Safety and Immunogenicity of Different Formulations of an MF59-Adjuvanted Influenza Vaccine in Older Adults

A Phase 2, Randomized, Observer-blind, Antigen and Adjuvant Dose Ranging 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, antigen and adjuvant dose-ranging Clinical study is evaluating different formulations of MF59-Adjuvanted Quadrivalent Subunit Inactivated Influenza Vaccine. Approximately 800 subjects are to be randomized into 1 of 8 possible treatment groups. Immunogenicity and safety will be assessed in the overall study population (adults ≥50 years and above) and in the age subgroups ≥50-64 years and ≥65 years. Data from this study will be used to select the optimal dose to be tested in the pivotal Phase 3 immunogenicity and safety study in older adults.

Disclosure Statement: This is a parallel-group dose-ranging study with 8 arms that is participant, investigator and observer-blinded.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Drug: aQII-1; Drug: aQII-3 Investigational; Drug: aQII-6 Investigational; Other: aQII-7 Investigational; Drug: aQII-9 Investigational; Drug: aQII-10 Investigational; Drug: aQII-11 Investigational; Drug: Licensed QII Active Comparator

• Study Type: Interventional
• Enrollment (Actual): 839
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Canberra
    • Bruce, Canberra, Australia, 2617
      • 03607 - PCRN_Paratus Clinical Research
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • 03605 - PCRN_Paratus Clinical Research (Central Coast)
    • Botany, New South Wales, Australia, 2019
      • 3610- Emeritis Research
    • Brookvale, New South Wales, Australia, 2100
      • 3609 - Northern Beaches Clinical Research [NSW]
    • Kanwal, New South Wales, Australia, 2259
      • 03602 - PCRN_Paratus Clinical Research,(Western Sydney) [NSW]
    • Maroubra, New South Wales, Australia, 2035
      • 03608 - Australian Clinical Research Network - ACRN [NSW]
  • Queensland
    • Morayfield, Queensland, Australia, 4506
      • 03604 - University of the Sunshine Coast Clinical Trials Centre
    • Sippy Downs, Queensland, Australia, 4556
      • 03603 - University of the Sunshine Coast
    • Taringa, Queensland, Australia, 4068
      • 03601 - AusTrials Taringa [QLD]
    • Tarragindi, Queensland, Australia, 4121
      • 03606 - AusTrials Tarragindi (Aus Trial Wellers Hill)[QLD]
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • 3611 - The University of Melbourne Peter Doherty Institute for Infection and Immunity
• New Zealand
  • Auckland, New Zealand, 1010
    • 55406 - Optimal Clinical Trials
  • Christchurch, New Zealand, 8013
    • 55404- PCRN_Southern Clinical Trials Christchurch
  • Hamilton, New Zealand, 3200
    • 55403-PCRN_Lakeland Clinical Trials Waikato
  • Rotorua, New Zealand, 3010
    • 55405 - PCRN_Lakeland Clinical Trials
  • Auckland
    • Birkenhead, Auckland, New Zealand, 0626
      • 55402- PCRN_Southern Clinical Trials Waitemata
    • New Lynn, Auckland, New Zealand, 0600
      • 55401- PCRN_Southern Clinical Trials Totara
• Philippines
  • Manila, Philippines, 1000
    • 60803 - Philippine General Hospital
  • Cavite
    • Dasmariñas, Cavite, Philippines, 4114
      • 60801 - De La Salle Medical and Health Sciences Institute
  • Iloilo City
    • Jaro, Iloilo City, Philippines, 5000
      • 60802 - West Visayas University Medical Center
  • Manila
    • Ermita, Manila, Philippines, 1000
      • 60805 - Manila Doctors' Hospital
  • Quezon
    • Quezon City, Quezon, Philippines, 1109
      • 60804 - Quirino Memorial Medical Center
• South Africa
  • Bellville, South Africa, 7531
    • 71005 South Africa Haylene71005 - Tiervlei Trial Centre -- Karl Bremer Hospital
  • Bloemfontein, South Africa, 9301
    • 71002 - JOSHA Research
  • Bloemfontein, South Africa, 9301
    • 71011 - Farmovs
  • Cape Town, South Africa, 7505
    • 71004 - Tread Research -- Tygerberg Hospital
  • Mpumalanga, South Africa, 1050
    • 71006 - Mzansi Ethical Research Centre (MERC)
  • Paarl, South Africa, 7626
    • 71009 - Be Part Yoluntu Centre
  • Soweto, South Africa, 2013
    • 71001 - Wits Clinical Researc - Chris Hani Baragwanath Academic Hospital
  • Johannesburg
    • Newtown, Johannesburg, South Africa, 2113
      • 71003- Newtown Clinical Research

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 consent.
   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 vaccination.
10. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine within 28 days from the study vaccines.
11. Study personnel or immediate family or household member of study personnel.
12. Receipt of any influenza vaccine within 6 months prior to vaccination in this study, or plan to receive an influenza vaccine during the study period.
13. Acute (severe) febrile illness.
14. 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: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A aQII-1 Investigational	Drug: aQII-1; Biological/Vaccine: Investigational aQII-1 Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine, 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: Group B aQII-3 Investigational	Drug: aQII-3 Investigational; Biological/Vaccine: Investigational aQII-3 Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine, 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: Group C aQII-6 Investigational	Drug: aQII-6 Investigational; Biological/Vaccine: Investigational aQII-6 Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine, 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: Group D aQII-7 Investigational	Other: aQII-7 Investigational; Biological/Vaccine: Investigational aQII-7 Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine, 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: Group E aQII-9 Investigational	Drug: aQII-9 Investigational; Biological/Vaccine: Investigational aQII-9 Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine, 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: Group F aQII-10 Investigational	Drug: aQII-10 Investigational; Biological/Vaccine: Investigational aQII-10 Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine, 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: Group G aQII-11 Investigational	Drug: aQII-11 Investigational; Biological/Vaccine: Investigational aQII-11 Investigational MF59 Adjuvanted Quadrivalent Influenza vaccine, 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: Group H Licensed QII Active Comparator	Drug: Licensed QII Active Comparator; Biological/Vaccine: Licensed QII Licensed Quadrivalent Influenza vaccine, 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) for the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay and for A/H3N2 Strain Using Microneutralization Assay		[28 days post-vaccination]
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) (GMR is GMT Ratio of aQII Formulation/Licensed QII) for the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by HI Assay and for A/H3N2 Strain Using MN Assay		28 days post-vaccination
Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion for the A/H1N1, B/Victoria and B/Yamagata Strains by HI Assay and A/H3N2 Strain Using MN Assay	Seroconversion is defined as ≥4-fold increase in titer postvaccination in those with pre-vaccination titer above or equal to the Lower Limit of Quantitation (LLOQ) (≥1:10), or a post-vaccination titer ≥1:40 for subjects with baseline titer below the LLOQ (1:10) for HI titers	28 days post-vaccination
Immunogenicity Endpoint: Percentage of Subjects With HI Titer ≥1:40 for A/H1N1, B/Yamagata and B/Victoria Strains (HI Assay)		28 days post-vaccination
Safety Endpoint: Percentage of Subjects With Solicited Local or Systemic Reactions	Percentage of subjects with at least one solicited AE Day 1 through Day 7 after study vaccination	7 days post-vaccination
Safety Endpoint: The Percentage of Subjects With Any Unsolicited Adverse Events	The percentage of subjects with at least one unsolicited AE from Day 1 to Day 29. Related AEs = considered at least possibly related to study vaccination by the investigator	28 days post-vaccination
Safety Endpoint: The Percentage of Subjects With Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESI) and Medically Attended Adverse Events (MAAEs)		28 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Endpoint: The Percentage of Subjects With Serious Adverse Events (SAEs), AEs Leading to Withdrawal, Adverse Events of Special Interest (AESI) and Medically Attended Adverse Events (MAAEs) During the Entire Study Period		180 days post-vaccination
Immunogenicity Endpoint: Geometric Mean Titer (GMT) for the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Microneutralization (MN) Assay		28 days post-vaccination
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) (GMR is GMT Ratio of aQII Formulation/Licensed QII) for the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Microneutralization Assay		28 days post-vaccination
Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion for the A/H1N1, B/Victoria and B/Yamagata Strains by MN Assay	Seroconversion is defined as ≥4-fold increase in titer postvaccination in those with pre-vaccination titer above or equal to the Lower Limit of Quantitation (LLOQ) (≥1:10), or a post-vaccination titer ≥1:40 for subjects with baseline titer below the LLOQ (1:10) for HI titers	28 days post-vaccination
Immunogenicity Endpoint: Geometric Mean Titer (GMT) for the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay		180 days post-vaccination
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) (GMR is GMT Ratio of aQII Formulation/Licensed QII) for the A/H1N1, B/Victoria and B/Yamagata Vaccine Strains by Hemagglutination Inhibition (HI) Assay		180 days post-vaccination
Immunogenicity Endpoint: Percentage of Subjects With HI Titer ≥1:40 for A/H1N1, B/Yamagata and B/Victoria Strains (HI Assay)		180 days post-vaccination
Immunogenicity Endpoint: Geometric Mean Titer (GMT) for the A/H1N1, A/H3N2, B/Victoria and B/Yamagata Vaccine Strains by MN Assay		180 days post-vaccination
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) (GMR is GMT Ratio of aQII Formulation/Licensed QII) for the A/H1N1, A/H3N2, B/Victoria and B/Yamagata Vaccine Strains by MN Assay		180 days post-vaccination

Collaborators and Investigators

• Sponsor: Seqirus
• Investigators: Study Chair: Therapeutic Area Head, Seqirus

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Actual): September 22, 2021
• Study Completion (Actual): March 3, 2022

Study Registration Dates

• First Submitted: March 1, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: V201_01

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

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