SUBLIVAC FIX Birch Dose Tolerability/Dose Range Finding

Inclusion criteria

• Signed informed consent
• Age ≥ 18 ≤ 60 years
• Allergic rhinitis/rhinoconjunctivitis related to birch pollen with or without concomitant mild to moderate persistent asthma
• FEV1 > 70% for patients with a history of asthma, FEV > 70% or PEF > 80% for patients without a history of asthma
• A positive SPT (mean wheal diameter ≥ 3mm compared to negative control and negative control should be negative) for birch pollen assessed within

1 year before randomization.

• Positive serum specific anti-birch IgE-test (> 0.7 U/mL)
• A positive TNPT for birch pollen at screening (Lebel score ≥ 6) at

• 10,000 AU/mL

Exclusion criteria

• Patients with (expected) clinically relevant symptoms during the course of the trial due to concomitant sensitization i.e. positive SPT (mean wheal diameter ≥ 3mm) to allergens other than birch pollen
• Patients sensitized to pets should not be included if they are regularly exposed to pets and are symptomatic upon exposure to pets
• Completed immunotherapy (SCIT or SLIT) with birch pollen allergens within the past 5 years
• Completed unsuccessful specific immunotherapy in the past
• Vaccination within one week before start of therapy or during the initiation phase
• Anti-IgE therapy within the 6 months prior to inclusion and during the study
• Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
• Active malignancies or any malignant disease during the previous 5 years
• Severe uncontrolled diseases that could increase the risk for patients participating in the study, including but not limited to: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine diseases, clinically significant renal or hepatic diseases, or haematological disorders
• Active inflammation or infection of the target organs (nose, eyes or lower airways) at the start of the study
• Moderate to severe nasal obstructive diseases that preclude a TNPT (septal deviation, nasal polyps, recent nasal surgery, etc.)
• Diseases with a contraindication for the use of Adrenaline (e.g. hyperthyroidism, glaucoma)
• Use of systemic steroids within 4 weeks before start of the study and during the study
• Treatment with systemic and local β-blockers
• Participation in a clinical study with a new investigational drug within the last 3 months or for a biological within the last 6 months prior to or during the study
• Pregnancy, lactation or inadequate contraceptive measures for women of child-bearing age (adequate contraceptive measures will be the use of a contraceptive device or -pill)
• Alcohol, drug or medication abuse within the past year
• Any clinically significant abnormal laboratory parameter at screening
• Lack of cooperation or compliance
• Severe psychiatric, psychological, or neurological disorders
• Patients who are employees of the institution or 1st grade relatives or partners of the investigator