Nasal Allergen Challenge Test as a Method to Detect Clinical Reactivity Against Birch Pollen

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.