A Clinical Study to Evaluate the Immunogenicity and Safety of an Adjuvanted Quadrivalent Influenza Vaccine Compared With a Licensed Quadrivalent Vaccine in Adults 50 to 64 Years of Age

Study Overview
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Brief Summary
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This Phase 3 study is a randomized, observer-blind immunogenicity and safety study of aQIV (an MF59-adjuvanted quadrivalent influenza vaccine) compared with a licensed quadrivalent influenza vaccine in adults 50 to 64 years of age.

Official Title
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A Phase 3, Randomized, Observer-blind, Controlled, Multicenter, Clinical Study to Evaluate Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Subunit Inactivated Influenza Vaccine in Comparison With a Licensed Quadrivalent Influenza Vaccine, in Adults 50 to 64 Years of Age

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: aQIV
* Biological: Comparator 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 following inclusion criteria: Individuals 50 to 64 years of age (i.e. 50 to ≤64 years) on the day of informed consent Individuals who have voluntarily given written consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry Individuals who can comply with study procedures including follow-up Males, females of non-childbearing potential or females of childbearing potential who are using an effective birth control method, at least 30 days prior to informed consent, which they intend to use for at least 2 months after the study vaccination Exclusion Criteria: In order to participate in this study, all subjects must not meet ANY of the exclusion criteria described below: Females of childbearing potential who are pregnant, lactating, or who have not adhered to a specified set of contraceptive methods from at least 30 days prior to study entry and who do not plan to do so until 2 months after the study vaccination Progressive, unstable or uncontrolled clinical conditions Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study History of any medical condition considered an AESI Known history of Guillain Barré syndrome or another demyelinating disease such as encephalomyelitis and transverse myelitis Clinical conditions representing a contraindication to intramuscular vaccination and blood draws Abnormal function of the immune system resulting from: Clinical conditions Systemic administration of corticosteroids (PO/IV/IM) at a dose equivalent to ≥20 mg/day of prednisone 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 is also permitted Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent Received immunoglobulins or any blood products within 180 days prior to informed consent Received an investigational or non-registered medicinal product within 30 days prior to informed consent, or who are unwilling to refuse participation in another clinical study at any time during the conduct of this study (notes: i. concomitant participation in a study not involving or no longer involving administration of drugs, vaccines, or medical devices, is acceptable (e.g. studies in safety follow-up phase, observational studies); ii. concomitant participation in a COVID-19 vaccine study is acceptable provided that the vaccine dosing interval mentioned in Exclusion Criterion #11 is adhered to) Receipt of any influenza vaccine within 6 months prior to enrollment in this study, or plan to receive influenza vaccine during the study period Receipt of any (investigational or licensed) COVID-19 vaccine within 14 days (non-replicating vaccines) or 28 days (replicating vaccines) prior to enrollment or plan to receive any COVID-19 vaccine within 7 days from study vaccination Receipt of any inactivated non-influenza vaccine within 14 days or live-attenuated vaccine within 28 days prior to enrollment in this study or plan to receive any other non-influenza vaccine within 28 days from study vaccination 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 or household member of study personnel

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 64 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>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<br>|
| Active Comparator: Comparator QIV<br>Non-adjuvanted comparator QIV containing 2 influenza type A strains and 2 influenza type B strains | Biological: Comparator QIV<br>* Participants receive a 0.5-mL intramuscular dose of Comparator QIV on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio of Hemagglutination Inhibition (HI) Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains | The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. | Day 22 | 
| Immunogenicity Endpoint: Seroconversion Rate (SCR) and SCR Difference for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains | The SCR defined as the percentage of subjects with either a prevaccination HI titer <1:10 and a postvaccination (Day 22) HI titer ≥1:40, or with either a prevaccination HI titer ≥1:10 and a ≥4-fold increase in postvaccination HI titer. The SCR difference is defined as the Comparator QIV SCR minus the aQIV SCR. | Day 1 to Day 22 | 
| Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains | The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. | Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains | The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. | Day 181 | 
| Immunogenicity Endpoint: GMT of HI Antibodies on Day 1, Day 22, and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains | GMTs on Day 1 (prior to vaccination), Day 22 (3 weeks after vaccination), and Day 181 (6 months after vaccination) as determined by HI assay against each of the four vaccine strains | Day 1 to Day 181 | 
| Immunogenicity Endpoint: Geometric Mean Fold Increase (GMFI) for Day 22/Day 1 and Day 181/Day 1 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains | The GMFI is defined as the geometric mean of the fold increase of postvaccination HI titer over the prevaccination HI titer. | Day 1 to Day 181 | 
| Immunogenicity Endpoint: The Percentage of Subjects With a Titer ≥1:40 at Day 1, Day 22, and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains | Percentage of subjects with a titer ≥1:40 on Day 1, Day 22, and Day 181 as determined by HI assay against each of the four vaccine strains | Day 1 to Day 181 | 
| Immunogenicity Endpoint: SCR at Day 22 and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains | The SCR defined as the percentage of subjects with either a prevaccination HI titer <1:10 and a postvaccination (Day 22 or Day 181) HI titer ≥1:40, or with either a prevaccination HI titer ≥1:10 and a ≥4-fold increase in postvaccination HI titer. | Day 1 to Day 181 | 
| Safety Endpoint: Solicited Local and Systemic AEs for 7 Days Following Vaccination | Number and percentage of subjects with solicited local and systemic AEs occurring for 7 days following vaccination | Day 1 through Day 7 | 
| Safety Endpoint: All Unsolicited AEs for 21 Days Following Vaccination | The percentage of subjects with at least one unsolicited AE occurring 21 days following vaccination The severity of AEs is based on the maximum severity associated with a Preferred Term for a reported AE. Related AEs include possibly related AEs, probably related AEs and AEs with missing relatedness assessment. The severity and relatedness of AEs were determined by the investigator. For the any AE summary by severity, a subject with multiple AEs is counted according to the highest severity of their reported AEs. | Day 1 through Day 22 | 
| Safety Endpoint: Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Withdrawal From the Study, and Adverse Events of Special Interest (AESIs) | The percentage of subjects with any SAE, AE leading to withdrawal, or AESI during the study period | Day 1 through Day 271 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Vaccine, MF59 adjuvant