D2.190 - Evaluation of a commercially available Birch Pollen Extract for its suitability in Nasal Allergen Challenges: Feasibility and Dose-Response Assessment

Allergic rhinoconjunctivitis is characterized by nasal and ocular symptoms such as sneezing, rhinorrhea, tearing, and pruritus following exposure to environmental allergens. Controlled provocation using Nasal Allergen Challenge (NAC) is a validated method for assessing allergic responses and investigational product efficacy. This exploratory study aimed to evaluate the ability of a commercially available birch pollen extract to elicit reproducible allergic responses in sensitized individuals and to optimize allergen dosing for future trials.

Eligible healthy adults with a history of seasonal birch allergy along with a positive birch skin prick test and Bet v 1-specific IgE ≥ 0.7 kAU/L (ImmunoCAP®) were studied under an IRB approved protocol. NAC was performed using incremental doses of birch pollen extract. Responses were assessed by Total Nasal Symptom Score (TNSS) and Peak Nasal Inspiratory Flow (PNIF). Qualifying criteria included TNSS ≥ 6 and PNIF reduction ≥ 30% compared to control (diluent without allergen) NAC. The study was conducted in two parts: Part 1 utilized lower-concentration allergen solutions, while Part 2 employed higher-concentration allergen dose steps to streamline preparation and reduce unnecessary allergen exposures. 

Of 13 screened subjects, 12 completed allergen NAC (6 subjects per part). All demonstrated positive responses at one or more dose levels. In Part 1, qualifying responses were first observed at 75 ng/200 µL (33%) and 874 ng/200 µL (67%). In Part 2, qualifying responses occurred at 97 ng/200 µL (50%) and 1949 ng/200 µL (100%). These subjects also underwent up-dosing to 4871 ng/200 µL beyond the qualifying dose to characterize the dose-response. TOSS scores varied (0–3 in Part 1; 0–8 in Part 2) without consistent trends.  There were no unexpected safety issues reported throughout the study.

A commercially available (in North America) birch pollen extract reliably and safely induced measurable allergic responses and a dose response in sensitized participants, confirming its suitability for NAC challenges. Higher-concentration dose steps improved operational efficiency and consistency. These findings support the feasibility of NAC with this birch pollen extract and provide critical dose-response data for designing future clinical trials or for use in the clinical practice.