A Study to Evaluate Safety and Immunogenicity of One or Two Booster Vaccinations With H5N6 Influenza Vaccine in Adults Primed With H5N1 Influenza Vaccine or Unprimed

A Phase 2, Randomized, Study to Evaluate Safety and Immunogenicity of One or Two Heterologous Booster Vaccinations With an MF59-adjuvanted, Cell Culture-derived H5N6 Influenza Vaccine in Adults Primed With MF59-adjuvanted, Cell Culture-derived H5N1 Influenza Vaccine or Unprimed

This is a Phase 2, randomized, multi-center study in approximately 300 adults who received 2 doses of aH5N1c or placebo in and completed the parent study V89_18 in the <65 years of age cohort. The study investigates whether two priming doses of MF59-adjuvanted H5N1 cell culture-derived vaccine (aH5N1c) followed by one or two booster vaccinations with a MF59-adjuvanted H5N6 cell culture derived vaccine (aH5N6c) 3 weeks apart elicit immune responses to the antigens used for priming (H5N1) and boosting (H5N6) after first and second heterologous booster vaccination.

Eligible subjects, who received 2 doses of aH5N1c in the parent study V89_18 are randomized in a 1:1 ratio to receive either two aH5N6c vaccinations, 3 weeks apart (group 1) or an aH5N6c vaccination on Day 1 and saline placebo on Day 22 (group 2). Eligible subjects, who received placebo in the parent study will receive two aH5N6c vaccinations, 3 weeks apart (group 3). After the second vaccine administration, subjects are monitored for approximately 6 months for safety and antibody persistence. The total study duration will be approximately 7 months per subject.

Study Overview

• Status: Completed
• Conditions: Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Influenza, Human; Orthomyxoviridae Infections; Influenza in Birds
• Intervention / Treatment: Biological: aH5N6c on Day 1; Biological: aH5N6c on Day 22; Biological: Placebo on Day 22

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
      • Optimal Research, LLC
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Research Consortium Arizona
  • California
    • San Diego, California, United States, 92103
      • California Research Foundation
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting, LLC
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Melbourne, Florida, United States, 32934
      • Optimal Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials LLC
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research
    • St Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh
    • Winston-Salem, North Carolina, United States, 27103
      • Accellacare
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research
  • Texas
    • San Antonio, Texas, United States, 78229
      • Biogenics Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc/Foothill Family Clinic North
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc/Foothill Family Clinic South
    • South Jordan, Utah, United States, 84095
      • J. Lewis Research, Inc/Jordan River Family Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects who received 2 doses of aH5N1c vaccine or placebo in and completed the parent study V89_18 in the <65 years of age cohort.
• Individuals who can comply with study procedures including follow-up.

Exclusion Criteria:

• 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 at least 30 days after the last 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.
• Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
• Abnormal function of the immune system.
• History of any medical condition considered an adverse event of special interest (AESI).
• Received immunoglobulins with immunomodulating effects or any blood products within 180 days prior to informed consent.
• Subjects, who received an influenza H5 vaccine other than in the V89_18 parent study or have a history of H5 influenza infection prior to enrollment.
• Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
• Individuals who received any other vaccines [except corona virus disease 2019 (COVID-19) vaccines] within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who are planning to receive any vaccine within 28 days from the study vaccination.
• Receipt of any COVID-19 vaccine within 7 days prior to enrollment or plan to receive any COVID-19 vaccine within 7 days from study vaccination.
• Acute (severe) febrile illness.
• A known history of Guillain-Barre Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Eligible subjects who received 2 doses of aH5N1c in the parent study V89_18 and have been randomized to receive two aH5N6c vaccinations, 3 weeks apart	Biological: aH5N6c on Day 1; MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 hemagglutinin (HA) (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume); Biological: aH5N6c on Day 22; MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 HA (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume) given 3 weeks after the first aH5N6c vaccination
Experimental: Group 2; Eligible subjects who received 2 doses of aH5N1c in the parent study V89_18 and have been randomized to receive an aH5N6c vaccination on Day 1 and saline placebo on Day 22	Biological: aH5N6c on Day 1; MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 hemagglutinin (HA) (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume); Biological: Placebo on Day 22; Saline placebo (sterile, 0.5 mL) given 3 weeks after the aH5N6c vaccination
Experimental: Group 3; Eligible subjects who received placebo in the parent study V89_18 receive two aH5N6c vaccinations, 3 weeks apart.	Biological: aH5N6c on Day 1; MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 hemagglutinin (HA) (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume); Biological: aH5N6c on Day 22; MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular (IM) administration, containing 7.5 μg H5N6 HA (A/Guangdong/18SF020/2018 (H5N6)-like) + 0.25 mL MF59 (approximately 0.5 mL total volume) given 3 weeks after the first aH5N6c vaccination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HI) Antibodies Against the H5N6 Strain	GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the per-protocol set (PPS); definitions are provided in the Statistical Analysis Plan (SAP). The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.	Day 1, Day 8, Day 22, Day 43
Geometric Mean Fold Increase (GMFI) of HI Antibodies Against the H5N6 Strain	GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 compared to pre-vaccination (Day 1) Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.	Day 1, Day 8, Day 22, Day 43
Percentage of Subjects With HI Titers ≥1:40 Against the H5N6 Strain	Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.	Day 1, Day 8, Day 22, Day 43
Percentage of Subjects With Seroconversion Against the H5N6 Strain	Seroconversion 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer <1:10 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.	Day 8, Day 22, Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMT of HI Antibodies Against the H5N1 Strain	GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.	Day 1, Day 8, Day 22, Day 43, Day 202
GMFI of HI Antibodies Against the H5N1 Strain	GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 compared to pre-vaccination (Day 1) Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.	Day 1, Day 8, Day 22, Day 43, Day 202
Percentage of Subjects With HI Titers ≥1:40 Against the H5N1 Strain	Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.	Day 1, Day 8, Day 22, Day 43, Day 202
Percentage of Subjects With Seroconversion Against the H5N1 Strain	Seroconversion 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer <1:10 Note: The Overall Number of Participants Analyzed (N) represents the total number of participants in the PPS; definitions are provided in the SAP. The Number Analyzed (n) at each timepoint corresponds to the number of participants with an available serum analysis result for the relevant strain at that timepoint. Instances where n<N reflect missing serum samples or non-evaluable results. All participants included in the Overall Number of Participants Analyzed contributed data to the analysis at one or more timepoints.	Day 8, Day 22, Day 43, Day 202
GMT of HI Antibodies Against the H5N6 Strain	GMT 6 months post-vaccination 2	Day 202
GMFI of HI Antibodies Against the H5N6 Strain	GMFI 6 months post-vaccination 2 compared to pre-vaccination (Day 1)	Day 1, Day 202
Percentage of Subjects With HI Titers ≥1:40 Against the H5N6 Strain	6 months post-vaccination 2	Day 202
Percentage of Subjects With Seroconversion Against the H5N6 Strain	Seroconversion 6 months post-vaccination 2, defined as a ≥4-fold increase in HI titer post-vaccination in those with pre-vaccination titer ≥1:10, or a post-vaccination HI titer ≥1:40 for subjects with baseline titer <1:10	Day 202
Frequency and Severity of Solicited Local and Systemic Adverse Events (AEs)	For 7 days following each vaccination	Day 1 through Day 7 and Day 22 through Day 28
Frequency and Severity of Unsolicited AEs	For 3 weeks following each vaccination	Day 1 through Day 43
Frequency of Serious AEs (SAEs), AEs Leading to Withdrawal, AEs of Special Interest (AESI) and Medically Attended AEs (MAAEs)	From vaccination until study completion	Day 1 through Day 202

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2022
• Primary Completion (Actual): October 24, 2022
• Study Completion (Actual): March 24, 2023

Study Registration Dates

• First Submitted: June 14, 2022
• First Submitted That Met QC Criteria: June 14, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Influenza; Vaccine; H5N1; Flu; Pandemic; MF59; H5N6; Avian
• Additional Relevant MeSH Terms: Animal Diseases; Bird Diseases; Influenza, Human; Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Influenza in Birds; RNA Virus Infections; Orthomyxoviridae Infections
• Other Study ID Numbers: V89_18E1

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No