Study to evaluate the effect of different pre-seasonal BM32 dosing schedules on the induction of a protective allergen-specific IgG Immune response

INTERVENTION: Product Code: BM32 Pharmaceutical Form: Suspension for injection INN or Proposed INN: BM321 Current Sponsor code: BM321 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 100‐ INN or Proposed INN: BM322 Current Sponsor code: BM322 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 100‐ INN or Proposed INN: BM325 Current Sponsor code: BM325 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 100‐ INN or Proposed INN: BM326 Current Sponsor code: BM326 Concentration unit: µg/ml microgram(s)/millilitre Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Suspension for injection Route of administration of the placebo: Subcutaneous use Trade Name: Physiologische Kochsalzlösung Fresenius Product Name: Physiologische Kochsalzlösung Fresenius Pharmaceutical Form: Solution for injection INN or Proposed INN: Sodium Chloride Other descriptive name: NaCl Concentration unit: % percent Concentration type: equal Concentration number: 0.9‐ CONDITION: Grass pollen allergy Therapeutic area: Diseases [C] ‐ Ear, nose and throat diseases [C09] PRIMARY OUTCOME: Main Objective: To assess the level of allergen‐specific IgG4 and IgG1 antibodies at the peak of the grass pollen season comparing the different dosing schedules of BM32 at the dose of 20µg per API with placebo. Primary end point(s): • Level of allergen‐specific IgG4 antibodies at the peak of the grass pollen season ; (Visit 8) comparing the sum of IgG levels against Phl p 1 + Phl p 5 of each BM32 group vs. placebo. ; • Level of allergen‐specific IgG1 antibodies at the peak of the grass pollen season ; (Visit 8) comparing the sum of IgG levels against Phl p 1 + Phl p 5 of each BM32 group vs. placebo. ; Secondary Objective: • effects of different dosing schedules of BM32 (at a dose of 20µg per API) compared to placebo by studying the grass pollen‐specific Total Nasal Symptom Score (TNSS) of grass pollen‐induced allergic rhinitis provoked by spending 6 hours in the VCC before the treatment, and at Visit 9. ; • effect of treatment with different dosing schedules of BM32 on the Symptom‐Scores (SS), Medication‐Scores (MS) and Combined Symptom/Medication Scores (SMS) recorded in the Patient Diary during the peak of the grass pollen season. ; • Effect of treatment with BM32 dosing schedules on the “Well‐being” of subjects during the grass pollen season as measured via a visual analogue score (VAS) recorded in the Patient Diary. ; • Development of immunological parameters during the study by measuring grass pollen allergen‐specific IgG, IgG1, IgG4 in serum samples collected from subjects at different time points. ; • Relative safety and tolerability of the different BM32 dosing schedules vs. placebo. ; Timepoint(s) of evaluation of this end point: Visit 3 (baseline levels, before treatment); Visit 8 (at the peak of the grass pollen season) SECONDARY OUTCOME: Secondary end point(s): • Difference in the total Nasal Symptom Score (TNSS) (nasal obstruction, rhinorrhea, itchy nose and sneezing) between spending 6 hours in the VCC at Visit 2 and spending 6 hours in the VCC at Visit 9.; • The mean daily Symptom‐Score (SS), Medication‐Score (MS), and Combined Symptom‐/ Medication Score (SMS) measured during the grass pollen season and the peak of the grass pollen season.; • Mean level of “well‐being” during the grass pollen season of patients receiving BM32 compared to placebo based on daily records on a visual analogue score (VAS); • Mean allergen‐specific antibodies (IgG. IgG1, IgG4) as measured at different time points during the study (Visits 1,3,4,5,6,7,8, 9, 10, and 11) compared between verum treated and placebo treated patients.; • Frequency of AEs concerning occurrence, seriousness, intensity and relationship to study drug.; • Frequency and grading of SIT‐specific local and systemic reactions.; • Lung function (FEV1), blood pressure, pulse rate, body temperature, and breathing frequency at screening, and throughout the study ; • Findings of physical examination at screening, and at the follow‐up Visit; ; ; Timepoint(s) of evaluation of this end point: Efficacy endpoints will be evaluated during the peak of the grass pollen season or after the grass pollen season (visit 9) respectively.; Immunogenicity endpoints and safety endpoints will be evaluated throughout the study. INCLUSION CRITERIA: • The subjects are grass pollen allergic but otherwise healthy. Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history (including family), physical examination, laboratory studies, and other tests. • They are aged 18 to 60 years inclusive. • They have a history of seasonal allergic rhinitis (SAR) to grass pollen. • They have a normal electrocardiogram without clinically significant abnormalities. • They exhibit a moderate to severe response to approximately 1500 grass pollen grains/m3 within the first 2 hours in the Vienna Challenge Chamber, which is defined as a nasal symptom score (TNSS) of at least 6. (Nasal symptom score is the sum of nasal obstruction, rhinorrhea, itchy nose and sneezing, each of which have been scored on a categorical scale from 0 to 3 as given in Appendix II). • They have a positive skin prick test with a wheal diameter over 4mm for gr