Phase III, Multicenter Study to Evaluate the Safety, immune response, and effectiveness of Two Doses of aH5N1 vaccine when Administered to Adult and Elderly Subjects With and Without Immunosuppresive Diseases

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 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] SECONDARY OUTCOME: Secondary end point(s): Secondary Immunogenicity Endpoints ; ‐ Geometric means 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 seropsitive 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: All subjects 1. Male and female individuals 18 years of age and older at the time of enrollment who are noninstitutionalized, 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 immunosuppressive conditions only 4. Individuals with a confirmed diagnosis of only one of the following medical conditions a. Transplant recipients: Adult subjects who have undergone prior renal, cardiac, liver, lung, or bone marrow transplantation, more than 3 months prior to enrollment b. HIV‐1 infected subjects: i. Adults with Confirmed Diagnosis of HIV‐1 infection ii. CD4+ cell count >200 per mm³ within 3 months prior to the study enrollment iii. HIV‐1 viral load under 200 copies 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 criteria in adult (18 through 60 years of age) and elderly (=61 years of age) subjects who are healthy or with immunosuppressive conditions, 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 immunosuppressive conditions who have received aTIV or aH5N1 vaccine; Primary end point(s): Primary 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 immunosuppressive conditions, 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 immunosuppressive conditions, 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