SUBLIVAC FIX Birch Dose Tolerability/Dose Range Finding

A Randomized, Double-blind, Placebo-controlled Study to Determine Safety, Tolerability and the Optimal Effective Dose of SUBLIVAC FIX Birch in Patients With Allergic Rhinitis/Rhinoconjunctivitis Caused by Birch Pollen

The aim of the study is to determine the optimal effective dose of SUBLIVAC FIX Birch based on reduction of upper airways reactivity after 5 months of treatment with different dosages of SUBLIVAC FIX Birch compared to placebo. Furthermore, safety and tolerability will be assessed by the number of related Adverse Events of different dosages of SUBLIVAC FIX Birch compared to placebo.

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