A Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of an Adjuvanted Influenza Vaccine Compared to a Non-adjuvanted Influenza Vaccine in Adults ≥65 Years of Age

• aQIV or aTIV (Biological), also known as Fluad Tetra/Quadrivalent or Fluad: Participants receive a 0.5-mL intramuscular dose of aQIV or aTIV on Day 1. A 0.5 mL dose of aQIV contains nominally 15 µg of hemagglutinin (HA) of each of the 2 influenza type A strains and each of the 2 influenza B strains (total of 60 µg HA). A 0.5 mL dose of aTIV contains nominally 15 µg of HA of each of the 2 influenza type A strains and of the influenza B strain (total of 45 µg HA). The strain composition of aQIV and aTIV is that recommended by the World Health Organization (WHO) for quadrivalent and trivalent influenza vaccines, respectively, contemporaneous to the timing of the study.
• QIV or TIV (Biological): Participants receive a 0.5-mL intramuscular dose of the non-adjuvanted QIV or TIV on Day 1. A 0.5 mL dose of QIV contains nominally 15 μg of HA of each of the 2 influenza type A strains and each of the 2 influenza B strains (total of 60 μg HA). A 0.5 mL dose of TIV contains nominally 15 μg of HA of each of the 2 influenza type A strains and of the influenza B strain (total of 45 μg HA). The strain composition of QIV and TIV is that recommended by the WHO for quadrivalent and trivalent influenza vaccines, respectively, contemporaneous to the timing of the study.

Primary outcomes

• Efficacy Endpoint: First-occurrence of RT-PCR-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), using the protocol-defined ILI definition [From 14 days after vaccination (ie study day 15) and until the end of influenza season (typically end of May for Northern Hemisphere [NH] influenza season and end of November for Southern Hemisphere [SH] influenza season)]: ILI = influenza-like illness; RT-PCR = reverse transcription-polymerase chain reaction

Secondary outcomes

• Efficacy Endpoint: First-occurrence of RT-PCR-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), using the protocol-defined ILI definition [From 14 days after vaccination (ie study day 15) and until the end of influenza season (typically end of May for NH influenza season and end of November for SH influenza season)]
• Efficacy Endpoint: First-occurrence of culture-confirmed influenza, due to influenza Type A and/or B virus antigenically matched to the vaccine strains selected for the seasonal vaccine, using the protocol-defined ILI definition [From 14 days after vaccination (ie study day 15) and until the end of influenza season (typically end of May for NH influenza season and end of November for SH influenza season)]
• Efficacy Endpoint: First-occurrence of culture-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), using the protocol-defined ILI definition [From 14 days after vaccination (ie study day 15) and until the end of influenza season (typically end of May for NH influenza season and end of November for SH influenza season)]
• Efficacy Endpoint: First-occurrence of RT-PCR-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), using the modified CDC ILI definition [From 14 days after vaccination (ie study day 15) and until the end of influenza season (typically end of May for NH influenza season and end of November for SH influenza season)]: CDC = Centers for Disease Control and Prevention
• Efficacy Endpoint: First-occurrence of RT-PCR-confirmed influenza, due to any influenza Type A and/or B virus (regardless of antigenic match), using the WHO ILI definition [From 14 days after vaccination (ie study day 15) and until the end of influenza season (typically end of May for NH influenza season and end of November for SH influenza season)]: WHO = World Health Organization
• Efficacy Endpoint: First-occurrence of culture-confirmed influenza, due to influenza Type A and/or B virus antigenically unmatched to the vaccine strains selected for the seasonal vaccine, using the protocol-defined ILI definition [From 14 days after vaccination (ie study day 15) and until the end of influenza season (typically end of May for NH influenza season and end of November for SH influenza season)]
• Immunogenicity Endpoint: Pre- and post-vaccination hemagglutination inhibition (HI) geometric mean titers (GMTs) for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains [Day 1 and Day 22]
• Immunogenicity Endpoint: Geometric mean fold increase (GMFI, Day 22/Day1) for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains [Day 1 and Day 22]
• Immunogenicity Endpoint: Percentage of subjects achieving seroconversion for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains [Day 1 and Day 22]: Seroconversion is defined as the percentage of subjects with either a pre-vaccination titer <1:10 and a post-vaccination titer ≥1:40 or a pre-vaccination titer ≥1:10 and a ≥4-fold increase in post-vaccination titer.
• Immunogenicity Endpoint: Percentage of subjects with HI titer ≥1:40 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria vaccine strains [Day 1 and Day 22]
• Safety Endpoint: All adverse events (AEs) reported within 30 minutes after vaccination [Day 1]
• Safety Endpoint: Serious adverse events (SAEs) reported during the entire study period [Day 1 to Day 181 or the end of the influenza season, whichever is longer]
• Safety Endpoint: Adverse events of special interest (AESIs) reported during the entire study period [Day 1 to Day 181 or the end of the influenza season, whichever is longer]
• Safety Endpoint: AEs leading to premature withdrawal from the study during the entire study period [Day 1 to Day 181 or the end of the influenza season, whichever is longer]

Sex: All, ages: 65 Years to any, accepts healthy volunteers

Inclusion Criteria:

In order to participate in this study, all subjects must meet ALL of the inclusion criteria described.

1. Adults of ≥65 years of age on the day of vaccination.
2. Individuals who have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
3. Individuals who have the ability to comply with study procedures including follow-up.

Exclusion Criteria:

In order to participate in this study, all subjects must not meet any of the exclusion criteria described below:

1. Bedridden subjects (i.e. confined to bed by sickness or old age).
2. Subjects that are incapacitated and because of that in need of a Legally Authorized Representative.
3. Receipt of any influenza vaccine within 6 months prior to enrollment or any plan to receive influenza vaccine while participating in the study.
4. Hypersensitivity, including allergy, to any component of vaccines whose use is foreseen in this study, or severe allergic reaction (e.g. anaphylaxis) to previous influenza vaccination.
5. Known history of Guillain-Barré syndrome or another demyelinating disease such as encephalomyelitis and transverse myelitis.
6. Clinical conditions representing a contra-indication to intramuscular administration of vaccines or blood draw.
7. Abnormal function of the immune system resulting from:

   1. Clinical conditions;
   2. Systemic administration of corticosteroids (PO/IV/IM) at a dose ≥20 mg/day of prednisone (or equivalent) for more than 14 consecutive days within 90 days prior to informed consent; Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted;
   3. Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent.
8. Receipt of immunoglobulins or any blood products within 180 days prior to informed consent.
9. Receipt of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the study vaccination, or planned use during the entire study period.
10. Acute (severe) febrile illness.
11. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
12. Study personnel or immediate family members (brother, sister, child, parent) or the spouse of study personnel.

155 more sites not listed.

• Clinical Program Director, Study director, Seqirus