Monocenter 6-period Study in Patients With Seasonal Allergic Rhinitis to Birch Pollen to Establish a Challenge Model With Natural Birch Pollen in an Environmental Challenge Chamber (ECC)

Male and female subjects aged 18-65 years.

• Non smokers or ex-smokers with a history of less than 10 pack years, having been non-smokers for at least the last 12 months.
• History of allergic rhinitis to birch pollen. Subjects with mild intermittent asthma controlled with occasional use of as-needed short-acting beta-agonists can be included.
• Normal lung function (FEV1 ≥ 80 % predicted)
• Positive skin prick test for birch
• Able and willing to give written informed consent to take part in the study.
• Available to complete all study measurements
• Women will be considered for inclusion if they are:

O Not pregnant, as confirmed by pregnancy test (see flow chart) and not nursing.

O Of non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who were pre-menarchial or post-menopausal, with documented proof of hysterectomy or tubal ligation, or met clinical criteria for menopause and had been amenorrhoeic for more than 1 year prior to the screening visit).

O Of childbearing potential and using a highly effective method of contraception during the entire study (vasectomised partner, sexual abstinence - the lifestyle of the female should be such that there was complete abstinence from intercourse from two weeks prior to the first dose of study medication until at least 72 hours after treatment -, implants, injectables, combined oral contracep-tives, hormonal IUDs or double-barrier methods, i.e. any double combination of IUD, condom with spermicidal gel, diaphragm, sponge, and cervical cap).

Exclusion Criteria:

• History of a respiratory tract infection and/or exacerbation of asthma within 4 weeks before the screening.
• Any history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
• Administration of oral, injectable or dermal corticosteroids within 8 weeks or intranasal and/or inhaled corticosteroids 4 weeks prior to enrollment.
• Past or present disease, which as judged by the investigator, might have affected the outcome of this study. These diseases included, but were not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, hematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, tuberculosis, bronchiectasis or cystic fibrosis).
• Any structural nasal abnormalities or nasal polyps on examination, history of frequent nose bleeding or recent nasal surgery.
• Conditions or factors, which made the subject unlikely to be able to stay in the Fraunhofer ECC for four hours.
• Specific Immunotherapy (SIT) within the last two years prior to screening
• Risk of non-compliance with study procedures
• Participation in another clinical trial 30 days prior to enrolment
• Any contraindication for adrenalin use (e.g. use of local and systemic beta-blockers)
• History of drug or alcohol abuse