A Phase I/II, randomised, multicentre, placebo-controlled, partially-blinded, parallel-group study to assess the safety, tolerability and immune response following vaccination with ImmunoseTM FLU in older adults (age 50 to 75 years)

INTERVENTION: Product Name: Immunoseâ„¢ FLU 1%; quadrivalent inactivated split influenza antigen 30 µg HA/strain, 1% Endocine Pharmaceutical Form: Nasal drops Pharmaceutical form of the placebo: Nasal drops Route of administration of the placebo: Nasal use Product Name: Immunoseâ„¢ FLU 2%; quadrivalent inactivated split influenza antigen 30 µg HA/strain, 2% Endocine Pharmaceutical Form: Nasal drops Pharmaceutical form of the placebo: Nasal drops Route of administration of the placebo: Nasal use Product Name: Immunoseâ„¢ FLU 2%, 300 µl; quadrivalent inactivated split influenza antigen 30 µg HA/strain, 2% Endoc Pharmaceutical Form: Nasal drops Pharmaceutical form of the placebo: Nasal drops Route of administration of the placebo: Nasal use Product Name: Influenza antigen; quadrivalent inactivated split, 30 µg HA/strain Pharmaceutical Form: Nasal drops Pharmaceutical form of the placebo: Nasal drops Route of administration of the placebo: Nasal use Product Name: Influsplit Tetra and ImmunoseTM FLU 2% Pharmaceutical Form: Injection Trade Name: Influsplit Tetra Product Name: Influsplit Tetra; quadrivalent inactivated split influenza antigen 15 µg HA/strain Pharmaceutical Form: Injection CONDITION: Influenza ; MedDRA version: 20.0 Level: PT Classification code 10022000 Term: Influenza System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: ; Primary end point(s): 1. Type and incidence of AEs and SAEs from the time of first study drug administration (Visit 2) until the last visit to the clinic (Visit 4 for group 1 to 6 and Visit 3 for group 7). ; 2. Type and incidence of SAEs and AEs of special interest during the 6 months safety follow‐up. ; 3. Frequency and severity of discomfort in the nose and throat and/or arm before study drug administration and 15, 30, 60 and 120 minutes after study drug administration. Discomfort in the nose and throat (group 1‐6) and/or arm (group 6‐7) will be assessed using a non‐graded 100 mm visual analogue scale (VAS).; 4. Frequency of clinically significant changes in ECG, vital signs, physical examination findings and laboratory variables from baseline to the last visit to the clinic.; ; Secondary Objective: To evaluate the immune response to Immunoseâ„¢ FLU based on Endocineâ„¢ and quadrivalent influenza antigens in older adults by measurement of haemagglutination‐inhibition (HI), virus neutralization (VN) and single radial haemolysis (SRH) titres in serum, and immunoglobulin A (IgA) titers in nasal secretions.; ; Timepoint(s) of evaluation of this end point: 1. Visit 2 and until the last visit to the clinic (Visit 4 for group 1 to 6 and Visit 3 for group 7). ; 2. During the 6 months safety follow‐up.; 3. Before study drug administration and 15, 30, 60 and 120 minutes after study drug administration.; 4. From baseline to the last visit to the clinic.; Main Objective: To evaluate the safety and tolerability of Immunoseâ„¢ FLU based on Endocineâ„¢ and quadrivalent influenza antigens in older adults (50 to 75 years). SECONDARY OUTCOME: ; Secondary end point(s): 1. Measurement of HI in blood, including: ; ‐ Geometric mean titres (GMTs) and pre‐/post‐treatment ratios (GMRs) ; ‐ Percentage of subjects with seroprotection (i.e., an HI titre =40) at pre‐treatment and 21 days after each treatment. ; ‐ Percentage of subjects with seroconversion (i.e., either a pre‐treatment HI titre <10 and a post‐treatment titre =40 or a pre‐treatment HI titre =10 and a fourfold increase in titre) at pre‐treatment and 21 days after each treatment. ; ; 2. Measurement of VN titres in blood (pre‐treatment and 21 days after each treatment) ; ‐ GMTs and pre‐/post‐treatment GMRs ; ; 3. Analysis of SRH in blood, including: ; ‐ GMTs and pre‐/post‐treatment GMRs ; ‐ Percentage of subjects with seroprotection (i.e., a SRH titre >25 mm2) at pre‐treatment and 21 days after each treatment. ; ‐ Percentage of subjects with seroconversion (i.e., either a negative pre‐treatment serum (<4 mm2) and a positive post‐treatment serum [area =25 mm2] or a significant increase in antibody titre i.e. at least a 50% increase in post‐treatment area if pre‐treatment is not negative). ; ; 4. Measurement of influenza‐specific IgA in nasal secretions (pre‐treatment and 21 days after each treatment) ; ‐ GMTs and pre‐/post‐treatment GMRs ; ‐ Percentage of subjects with a 2‐fold, 4‐fold and 8‐fold increase in influenza‐specific IgA ; ; Timepoint(s) of evaluation of this end point: 1. At pre‐treatment and 21 days after each treatment. ; 2. At pre‐treatment and 21 days after each treatment. ; 3. At pre‐treatment and 21 days after each treatment. ; 4. At pre‐treatment and 21 days after each treatment. ; INCLUSION CRITERIA: 1. Signed informed consent prior to any study related procedures. 2. Male or female 50‐75 years of age (both inclusive) at screening. 3. Subjects who the Investigator believes will comply with the requirements of the protocol. 4. Judged by the Investigator to have no serious illness based on medical history, physical examination, ECG, vital signs and blood and urine assessments at screening. 5. All females should have been post‐menopausal for at least 12 months or use a highly effective contraceptive method to prevent pregnancy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age rang