Safety and Immunogenicity of Different Formulations of an MF59-Adjuvanted Influenza Vaccine in Older Adults ≥50 Years of Age

A Phase 2b, Randomized, Observer-Blind, Antigen and Adjuvant Dose-Confirmation Clinical Study to Evaluate Safety and Immunogenicity of Different Formulations of MF59-Adjuvanted Quadrivalent Subunit Inactivated Cell-derived Influenza Vaccine (aQIVc) in Older Adults ≥50 Years of Age

This Phase 2, randomized, observer-blind, dose-confirmation clinical study evaluated different formulations of MF59-Adjuvanted Quadrivalent Subunit Inactivated Influenza Vaccine. Approximately 1000 subjects were randomized into 1 of 4 possible treatment groups with approximately 250 participants per group. Every participant received an influenza vaccine injection on Day 1 and were to be followed up for approximately 6 months following injection. The primary immunogenicity analysis is based on Day 29 serology data.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: Experimental: IIV-A Investigational IIV-A administered as a single dose intramuscularly on Day 1; Biological: Experimental: aIIV-B Investigational aIIV-B administered as a single dose intramuscularly on Day 1; Biological: Experimental: aIIV-C Investigational aIIV-C administered as a single dose intramuscularly on Day 1; Biological: Active Comparator: Licensed IIV IIV administered as a single dose intramuscularly on Day 1

• Study Type: Interventional
• Enrollment (Actual): 1056
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85281
      • AMR Tempe
  • California
    • Huntington Beach, California, United States, 92647
      • Marvel Clinical Research
    • San Diego, California, United States, 92123
      • California Research Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80920
      • The Lynn Institute of The Rockies
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting, LLC
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Edgewater, Florida, United States, 32132
      • Velocity Clinical Research - New Smyrna Beach
    • Hollywood, Florida, United States, 33024
      • CenExel RCA
    • Jupiter, Florida, United States, 33458
      • Health Awareness INC
    • Miami Lakes, Florida, United States, 33016
      • Global Health Research Center
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research
    • Tampa, Florida, United States, 33615
      • Global Health Research Center
  • Georgia
    • Savannah, Georgia, United States, 31405
      • Platinum Research Network, LLC
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research - Savannah
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • AMR El Dorado
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • AMR Lexington
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Meridian Clinical Research
    • Metairie, Louisiana, United States, 70006
      • Medpharmics, LLC
  • Maryland
    • Rockville, Maryland, United States, 20854
      • Rockville Internal Medicine Group
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • MedPharmics LLC
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Healthcare Research Network
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research
    • St Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Meridian Clinical Research
    • Grand Island, Nebraska, United States, 68803
      • Meridian Clinical Research
    • Lincoln, Nebraska, United States, 68510
      • Meridian Clinical Research, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Alliance for Multispecialty Research, LLC, Las Vegas
  • New York
    • Binghamton, New York, United States, 13901
      • Meridian Clinical Research (Binghamton, NY)
    • Endwell, New York, United States, 13760
      • Meridian Clinical Research, LLC
    • Syracuse, New York, United States, 13057
      • Velocity Clinical Research - Syracuse
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • Meridian Clinical Research, LLC
    • Cincinnati, Ohio, United States, 45219
      • Meridian Clinical Research, LLC
    • Columbus, Ohio, United States, 43213
      • Aventiv Research, Inc. Columbus
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Oregon
    • Medford, Oregon, United States, 97504
      • Velocity Clinical Research - Medford
  • South Carolina
    • Gaffney, South Carolina, United States, 29340
      • Velocity Clinical Research, Gaffney
    • Greenville, South Carolina, United States, 29615
      • Velocity Clinical Research - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • Velocity Clinical Research, Spartanburg
  • South Dakota
    • Dakota Dunes, South Dakota, United States, 57049
      • Meridian Clinical Research - Dakota Dunes
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • AMR Coastal Clinical Research
  • Texas
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • JBR Clinical Research
    • West Jordan, Utah, United States, 84088
      • Velocity Clinical Research - West Jordan
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • CVS pharmacy - Charlottesville
    • Reston, Virginia, United States, 20190
      • CVS pharmacy - Reston
    • Richmond, Virginia, United States, 23235
      • CVS pharmacy - Richmond

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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

1. Individuals ≥50 years of age on the day of informed consent.
2. 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.
3. Individuals who can comply with study procedures including follow-up .

4. 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:

1. 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 informed consent and who do not plan to do so for at least 2 months after the study vaccination.
2. Progressive, unstable or uncontrolled clinical conditions.
3. Hypersensitivity, including allergy, to any component of vaccines whose use is foreseen in this study.
4. History of any medical condition considered an adverse event of special interest (AESI).
5. Known history of Guillain-Barré syndrome or another demyelinating disease such as encephalomyelitis and transverse myelitis.
6. Clinical conditions representing a contraindication 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 of ≥20 mg/day of prednisone or equivalent for more than 14 consecutive days within 90 days prior to informed consent5.
   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 an investigational or non-registered medicinal product within 30 days prior to informed consent.
10. Receipt of any COVID-19 vaccine within 14 days (non-replicating vaccines) or 28 days (replicating vaccines) prior to informed consent or plan to receive any COVID-19 vaccine within 7 days from study vaccination
11. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to informed consent or who are planning to receive any vaccine within 28 days from the study vaccines.
12. Study personnel or immediate family or household member of study personnel.
13. Receipt of any influenza vaccine within 6 months prior to informed consent, or plan to receive an influenza vaccine during the study period.
14. Acute (severe) febrile illness,

15. 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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IIV-A Investigational	Biological: Experimental: IIV-A Investigational IIV-A administered as a single dose intramuscularly on Day 1; Biological/Vaccine: Investigational IIV-A Investigational Quadrivalent Influenza vaccine (higher hemagglutinin [HA] dose), containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
Experimental: aIIV-B Investigational	Biological: Experimental: aIIV-B Investigational aIIV-B administered as a single dose intramuscularly on Day 1; Biological/Vaccine: Investigational aIIV-B Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine (higher HA dose, standard dose MF59), containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
Experimental: aIIV-C Investigational	Biological: Experimental: aIIV-C Investigational aIIV-C administered as a single dose intramuscularly on Day 1; Biological/Vaccine: Investigational aIIV-C Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine (higher HA dose, higher dose MF59), containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.
Active Comparator: Licensed IIV	Biological: Active Comparator: Licensed IIV IIV administered as a single dose intramuscularly on Day 1; Biological/Vaccine: Licensed IIV Licensed Non-adjuvanted Quadrivalent Influenza vaccine (standard HA dose), containing four influenza virus strains (A/H1N1, A/H3N2, B/Yamagata and Victoria lineage) recommended by the WHO (World Health Organization) for quadrivalent vaccines for the respective season.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Endpoint: Geometric Mean Titer (GMT): Geometric Mean of Hemagglutination Inhibition (HI) Antibodies at Day 1 and Day 29	GMTs on Day 1 (prior to vaccination) and Day 29 as determined by HI assay against each of the 4 vaccine strains. No hypothesis testing was performed for the primary immunogenicity objectives.	Day 1 and Day 29
Immunogenicity Endpoint: Geometric Mean Fold Increase (GMFI) (HI Assay)	Geometric mean of the fold increase in serum HI titer postvaccination (Day 29) compared to prevaccination (Day 1) for each of the 4 vaccine strains.	Day 1 to Day 29
Immunogenicity Endpoint: Percentages of Subjects With HI Titers ≥1:40 at Day 1 and Day 29	Percentages of subjects with HI titers ≥1:40 at Day 1 and Day 29 for each of the 4 vaccine strains.	Day 1 and Day 29
Immunogenicity Endpoint: Percentage of Subjects With Seroconversion at Day 29 (HI Assay)	Seroconversion is defined as ≥4-fold increase in titer postvaccination in those with prevaccination titer equal to or above the lower limit of quantitation (LLOQ; 1:10), or a postvaccination titer ≥1:40 for subjects with baseline titer below the LLOQ (1:10) for HI antibodies.	Day 1 to Day 29
Immunogenicity Endpoint: GMT Ratio (HI Assay)	The GMT ratio is the geometric mean of the postvaccination HI titer for the investigational vaccine over the geometric mean of the postvaccination HI titer for the licensed IIV vaccine. The Day 29 GMT ratios are calculated for the investigational vaccines with reference to the licensed vaccine, ie, the Day 29 GMT ratios are the ratio of the Day 29 GMTs in the Investigational group (IIV-A Investigational, aIIV-B Investigational, or aIIV-C Investigational) compared with the Day 29 GMTs in the Licensed IIV group (ie, Investigational group/Licensed IIV group). As the licensed vaccine is the reference for the GMT ratio, this parameter is presented as "1" for the Licensed IIV group (ie, Licensed IIV group/Licensed IIV group).	Day 29
Solicited Local or Systemic AEs	Number and percentage of subjects with solicited local or systemic AEs for 7 days following vaccination, based on the subject reported data (electronic Diary [eDiary]). No hypothesis testing was performed for the primary safety objectives.	Day 1 through Day 7
Severe Solicited Local or Systemic AEs	Number and percentage of subjects with severe solicited local or systemic AEs for 7 days following vaccination, based on the subject reported data (eDiary).	Day 1 through Day 7
Unsolicited AEs	Number and percentage of subjects with unsolicited AEs for 28 days following vaccination	Day 1 to Day 29
Subjects With Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESIs) and Medically-attended Adverse Events (MAAEs)	Number and percentage of subjects with SAEs, AEs leading to withdrawal from the study, AESIs and non-serious MAAEs	Day 1 to Day 181

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Endpoint: GMT: Geometric Mean of Microneutralization (MN) Antibodies Titer at Days 1 and 29	GMTs on Day 1 (prior to vaccination) and Day 29 as determined by MN assay against each of the 4 vaccine strains.	Day 1 and Day 29
Immunogenicity Endpoint: GMFI (MN Assay)	Geometric mean of the fold increase in serum MN titer postvaccination (Day 29) compared to prevaccination (Day 1) for each of the 4 vaccine strains.	Day 1 to Day 29
Immunogenicity Endpoint: Percentages of Subjects With Seroconversion at Day 29 (MN Assay)	Seroconversion is defined as ≥4-fold increase for subjects with prevaccination MN titers ≥LLOQ (1:10) or as ≥4*LLOQ (1:10) for subjects with prevaccination MN titer <LLOQ.	Day 1 to Day 29
Immunogenicity Endpoint: GMT Ratio (MN Assay)	The GMT ratio is the geometric mean of the postvaccination HI titer for the investigational vaccine over the geometric mean of the postvaccination HI titer for the licensed IIV vaccine. The Day 29 GMT ratios are calculated for the investigational vaccines with reference to the licensed vaccine, ie, the Day 29 GMT ratios are the ratio of the Day 29 GMTs in the Investigational group (IIV-A Investigational, aIIV-B Investigational, or aIIV-C Investigational) compared with the Day 29 GMTs in the Licensed IIV group (ie, Investigational group/Licensed IIV group). As the licensed vaccine is the reference for the GMT ratio, this parameter is presented as "1" for the Licensed IIV group (ie, Licensed IIV group/Licensed IIV group).	Day 29

Collaborators and Investigators

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

Publications and helpful links

General Publications

• de Looze F, Essink BJ, van Boxmeer J, Andrade C, de Rooij R, Casula D, Xing R, Tovar MP, Albano FR. Immunogenicity and safety of higher-dose cell-based adjuvanted quadrivalent influenza vaccines: Combined results of randomised, controlled dose-finding and dose-confirmation studies. Vaccine. 2026 Apr 19;79:128436. doi: 10.1016/j.vaccine.2026.128436. Epub 2026 Mar 19.

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2022
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: August 11, 2022
• First Submitted That Met QC Criteria: August 11, 2022
• First Posted (Actual): August 15, 2022

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: influenza, vaccine, MF59, adjuvant
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human
• Other Study ID Numbers: V201_07

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 completion of the study 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