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 onARIA classification for at least 2 consecutive years

• FEV1 (forced expiratory volume at one second) > 70% (of predicted value) for patientswith a history of asthma, FEV1 > 70% or PEF (peak expiratory flow) > 80% (of predictedvalue) for patients without a history of asthma

• Positive SPT (skin prick test) for birch pollen (mean wheal diameter ≥ 3mm compared tonegative control; negative control should be negative; histamine control should bepositive (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 birchpollen 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 adocumented positive test within 1 year before start of treatment

Exclusion Criteria:

• Patients sensitized and symptomatic to pets should not be included if they areregularly exposed to pets

• Specific immunotherapy (SCIT or SLIT) with birch pollen or a cross-reacting allergenwithin the last 5 years

• SPT positive (mean wheal diameter ≥ 3mm compared to negative control; negative controlshould be negative; histamine control should be positive (mean wheal diameter ≥ 3mm))patients to allergen(s) other than birch pollen, in the absence of a negativeprovocation test for this allergen(s) (within 1 year), who are expected to haveclinically 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) duringthe 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 6months or during the study

• Uncontrolled asthma or other active respiratory diseases

• Clinically significant chronic sinusitis, ocular infection or severe inflammation ofthe oral mucosa

• Severe immune disorders (including auto-immune diseases) and/or diseases requiringimmunosuppressive 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 riskfor the patients, including but not limited to the following: cardiovascularinsufficiency, any severe or unstable lung diseases, endocrine disorders, clinicallysignificant 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, Sodiumdihydrogen phosphate dehydrate, aminocaproic acid, Peppermint oil, Caramel Colorant orGlycerol)

• A positive urine pregnancy test, lactation or inadequate contraceptive methods (adequate methods: oral contraceptives, IUD (intrauterine device), condom use andhaving 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-specificimmunotherapy, compliance or participation in a clinical trial

• Patients who are employees of the department, 1st grade relatives, or partners of theinvestigator

• Patients who have planned holidays outside the country for more than 7 continuous daysduring the defined pollen season (1st of March till 31st of May)