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

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

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.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: aQIV; Biological: Comparator QIV

• Study Type: Interventional
• Enrollment (Actual): 2044
• Phase: Phase 3

Contacts and Locations

Study Locations

• Estonia
  • Paide, Estonia
    • 23302 Vee Family Doctors Centre
  • Tallinn, Estonia
    • 23301 Innomedica OÜ - Outpatient
  • Tallinn, Estonia
    • 23303 Al Mare Perearstikeskus OÜ
  • Tallinn, Estonia
    • 23304 Merelahe Family Doctors Centre
  • Tallinn, Estonia
    • 23306 Center for Clinical and Basic Research
  • Tartu, Estonia
    • 23305 Clinical Research Center - Vaccine Trials
• Germany
  • Berlin, Germany
    • 27602 Klinische Forschung Berlin
  • Berlin, Germany
    • 27603 Emovis GmbH
  • Dresden, Germany
    • 27608 Klinische Forschung Dresden GmbH
  • Frankfurt, Germany
    • 27609 IKF Pneumologie GmbH & Co. KG
  • Fulda, Germany
    • 27611 Siteworks GmbH
  • Hamburg, Germany
    • 27601 Klinische Forschung Hamburg GmbH
  • Hamburg, Germany
    • 27605 Clinical Research Hamburg GmbH
  • Hannover, Germany
    • 27604 Klinische Forschung Hannover-Mitte GmbH
  • Hannover, Germany
    • 27607 Siteworks GmbH
  • Leipzig, Germany
    • 27606 SIBAmed GmbH & Co KG
  • Stuttgart, Germany
    • 27610 Studienzentrum Leitz Triderm
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • 84013 Coastal Clinical Research, Inc.
  • Arizona
    • Tempe, Arizona, United States, 85281
      • 84007 Alliance for Multispecialty Research
  • Florida
    • Atlantis, Florida, United States, 33462
      • 84005 JEM Research Institute
    • Orlando, Florida, United States, 32819
      • 84010 Headlands Research Orlando
  • Georgia
    • Savannah, Georgia, United States, 31406
      • 84001 Meridian Clinical Research
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • 84003 Meridian Clinical Research
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • 84006 Alliance for Multispecialty Research
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • 84009 Meridian Clinical Research
    • Norfolk, Nebraska, United States, 68701
      • 84002 Meridian Clinical Research
    • Omaha, Nebraska, United States, 68134
      • 84004 Meridian Clinical Research
  • New York
    • Binghamton, New York, United States, 13901
      • 84008 United Medical Associates
    • Endwell, New York, United States, 13760
      • 84011 Meridian Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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:

  1. Clinical conditions
  2. 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
  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: aQIV; Adjuvanted QIV containing 2 influenza type A strains and 2 influenza type B strains	Biological: aQIV; Participants receive a 0.5-mL intramuscular dose of aQIV on Day 1; Other Names: Fluad Tetra/Quadrivalent
Active Comparator: Comparator QIV; Non-adjuvanted comparator QIV containing 2 influenza type A strains and 2 influenza type B strains	Biological: Comparator QIV; Participants receive a 0.5-mL intramuscular dose of Comparator QIV on Day 1; Other Names: Fluarix Tetra/Quadrivalent

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 by Age (Subgroup Analysis)	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: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Influenza Vaccination History (Subgroup Analysis)	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: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Comorbidity Risk Score (Subgroup Analysis)	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

Collaborators and Investigators

• Sponsor: Seqirus
• Investigators: Study Director: Clinical Program Director, Seqirus

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): January 18, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: September 6, 2021
• First Submitted That Met QC Criteria: September 6, 2021
• First Posted (Actual): September 14, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Influenza, Vaccine, MF59 adjuvant
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: V118_23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

SEQIRUS supports the release of anonymized subject-level and study-level data in compliance with regulatory requirements, including Clinical Documents which are part of the CTD modules submitted to regulatory agencies for public release.

Summary results disclosure is either in document form (e.g., ICH E3 Clinical Study Report synopsis) or structured data form (such as summary results in ClinicalTrials.gov (United States) or eudract.ema.europa.eu (EU Clinical Trial Registry [EU CTR])).

• IPD Sharing Time Frame: SEQIRUS discloses results from clinical studies within 12 months of last patient last visit (LPLV) unless otherwise mandated by local laws or regulations.
• IPD Sharing Access Criteria: SEQIRUS will consider requests from qualified scientific and medical researchers to disclose protocols, anonymized subject-level data and study-level data when there is medical, scientific and/or public health interest to ensure the safe use of a Seqirus product licensed on or after 1 January 2014 in the United States (US) and/or the European Union (EU). This applies to Seqirus-sponsored interventional studies initiated after 27 September 2007 and ongoing as of 26 December 2007, that have been included as part of a US or EU submission package which received approval in US and EU on or after 1 January 2014 and have been accepted for publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No