Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of an MF59-Adjuvanted Quadrivalent Influenza Vaccine Compared to Non-influenza Vaccine Comparator in Adults ≥ 65 Years of Age

The primary efficacy endpoint was the time of first-occurrence of RT-PCR-confirmed influenza due to any strain of influenza regardless of antigenic match to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the primary endpoint.

Safety of vaccination was assessed in terms of percentage of subjects reporting solicited local and systemic AEs up to 7 days after vaccination.

Safety of vaccination was assessed in terms of percentage of subjects reporting medically attended AEs within 30 days after of first occurrence RT-PCR confirmed influenza.

Safety of vaccination was assessed in terms of percentage of subjects reporting unsolicited AEs up to 21 days after vaccination.

Safety of vaccination was assessed in terms of percentage of subjects reporting SAEs, AEs leading to withdrawal, NOCDs, and AESIs up to 366 days after vaccination.

The secondary efficacy endpoint was the time of first-occurrence of RT-PCR-confirmed influenza due to any strain of influenza regardless of antigenic match to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary efficacy endpoint.

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically matched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically matched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza regardless of antigenic match from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza regardless of antigenic match from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically unmatched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using protocol defined ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

The secondary efficacy endpoint was the time of first-occurrence of culture confirmed influenza due to any strain of influenza antigenically unmatched to the strains selected for the seasonal vaccine from Day 21 through 180 days after vaccination or end of the influenza season, whichever is longer, using modified CDC ILI definition. Absolute vaccine efficacy is VE=1-HR, where HR is the hazard ratio of aQIV vs non-influenza comparator estimated by the Cox proportional hazards model for the secondary endpoint.

The log-transformed antibody titers (GMT) at Day 1 and Day 22 were evaluated using an analysis of covariance (ANCOVA) model including factors for site/country, pre-vaccination titer, age, and comorbidity.

The GMR was assessed as the postvaccination HI titer divided by the prevaccination HI titer (Day 22/Day 1).

The percentage of subjects vaccinated with aQIV with a HI antibody titers ≥1:40 was assessed for each of the 4 strains Assessment criteria was considered fulfilled if the lower bound of the two-sided 95% CI for percent of subjects with HI antibody titer ≥1:40 met or exceeded 60% at Day 22.

The percentage of subjects achieving SCR at Day 22 was assessed for each of the 4 strains. SCR is defined as HI titer ≥1:40 for subjects seronegative at baseline (HI titer <1:10) or a minimum 4-fold increase in HI titer for subjects seropositive at baseline (HI titer ≥1:10) on Day 22. Assessment criteria was considered fulfilled if the lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody SCR met or exceeded 30% at Day 22.