Clinical trial NCT05297760: Intralymphatic Immunotherapy With Polvac Grass & Rye Allergen Extract
Official title: Documentation of Efficacy for Intralymphatic Allergen Immunotherapy in a Phase III Randomized, Parallel Group, Double Blind Placebo-controlled Multisite Field Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rhinitis, Allergic, Seasonal
Rhinitis; Allergic, With Asthma
Allergic Rhinitis
Allergic Rhinitis Due to Grass Pollen
Allergic Asthma
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: University of Aarhus
First posted: 2022-03-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Addition on January 12th 2024:

After unblinding of the study in October to December 2023 and after analysis of the primary endpoint, it was decided to prolong the study in a semi-cross over. That means, study participants that received placebo in the original trial (n=30) will receive active treatment in an open label setting. The treatment will be exact similar to that of the active treatment in 2022, i.e., three ILIT injections of the IMD (Polvac Grass+Rye) with 4 weeks intervals and using the same dose as in 2022. The study participants that originally received active treatment (n=30) will not receive further treatment.

All patients (n=60), will be invited to enter symptoms and medication usage during the pollen season of 2024, similar to 2022 and 2023. In September to November 2024, the all patients will be invited for a final follow-up visit for clinical and laboratory tests. All patients will concent to the trial extension in writing prior to entering the trial extension.

Eligibility criteria: 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.

Primary outcomes:
measure: Combined symptom medication score (cSMS)
timeFrame: 3 months (2 minutes per day)
Secondary outcomes:
measure: Rhino conjunctivitis quality of life score (RQLQ)
timeFrame: 3 months (10 minutes per week)
measure: Lower airway disease
timeFrame: 10 minutes (5 times in two years)
measure: Asthma
timeFrame: 10 minutes (5 times in two years)
measure: Biomarkers
timeFrame: 5 minutes (8 times in two years)
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: Univeristät Zürich, Dermatologische Klinik
name: Pål Johansen, PhD
role: PRINCIPAL_INVESTIGATOR
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