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

Inclusion Criteria:

• Written informed consent obtained before any trial related assessments are performed

• Male or female aged 18-65 years at the time of consent

• A female subject of child-bearing potential must have a negative pregnancy test andbe willing to practise appropriate highly effective birth control methods. Thedefinition of a female patient of childbearing potential is a nonmenopausal femalewho has not had a hysterectomy, bilateral oophorectomy, or medically documentedovarian failure.

• The subject must be willing and able to comply with the trial protocol

• Birch pollen allergy group: A documented clinically relevant history of moderate tosevere persistent birch pollen allergy symptoms since at least 2 years withtroublesome symptoms despite the use of symptomatic medication with or withoutasthma; positive SPT(skin prick testing) response (wheal diameter ≥3 mm) to birchpollen (birch) and positive specific IgE (immunoglobulin E) to birch (≥ IgECAP(quantitative test that measures the overall quantity of circulating IgE in theblood) class 2; ≥0.70 kU/L) at screening.

• Non-allergic control group: A documented negative clinical history for allergicrhinitis, negative SPT response (wheal diameter <3 mm) and negative sIgE (IgE CAPclass 0) to birch pollen (birch), grasses, house dust mite, cat, horse, dog,ragweed, mugwort and mould (Alternaria alternata).

Exclusion Criteria:

• A subject in the birch pollen allergy group with rhinitis and/or conjunctivitiscaused by animal hair and dander to which the subject is regularly exposed is noteligible for the trial. In terms of seasonal and perennial allergens like mouldsetc. the subject can be sensitised to these allergens but is not eligible for thetrial if the subject has symptoms induced by these allergens during the trialperiod.

• Patients who have experienced a severe asthma exacerbation within the last 3 months.

• Reduced lung function (in adults: FEV1 (Forced Expiratory Volume 1 sec) < 70% ofpredicted value after adequate pharmacologic treatment).

• SLIT (sublingual immunotherapy) treatment with birch pollen for more than 1 monthwithin the last 5 years. In addition, any SLIT treatment with birch pollen withinthe previous 12 months.

• SCIT (subcutaneous immunotherapy) treatment with birch pollen reaching themaintenance dose within the last 5 years. In addition, any SCIT treatment with birchpollen within the previous 12 months.

• Ongoing treatment with any allergy immunotherapy product

• Has any nasal oropharyngeal condition that might mimic birch pollen allergy symptoms (e.g. strong septal deviation, nasal polyps, a history of paranasal sinus surgery orsurgery of nasal turbinate's; choanal atresia, hypertrophy of pharyngeal tonsil,naso/oropharyngeal tumours, hypertrophy of palatial tonsils). For exclusion bothsided nasal endoscopy including endoscopy of the epipharynx is required.

• Any general condition that might induce birch pollen allergy symptoms (hypothyroidism, pregnancy).

• Any pharmacotherapy that might induce birch pollen symptoms (e.g. treatment withantihypertensive drugs, treatment with cholinergic acting drugs likeantidepressants).

• History of any other (allergic) rhinitis symptoms than to birch pollen during thewhole study period for subjects in the birch pollen allergy group.

• A relevant history of systemic allergic reaction e.g. anaphylaxis withcardiorespiratory symptoms, generalised urticaria or severe facial angioedema thatin the opinion of the investigator may constitute an increased safety concern.

• Any clinically relevant chronic disease incl. malignancy that in the opinion of theinvestigator would interfere with the trial evaluations or the safety of thesubject.

• Active or poorly controlled autoimmune diseases, immune defects, immunodeficiencies,immunosuppression or malignant neoplastic diseases with current disease relevance.

• Immunosuppressive treatment (ATC code L04 or L01) within 3 months prior to thescreening visit.

·-Treatment with medications with potential impact on NAC (e.g. treatment withanti-IgE or anti IL-5 (interleukin 5) drugs within 130 days/5 half-lives of the drug (which ever longest) or treatment with antidepressant or antipsychotic medicationswith antihistaminic effect).

• Current participation in other clinical trials and or use of an investigational drugwithin 30 days/5 half-lives of the drug, which ever the longest, prior to screening.

• A history of allergy, hypersensitivity or intolerance to the IMP (investigationmedicinal product) (except birch pollen).

• Smoking / significant history of smoking.

• A history of alcohol or drug abuse