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

Study Overview
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Brief Summary
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This Phase 3 study is a randomized, observer-blind study of aQIV (an MF59-adjuvanted quadrivalent influenza vaccine) compared with a non-adjuvanted quadrivalent influenza vaccine (QIV) in adults ≥65 years of age. The aim of the study is to evaluate aQIV compared with QIV in the prevention of reverse transcription-polymerase chain reaction (RT-PCR)-confirmed influenza A and/or B in subjects ≥65 years of age.

Official Title
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A Phase 3/3b, Randomized, Observer-blind, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of an MF59-Adjuvanted Quadrivalent Subunit Inactivated Influenza Vaccine Compared to a Quadrivalent Influenza Vaccine in Adults ≥65 Years of Age

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: aQIV
* Biological: QIV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to participate in this study, all subjects must meet ALL of the inclusion criteria described. Adults of ≥65 years of age on the day of vaccination. 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. 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: Bedridden subjects (i.e. confined to bed by sickness or old age). Subjects that are incapacitated and because of that in need of a Legally Authorized Representative. Receipt of any influenza vaccine within 6 months prior to enrollment or any plan to receive influenza vaccine while participating in the study. 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. Known history of Guillain-Barré syndrome or another demyelinating disease such as encephalomyelitis and transverse myelitis. Clinical conditions representing a contra-indication to intramuscular administration of vaccines or blood draw. Abnormal function of the immune system resulting from: Clinical conditions; 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; Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent. Receipt of immunoglobulins or any blood products within 180 days prior to informed consent. 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. Acute (severe) febrile illness. 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. Study personnel or immediate family members (brother, sister, child, parent) or the spouse of study personnel. Participation in the current study for more than one season.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aQIV<br>MF59-adjuvanted QIV containing 2 influenza type A strains and 2 influenza type B strains | Biological: aQIV<br>* Participants receive a 0.5-mL intramuscular dose of aQIV 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). The strain composition is that recommended by the World Health Organization (WHO) for quadrivalent influenza vaccines contemporaneous to the timing of the study.<br>* Other names: Fluad Tetra/Quadrivalent;|
| Other: Comparator QIV<br>Non-adjuvanted QIV containing 2 influenza type A strains and 2 influenza type B strains | Biological: QIV<br>* Participants receive a 0.5-mL intramuscular dose of the non-adjuvanted QIV 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). The strain composition is that recommended by the WHO for quadrivalent influenza vaccines contemporaneous to the timing of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | ILI = influenza-like illness; RT-PCR = reverse transcription-polymerase chain reaction | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Endpoint: First-occurrence of 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 | CDC = Centers for Disease Control and Prevention | 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 WHO ILI definition | WHO = World Health Organization | 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 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 | 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. | Day 1 and Day 22 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Vaccine, MF59 adjuvant, aQIV, A/H1N1, A/H3N2, B/Yamagata, B/Victoria