Phase III, Stratified, Randomized, Controlled, Observer-Blind, Multicenter Study to Evaluate the Safety, Tolerability, and Immunogenicity of Two Doses of aH5N1 when Administered to Adult and Elderly Subjects With and Without Underlying Medical Conditions.

INTERVENTION: Trade Name: Aflunov Product Name: Aflunov Pharmaceutical Form: Suspension for injection in pre‐filled syringe Trade Name: Fluad Product Name: Fluad Pharmaceutical Form: Suspension for injection in pre‐filled syringe CONDITION: Pandemic Influenza ; MedDRA version: 18.0 Level: LLT Classification code 10070436 Term: H5N1 influenza System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] SECONDARY OUTCOME: Secondary end point(s): Secondary Immunogenicity Endpoints: ; ? Geometric mean titers (GMTs) at the following time points: day 1, day 22 (3 weeks after the first vaccination), day 43 (3 weeks after the second vaccination) as determined by HI and SRH ; ? GMRs, calculated as follows: day 22/day 1 as determined by HI and day 22/day 1, day 43/day 1 as determined by SRH ; ? Percentage of subjects achieving seroconversion (defined as HI =1:40 for subjects who were seronegative at baseline [day 1 HI titer <1:10] or a minimum 4 fold increase in HI titer for subjects who were seropositive at baseline [day 1 HI titer =1:10]) on days 22 ; ? Percentage of subjects with an HI titer =1:40 on days 1 and 22 ; ? Percentage of subjects achieving seroconversion (defined as SRH area =25 mm2 for subjects who were seronegative at baseline [day 1 SRH area =3.997 mm2] or a significant increase [at least 50% increase] in SRH area for subjects who were seropositive at baseline [SRH area >3.997 mm2]) on days 22, 43 ; ? Percentage of subjects with geometric mean area =25 mm2 on days 1, 22, 43 ; Timepoint(s) of evaluation of this end point: three weeks after first vaccination (day 22) by HI ; three weeks after first and second vaccinations (day 22 and day 43) by SRH INCLUSION CRITERIA: In order to participate in this study, all subjects must meet ALL of the following inclusion criteria in the “all subjects” section and ALL of the inclusion criteria in the respective section for their underlying health status: All subjects 1. Male and female individuals 18 years of age and older at the time of enrollment who are mentally competent, willing and able to understand the nature and risks of the proposed study, and able to sign the consent form prior to study entry; 2. Individuals with a projected life expectancy of 12 months or longer; 3. Individuals who are able to comply with all study procedures and requirements; Subjects with underlying medical conditions only 4. Individuals with at least one of the following medical conditions: a. Documented underlying chronic respiratory medical condition: Chronic pulmonary disease. Classification of severity of COPD will be based on utilization of the 2013 Global Initiative f PRIMARY OUTCOME: Main Objective: Primary Immunogenicity Objective: ; To evaluate homologous antibody responses to aH5N1 vaccine 3 weeks after second vaccination (day 43) according to CHMP immunogenicity criteria1 in adult (18 through 60 years of age) and elderly (=61 years of age) subjects who are healthy or with underlying medical condition, as measured by hemagglutination inhibition (HI) assay.; ; Primary Safety Objective: ; To evaluate in pooled age groups 18 years of age and older solicited and unsolicited adverse events in adults and elderly subjects who are healthy or with underlying medical condition who have received aTIV or aH5N1 vaccine. Primary end point(s): Primary Immunogenicity Endpoint:; ? Percentage of subjects achieving seroconversion (defined as HI =1:40 for subjects who were seronegative at baseline [day 1 HI titer <1:10] or a minimum 4‐fold increase in HI titer for subjects who were seropositive at baseline [day 1 HI titer =1:10]) on day 43; ? Geometric mean ratios (GMRs) on day 43/day 1, as determined by HI assay; ? Percentage of subjects with an HI titer =1:40 on day 43; ; Primary Safety Endpoint:; ? Percentages of subjects with solicited local, solicited systemic, and other AEs that occur within 7 days following each vaccination and calculated for 4 time intervals after vaccination: 30 minutes, 6 hours through 3 days, 4 days through 7 days, and 6 hours through 7 days; ? Percentages of subjects with any unsolicited AEs reported within 21 days after each vaccination within each vaccine group; ? Percentages of subjects reporting SAEs, NOCDs, medically attended AEs, AESIs, AEs leading to withdrawal from the study, and concomitant medications associated with these events, as collected from day 1 through day 202; ; Solicited local AEs will include injection‐site erythema, injection‐site induration, injection‐site ecchymosis, and injection‐site pain; solicited systemic AEs will include loss of appetite, nausea, fatigue, generalized myalgia, generalized arthralgia, headache, shivering/chills, vomiting, diarrhea, and body temperature =38.0°C (as measured orally). Secondary Objective: Secondary Immunogenicity Objectives: ; To evaluate homologous antibody responses to aH5N1 vaccine 3 weeks after first vaccination (day 22) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition, as measured by HI assay. ; ; To evaluate homologous antibody responses to aH5N1 vaccine 3 weeks after first and second vaccinations (day 22 and day 43) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition, as measured by serial radial haemolysis (SRH) assay. Timepoint(s) of evaluation of this end point: Primary Immunogenicity Endpoint: 3 weeks after second vaccination (day 43) by HI ; Primary Safety Endpoint: all timepoints