Clinical efficacy and tolerability for allergen specific immunotherapy (AIT) with Itulazax (birch pollen extract tablet) is well established. Allergen challenges are used by clinicians to confirm correct diagnosis and by researchers to evaluate the efficacy of different interventions, eg. AIT. The challenge is performed by using a specific controlled administration schedule of an allergen product in the shock organ (nose, eye, or airway) and then monitor the result. Nasal Allergen Challenge (NAC) is the most common allergen challenge used. Aquagen SQ (birch pollen extract) has since decades been golden standard for this purpose, but production of this product ended 2019. Clinicians as well as researchers are now in need for an alternative product. To evaluate a new method for NAC would be of value from a clinical- and research perspective. From a Nordic perspective a NAC study with dissolved Itulazax would be of special interest since birch allergy is a dominant allergen in the region. In a recently published article it was shown that dissolved Grazax and Aquagen Phleum pratense gave comparable result used in grass allergic patients. Therefore, it seems reasonable to assume that the same method could be used with dissolved Itulazax. The aim of this clinical trial is to evaluate the feasibility of nasal allergen challenge tests with dissolved Itulazax tablets. The main benefit of this proposal is that the allergen composition of the provocation test product is the same as the final product to be treated with. This is likely to increase the treatment motivation of the patient. In addition, the dissolving process is easier for the physician compared to the dissolving of the previously used Aquagen.
The objective of the trial is to establish a method for Nasal Allergen Challenge (NAC) with dissolved Itulazax. This trial is an open-label, national, one-centre trial comparing the results of NAC applied by solutions of dilutions of dissolved Itulazax tablets with the clinical diagnosis of birch pollen allergy by an experienced physician. To ensure negative reactivity to the excipients of the tablet and the nasal provocation itself a non-atopic control group of 20 subjects will be challenged with both a dissolved placebo-tablet and 0.9% saline solution. This provocation will be performed as a one-sided blinded challenge which will demonstrate that the NAC is truly negative. Thereafter 70 patients will initially receive a NAC with 0,9% saline solution to ensure negative reactivity to the challenge as method. If negative after 30 minutes NAC will continue with one puff (1x0.1 ml) dissolved Itulazax (1 SQ-Bet/ml) in each nostril. Total nasal symptom scores (TNSS, 0-12) and peak nasal inspiratory flow (PNIF) will be recorded before NAC and then at 5, 15 and 30 minutes.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
SINGLE
Enrollment
89
Active ingredients: Birch (Betula verrucosa) extracts Dosage form: Oral lyophilisate (referred to as allergy immunotherapy tablet in text) Dose/strength: 12 SQ-Bet Excipients: Gelatine (fish source), mannitol and sodium hydroxide
Active ingredients: None Dosage form: Oral lyophilisate (referred to as allergy immunotherapy tablet in text) Excipients: Gelatine (fish source), mannitol and sodium hydroxide
Sodium chloride solution 9mg/ml
Karolinska University Hospital
Stockholm, Sweden
TNSS
0,1 x ml of dissolved Itulazax or NaCl will be sprayed into each nostril. The change from baseline (TNSS before provocation) in Total Nasal Symptom Score (TNSS) will be measured 5,15 and 30 minutes after negative (NaCl) and positive provocation (Itulazax). Subjective measures will be made by a Total Nasal Symptom Score (TNSS) on a 0-12 Likert scale. Increase of ≥5 points indicates clearly positive test. Increase of ≥3 points indicates moderately positive test
Time frame: The symptoms are scored 5,15 and 30 minutes after provocation
PNIF
0,1 x ml of dissolved Itulazax or NaCl will be sprayed into each nostril. Peak nasal inspiratory flow (PNIF) wil be meaused with a PNIF Meter. The change from baseline (PNIF before provocation) in Peak Nasal Inspiratory Flow (PNIF) will be measured 5,15 and 30 minutes after negative (NaCl) and positive provocation (Itulazax). Objective measures will be an assessment of the Peak Nasal Inspiratory Flow (PNIF). Flow decrease of ≥40% indicates clearly positive test. Flow decrease of ≥20% indicates moderately positive test.
Time frame: The symptoms are scored 5,15 and 30 minutes after provocation.
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