SUBLIVAC FIX Birch Phase III Short-term Efficacy

Inclusion criteria

• Signed informed consent
• Age ≥ 18 and ≤65 years
• Moderate-to-severe birch pollen induced allergic rhinitis/rhinoconjunctivitis based on ARIA classification for at least 2 consecutive years
• FEV1 (forced expiratory volume at one second) > 70% (of predicted value) for patients with a history of asthma, FEV1 > 70% or PEF (peak expiratory flow) > 80% (of predicted value) for patients without a history of asthma
• Positive SPT (skin prick test) for birch pollen (mean wheal diameter ≥ 3mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter ≥ 3mm)) assessed during screening.
• Serum specific anti-birch IgE (immunoglobulin E) concentration >0.7 U/ml
• Patients should be willing and capable to complete an e-diary daily during the birch pollen season (≥ 60% compliance in completion between Visit 1 and 2).
• A positive Nasal Provocation Test to birch pollen at Visit 2 (Lebel score ≥ 6) or a documented positive test within 1 year before start of treatment

Exclusion criteria

• Patients sensitized and symptomatic to pets should not be included if they are regularly exposed to pets
• Specific immunotherapy (SCIT or SLIT) with birch pollen or a cross-reacting allergen within the last 5 years
• SPT positive (mean wheal diameter ≥ 3mm compared to negative control; negative control should be negative; histamine control should be positive (mean wheal diameter ≥ 3mm)) patients to allergen(s) other than birch pollen, in the absence of a negative provocation test for this allergen(s) (within 1 year), who are expected to have clinically relevant symptoms during the birch pollen season
• Completed unsuccessful allergen-specific immunotherapy (SCIT or SLIT) within the last 5 years
• (Ongoing) allergen-specific immunotherapy (SCIT or SLIT) with any allergen(s) during the study period
• Vaccination one week before start of treatment and/or during the up-dosing phase
• Treatment with experimental products within the last 3 months or biologicals (including anti-IgE or TNF (tumor necrosis factor) - α treatment) within the last 6 months or during the study
• Uncontrolled asthma or other active respiratory diseases
• Clinically significant chronic sinusitis, ocular infection or severe inflammation of the oral mucosa
• Severe immune disorders (including auto-immune diseases) and/or diseases requiring immunosuppressive drugs
• Active malignancies or any malignant disease in the last 5 years
• Acute or chronic disease that in the opinion of the investigator is an additional risk for the patients, including but not limited to the following: cardiovascular insufficiency, any severe or unstable lung diseases, endocrine disorders, clinically significant renal or hepatic diseases, or haematological disorders
• Diseases with a contra-indication for the use of adrenaline (e.g. hyperthyroidism, glaucoma)
• Use of systemic corticosteroids 4 weeks before the study
• Treatment with systemic or local β-blockers
• Known hypersensitivity to any of the excipients (Disodium phosphate dihydrate, Sodium dihydrogen phosphate dehydrate, aminocaproic acid, Peppermint oil, Caramel Colorant or Glycerol)
• A positive urine pregnancy test, lactation or inadequate contraceptive methods (adequate methods: oral contraceptives, IUD (intrauterine device), condom use and having no sexual relationship with a man)
• Alcohol-, drug or medication abuse
• Lack of co-operation or compliance
• Severe psychiatric, psychological, or neurological disorders
• Any physical or mental condition that precludes administration or allergen-specific immunotherapy, compliance or participation in a clinical trial
• Patients who are employees of the department, 1st grade relatives, or partners of the investigator
• Patients who have planned holidays outside the country for more than 7 continuous days during the defined pollen season (1st of March till 31st of May)