cell regulatory immune mechanisms and changes in serum allergen-specific immunoglobulin (Ig) E and IgG4. Immunoregulatory cytokine synthesis and T cell phenotype (Bio-plex and flow cytometry) will be examined. This project will provide important fundamental knowledge on which to inform decisions for the greater application of this treatment for subjects with moderate and severe allergic rhinitis.

Official Title
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Immunological Mechanisms of Oralair® (5 Grass Mix Sublingual Allergen Immunotherapy Tablet) in Patients With Seasonal Allergic Rhinitis

Conditions
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Allergic Rhinitis

Intervention / Treatment
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* Other: Grass pollen sublingual immunotherapy tablet
* Drug: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects of Chinese heritage or non-Chinese heritage Clinical diagnosis of moderate to severe seasonal allergic rhinitis Ryegrass-specific IgE : CAP-Pharmacia score > 1 Exclusion Criteria: Ongoing immunotherapy or previous immunotherapy (within last 5 years) Continuous oral corticosteroids Moderate, severe or unstable asthma Standard contraindications for allergen immunotherapy Ongoing treatment with β-blockers Immunodeficiency diseases Malignancy Significant inflammatory condition or disease in the oral cavity

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Grass pollen sublingual immunotherapy tablet<br>A sublingual allergen immunotherapy tablet (Oralair) containing: 300 index of reactivity (IR) of 5 grass pollen allergen extracts:perennial ryegrass (Lolium perenne), meadow grass (Poa pratensis), timothy grass (Phleum pratense), cocksfoot (Dactylis glomerata) and sweet vernal grass (Anthoxanthum odoratum) in an open label fashion administered for 4 months prior to the pollen season. | Other: Grass pollen sublingual immunotherapy tablet<br> <br> |
| Other: Control<br>Standard medical therapy: oral antihistamines AND/OR nasal steroids AND/OR nasal antihistamines | Drug: Control<br> <br> * Other names: Oral anthistamines AND/OR Nasal steroids AND/OR Nasal antihistamines;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Ryegrass specific-IgG4 at 4 months and 12 months |  | Baseline, 4 months, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life assessed by an Allergic Rhinitis Quality of Life Questionnaire at 4, 8 and 12 months |  | Baseline, 4 months, 8 months, 12 months | 
| Change in Combined Symptoms and Medication requirements score at 4, 8 and 12 months |  | Baseline, 4 months, 8 months, 12 months | 
| Change in Fractional Exhaled Nitric Oxide at 4, 8, and 12 months |  | Baseline, 4 months, 8 months, 12 months | 
| Change in Helper and regulatory T cell response to ryegrass pollen at 4 months and 12 months |  | Baseline,4 months, 12 months | 
| Change in Ryegrass-specific IgE at 4 months and 12 months |  | Baseline, 4 months, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgE, Allergic rhinitis, Asthma, Regulatory T cells, IgG4