A multi-centre, double-blind dose-ranging study to evaluate

INTERVENTION: Product Name: POLLINEX Quattro® Birch Pharmaceutical Form: Suspension for injection INN or Proposed INN: birch pollen allergen extract Other descriptive name: BIRCH POLLEN MODIFIED ALLERGEN TYROSINE‐ADSORBED Concentration unit: SU/ml Standardised Unit(s)/millilitre (Deprecated) Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Product Name: POLLINEX Quattro® Birch Pharmaceutical Form: Suspension for injection INN or Proposed INN: birch pollen allergen extract Other descriptive name: BIRCH POLLEN MODIFIED ALLERGEN TYROSINE‐ADSORBED Concentration unit: SU/ml Standardised Unit(s)/millilitre (Deprecated) Concentration type: equal Concentration number: 300‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Product Name: POLLINEX Quattro® Birch Pharmaceutical Form: Suspension for injection INN or Proposed INN: birch pollen allergen extract Other descriptive name: BIRCH POLLEN MODIFIED ALLERGEN TYROSINE‐ADSORBED Concentration unit: SU/ml Standardised Unit(s)/millilitre (Deprecated) Concentration type: equal Concentration number: 800‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Product Name: POLLINEX Quattro® Birch Pharmaceutical Form: Suspension for injection INN or Proposed INN: birch pollen allergen extract Other descriptive name: BIRCH POLLEN MODIFIED ALLERGEN TYROSINE‐ADSORBED Concentration unit: SU/ml Standardised Unit(s)/millilitre (Deprecated) Concentration type: equal Concentration number: 2000‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Product Name: POLLINEX Quattro® Birch Pharmaceutical Form: Suspension for injection INN or Proposed INN: birch pollen allergen extract Other descriptive name: BIRCH POLLEN MODIFIED ALLERGEN TYROSINE‐ADS CONDITION: seasonal allergic rhinoconjunctivitis due to birch pollen ; MedDRA version: 17.1 Level: LLT Classification code 10001728 Term: Allergic rhinoconjunctivitis System Organ Class: 100000004853 Therapeutic area: Body processes [G] ‐ Immune system processes [G12] PRIMARY OUTCOME: Main Objective: The primary objective is to assess the difference in change (baseline to post‐treatment) in total symptom score (TSS) recorded following application of a CPT between four POLLINEX Quattro® Birch treatment arms of 600SU, 1550SU, 5100SU and 13600 (cumulative doses), respectively. Primary end point(s): Change from baseline to post‐treatment in TSS following CPT Secondary Objective: Efficacy:; 1. To compare proportions of subjects with negative CPT after treatment between four POLLINEX Quattro® Birch treatment arms; 2. To compare change (baseline to post‐treatment) in allergen concentration required for eliciting of a positive CPT ; 3. To compare change (baseline to post‐treatment) in individual symptom scores (ISS) between four POLLINEX Quattro® Birch treatment arms ; 4. To compare immunological (Birch specific IgG, IgG4 and IgE) differences (baseline to post‐treatment) between four POLLINEX Quattro® Birch treatment arms ; ; Safety/Tolerability:; 1. To compare the tolerability of different subcutaneous doses.; 2. To compare the tolerability of cumulative subcutaneous doses .; 3. To compare the frequency of adverse events (AEs).; 4. To compare the frequency of adverse reaction complexes (ARCs); 5. To compare the proportion of subjects not completing the treatment regimen due to AEs.; 6. To compare changes in routine clinical laboratory values and vital signs. Timepoint(s) of evaluation of this end point: Visit 2/2a (baseline) and Visit 8 (post‐treatment) SECONDARY OUTCOME: Secondary end point(s): Efficacy:; ? Proportion of subjects with negative CPT post‐treatment; ? Number of additional allergen concentration steps required to elicit a positive CPT post‐treatment; ? Change from baseline to post‐treatment in individual symptom scores (ISS) following CPT; ? Immunological changes to immunoglobulins (birch specific IgG, IgG4 and IgE); ; Safety:; ? Tolerability of different subcutaneous doses; ? Tolerability of cumulative subcutaneous doses (i.e. dose regimens); ? Frequency of AEs; ? Frequency of ARCs (the total of treatment related injection site and systemic AEs experienced by a subject within a 24‐hour period after an injection); ? Premature discontinuation from treatment or study due to AEs; ? Clinical laboratory values (chemistry, haematology, urinalysis); ? Vital signs; Timepoint(s) of evaluation of this end point: Efficacy:; ‐ Visit 8; ‐ Visit 8; ‐ V2/2a and V 8; ‐ V 1 and V 8; ; Safety:; during the whole course of the study; INCLUSION CRITERIA: 1. Aged 18 to 60 years inclusive. 2. Allergy to birch pollen allergen, defined by: • A positive case history of moderate to severe symptoms of seasonal allergic rhinoconjunctivitis ascribed to birch pollen exposure that required repeated use of antihistamines, nasal steroids, and/or leukotriene modifiers in at least the last 2 years; • A positive skin prick test (SPT) for birch pollen allergen (wheals of = 3 mm greater than the negative control after skin prick testing) at Visit 1. 3. Positive SPT to histamine [wheal (longest diameter) = 3 mm greater than the negative control]. 4. Negative SPT to the negative control (redness with wheal = 2 mm is acceptable). 5. Positive CPT at Visit 1 6. Forced expiratory volume (FEV) in 1 second (FEV1) = 80% of predicted, with a FEV1/forced vital capacity (FVC) ratio = 70%. 7. Adhere to the drug washout times prior to Screening (Visit 1 and 1a, if applicable).