Intralymphatic Immunotherapy With Polvac Grass & Rye Allergen Extract

Study Overview
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Brief Summary
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The primary goal is to investigate the efficacy of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis and allergic asthma due to sensitisation to grass pollen allergens. 60 patients with allergic rhinitis will be included and randomized to receive either Polvac (n=30) or placebo (n=30). All patients will receive three injections with 4-8 weeks interval. The injections into a inguinal lymph node is guided by sonography. Patients will record symptoms and medication use in the summer of 2022 and 2023.

Detailed Description
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This study is part of a multicenter trial Phase III that takes place also in Denmark and Sweden (EudraCT registration number 2020-001060-28). The primary goal is to investigate the efficacy of intralymphatic immunotherapy (ILIT) for the treatment of allergic rhinitis and allergic asthma due to sensitisation to grass pollen allergens. In the Swiss arm of trial, Polvac (Allergy Therapeutics, United Kingdom) is applied. In Denmark and Sweden, the applied drug is Alutard (ALK, Denmark). The major difference is the excipient adjuvant, which is microcrystallin tyrosine (MCT) in Polvac aluminium in Alutard. The concentration of major allergen 60 phl p5, as the active ingredient, is the same in both products. The active ingredient is a standardised grass pollen allergen extract combined with MCT. The allergen extract has been treated with glutaraldehyd as to reduce allergenicity, i.e., increase the safety. In Switzerland and Germany, Bencard AG is providing the product. Polvac™, is a marketed product that is approved by the Swiss Medical Product Agencies and adheres to GMP. The product consists of needle-like crystalline structures of average 20 micrometer size. Polvac is approved for subcutaneous immunotherapy (SCIT), which consists of 6 pre-seasonal injections with 1-2 week intervals for 3-4 years, adding up to a total of 18 to 24 injections for the treatment to be completed. In the currents study, 60 patients with allergic rhinitis will be included and randomized to receive either Polvac (n=30) or placebo (n=30). Primary screening is done online through questionnaires. Secondary screening and inclusion is done clinical at the University Hospital Zurich. All patients will receive three injections of Polvac or placebo (saline) with 4-8 weeks interval. The injections into a inguinal lymph node is guided by sonography. For three days post each injections, adverse events will be recorded by patients using an on line application. In the summer seasons of 2022 and of 2023, the patients will record daily allergic symptoms and daily medication usage using an online application. These record are the basics for the efficacy analysis.

Official Title
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Documentation of Efficacy for Intralymphatic Allergen Immunotherapy in a Phase III Randomized, Parallel Group, Double Blind Placebo-controlled Multisite Field Trial

Conditions
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Rhinitis, Allergic, Seasonal, Rhinitis; Allergic, With Asthma, Allergic Rhinitis, Allergic Rhinitis Due to Grass Pollen, Allergic Asthma

Intervention / Treatment
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* Biological: Polvac Grass+Rye
* Drug: Saline 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: passed online screening with a Rhinoconjunctivitis Total Symptom Score (RTSS) value of 8 or higher. sensitisation to grass pollen allergens with a skin prick test reaction to grass pollen allergen of 3 mm or more. eligible to allergen immunotherapy. 18 years or older. comfortable with digital data entry. Exclusion Criteria: previous grass pollen-specific immunotherapy. significant allergy to mugwort or pet animal allergens. uncontrolled asthma. upper airway disease. severe pulmonary disease. recent allergic reactions. immunosuppression. cardiovascular disease. malignant disease. use of ACE-blockers. other diseases or conditions rendering the treatment of anaphylactic reactions difficult.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Polvac<br>Polvac Grass+Rye | Biological: Polvac Grass+Rye<br>* Suspension of micro crystalline tyrosine with grass and rye pollen allergen<br>|
| Placebo Comparator: Placebo<br>Saline | Biological: Polvac Grass+Rye<br>* Suspension of micro crystalline tyrosine with grass and rye pollen allergen<br>Drug: Saline 0.9%<br>* Physiological saline solution for use as vehicle for the biological drug (Polvac Grass+Rye) or as placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined symptom medication score (cSMS) | Daily registration of symptoms and medication usage by the study participants and by means of a online application. This is done during the pollen season of 2022 (and possible 2023 if the 2022 season is poor with low amounts of pollen). The assessment is done over a time period, but the records are integrated for the calculation of one single score (cSMS), which is the primary outcome. | 3 months (2 minutes per day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rhino conjunctivitis quality of life score (RQLQ) | Weekly questionnaire for studying the quality of life of the study participants during the pollen season of 2022 (and possible 2023 if the 2022 season is poor with low amounts of pollen). The RQLQ will assess seven domains on a weekly basis on a scale from 0 (best) to 6 (worst). The assessment is done over a long time period, but the records are integrated for the calculation of one single score (RQLC), which is the secondary outcome. | 3 months (10 minutes per week) | 
| Lower airway disease | We will assess spirometry, at each follow-up time point (winter and summer visits) and analyse a time series of the development of each parameter in each treatment group. The assessments will be performed at several time-points and the changes from baseline assessments (before ILIT) is measured. | 10 minutes (5 times in two years) | 
| Asthma | We will assess FeNo (Fraction Exspiratory Nitric Oxide) at each follow-up time point (winter and summer visits) and analyse a time series of the development of each parameter in each treatment group. The assessments will be performed at several time-points and the changes from baseline assessments (before ILIT) are measured. | 10 minutes (5 times in two years) | 
| Biomarkers | Circulating levels of IgE, IgG1, and IgG4 specific for grass pollen extract and the major allergens Phl p 5 and Phl p 1 will be determined in blood samples before every treatment and at all the follow-up visits, for a total of 7 times per participant. The analysis is done using ImmunoCAP ELISA. In addition, IgE assessment by ISAC (112 allergens in one array) will be performed to analyse if sensitisation to other allergens develops or changes. All assessments will be performed at several time-points and the changes from baseline assessments (before ILIT) are measured. | 5 minutes (8 times in two years) |