Study to Evaluate Immunogenicity, Safety and Tolerability of Adjuvanted and Non-Adjuvanted H2N3 Influenza Vaccines in Adults

NCT05875961 | Completed Phase 1 FDA Drug

• 1 other identifier: V204_01
• Study Type: interventional
• Target: 600
• Locations: 2 countries
• Sites: 7

Brief Summary

This Phase 1, randomized, observer-blind, dose-ranging clinical study is evaluating 6 different formulations of MF59-adjuvanted and non-adjuvanted H2N3 influenza vaccine. Approximately 600 healthy adult subjects are to be randomized into 1 of 6 possible treatment groups with 100 subjects per group, stratified by age group (born after or before 1968). Each subject will receive an influenza vaccine injection on Day 1 and Day 22. Subjects will be followed up for approximately 12 months after the second vaccine injection. The primary immunogenicity analysis is based on the Day 1, Day 8, Day 22, Day 29, and Day 43 serology data. The primary safety analysis is based on solicited local and systemic adverse events (AEs) reported within 10 days after each vaccination, unsolicited AEs reported within 3 weeks after each vaccination, and serious AEs (SAEs), medically attended AEs (MAAEs), AEs leading to withdrawal from the study, and AEs of special interest (AESIs) reported throughout the study.

Conditions

Influenza, Human; Infections; Respiratory Tract Infections; Virus Diseases; Infection Viral

Keywords

Influenza; Vaccine; MF59; Adjuvant; H2N3

Outcome Measures

Primary Outcomes (40)

• Geometric mean titer (GMT) of hemagglutination inhibition (HI) antibodies against homologous H2N3 strain - Day 1

  GMT (HI) prevaccination

  Day 1

• GMT of HI antibodies against homologous H2N3 strain - Day 8

  GMT (HI) 1 week postvaccination 1

  Day 8

• GMT of HI antibodies against homologous H2N3 strain Day 22

  GMT (HI) 3 weeks postvaccination 1

  Day 22

• GMT of HI antibodies against homologous H2N3 strain - Day 29

  GMT (HI) 1 week postvaccination 2

  Day 29

• GMT of HI antibodies against homologous H2N3 strain - Day 43

  GMT (HI) 3 weeks postvaccination 2

  Day 43

• GMT of microneutralization (MN) antibodies against homologous H2N3 strain - Day 1

  GMT (MN) prevaccination

  Day 1

• GMT of MN antibodies against homologous H2N3 strain - Day 8

  GMT (MN) 1 week postvaccination 1

  Day 8

• GMT of MN antibodies against homologous H2N3 strain - Day 22

  GMT (MN) 3 weeks postvaccination 1

  Day 22

• GMT of MN antibodies against homologous H2N3 strain - Day 29

  GMT (MN) 1 week postvaccination 2

  Day 29

• GMT of MN antibodies against homologous H2N3 strain - Day 43

  GMT (MN) 3 weeks postvaccination 2

  Day 43

• Geometric mean fold increase (GMFI) of HI antibodies against homologous H2N3 strain - Day 8

  GMFI (HI) 1 week postvaccination 1 compared to prevaccination

  Day 8

• GMFI of HI antibodies against homologous H2N3 strain - Day 22

  GMFI (HI) 3 weeks postvaccination 1 compared to prevaccination

  Day 22

• GMFI of HI antibodies against homologous H2N3 strain - Day 29

  GMFI (HI) 1 week postvaccination 2 compared to prevaccination

  Day 29

• GMFI of HI antibodies against homologous H2N3 strain - Day 43

  GMFI (HI) 3 weeks postvaccination 2 compared to prevaccination

  Day 43

• GMFI of MN antibodies against homologous H2N3 strain - Day 8

  GMFI (MN) 1 week postvaccination 1 compared to prevaccination

  Day 8

• GMFI of MN antibodies against homologous H2N3 strain - Day 22

  GMFI (MN) 3 weeks postvaccination 1 compared to prevaccination

  Day 22

• GMFI of MN antibodies against homologous H2N3 strain - Day 29

  GMFI (MN) 1 week postvaccination 2 compared to prevaccination

  Day 29

• GMFI of MN antibodies against homologous H2N3 strain - Day 43

  GMFI (MN) 3 weeks postvaccination 2 compared to prevaccination

  Day 43

• Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 1

  % ≥1:40 (HI) prevaccination

  Day 1

• Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 8

  % ≥1:40 (HI) 1 week postvaccination 1

  Day 8

• Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 22

  % ≥1:40 (HI) 3 weeks postvaccination 1

  Day 22

• Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 29

  % ≥1:40 (HI) 1 week postvaccination 2

  Day 29

• Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Day 43

  % ≥1:40 (HI) 3 weeks postvaccination 2

  Day 43

• Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 1

  % ≥1:40 (MN) prevaccination

  Day 1

• Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 8

  % ≥1:40 (MN) 1 week postvaccination 1

  Day 8

• Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 22

  % ≥1:40 (MN) 3 weeks postvaccination 1

  Day 22

• Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 29

  % ≥1:40 (MN) 1 week postvaccination 2

  Day 29

• Percentages of subjects with MN titers ≥1:40 against homologous H2N3 strain - Day 43

  % ≥1:40 (MN) 3 weeks postvaccination 2

  Day 43

• Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 8

  % seroconversion (HI) 1 week postvaccination 1, defined as a ≥4-fold increase in HI titer postvaccination in those with prevaccination titer ≥1:10, or a postvaccination HI titer ≥1:40 for subjects with baseline titer \<1:10

  Day 8

• Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 22

  % seroconversion (HI) 3 weeks postvaccination 1, defined as a ≥4-fold increase in HI titer postvaccination in those with prevaccination titer ≥1:10, or a postvaccination HI titer ≥1:40 for subjects with baseline titer \<1:10

  Day 22

• Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 29

  % seroconversion (HI) 1 week postvaccination 2, defined as a ≥4-fold increase in HI titer postvaccination in those with prevaccination titer ≥1:10, or a postvaccination HI titer ≥1:40 for subjects with baseline titer \<1:10

  Day 29

• Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Day 43

  % seroconversion (HI) 3 weeks postvaccination 2, defined as a ≥4-fold increase in HI titer postvaccination in those with prevaccination titer ≥1:10, or a postvaccination HI titer ≥1:40 for subjects with baseline titer \<1:10

  Day 43

• Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 8

  % seroconversion (MN) 1 week postvaccination 1, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥lower limit of quantification (LLOQ), or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer \<LLOQ

  Day 8

• Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 22

  % seroconversion (MN) 3 weeks postvaccination 1, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥lower limit of quantification (LLOQ), or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer \<LLOQ

  Day 22

• Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 29

  % seroconversion (MN) 1 week postvaccination 2, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥lower limit of quantification (LLOQ), or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer \<LLOQ

  Day 29

• Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Day 43

  % seroconversion (MN) 3 weeks postvaccination 2, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥lower limit of quantification (LLOQ), or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer \<LLOQ

  Day 43

• Number and percentages of subjects reporting solicited local and systemic adverse events (AEs) - Day 1 through Day 10

  10 consecutive days postvaccination 1

  Day 1 through Day 10

• Number and percentages of subjects reporting solicited local and systemic AEs - Day 22 through Day 31

  10 consecutive days postvaccination 2

  Day 22 through Day 31

• Number and percentage of subjects reporting any unsolicited AEs

  For 3 weeks following each vaccination

  Day 1 through Day 43

• Number and percentage of subjects reporting 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 387

Secondary Outcomes (14)

• GMT of ELLA titers as a measure of anti-neuraminidase (NA) immunogenicity

  Day 1, Day 8, Day 22, Day 29, Day 43

• GMFI of ELLA titers as a measure of anti-NA immunogenicity

  Day 8, Day 22, Day 29, Day 43

• Percentage of subjects with ≥4-fold increase in ELLA titer as a measure of anti-NA immunogenicity

  Day 8, Day 22, Day 29, Day 43

• GMT of HI antibodies against homologous H2N3 strain - Persistence

  Day 202, Day 387

• GMT of MN antibodies against homologous H2N3 strain - Persistence

  Day 202, Day 387

Study Arms (6)

Group A

EXPERIMENTAL

Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of low dose A/H2N3c + standard dose MF59 adjuvant

Biological: Low dose A/H2N3c + standard dose MF59

Group B

EXPERIMENTAL

Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of intermediate dose A/H2N3c + standard dose MF59 adjuvant

Biological: Intermediate dose A/H2N3c + standard dose MF59

Group C

EXPERIMENTAL

Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of high dose A/H2N3c + standard dose MF59 adjuvant

Biological: High dose A/H2N3c + standard dose MF59

Group D

EXPERIMENTAL

Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of high dose A/H2N3c non-adjuvanted

Biological: High dose A/H2N3c non-adjuvanted

Group E

EXPERIMENTAL

Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of lowest dose A/H2N3c + high dose MF59 adjuvant

Biological: Lowest dose A/H2N3c + high dose MF59

Group F

EXPERIMENTAL

Eligible subjects who have been randomized to receive two intramuscular vaccinations (3 weeks apart) of low dose A/H2N3c + high dose MF59 adjuvant

Biological: Low dose A/H2N3c + high dose MF59

Interventions

Low dose A/H2N3c + standard dose MF59 BIOLOGICAL

Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine

Group A

Intermediate dose A/H2N3c + standard dose MF59 BIOLOGICAL

Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine

Group B

High dose A/H2N3c + standard dose MF59 BIOLOGICAL

Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine

Group C

High dose A/H2N3c non-adjuvanted BIOLOGICAL

Two intramuscular injections (3 weeks apart) of cell culture-derived non-adjuvanted H2N3 vaccine

Group D

Lowest dose A/H2N3c + high dose MF59 BIOLOGICAL

Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine

Group E

Low dose A/H2N3c + high dose MF59 BIOLOGICAL

Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine

Group F

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals of 18 years of age and older on the day of informed consent who were not born in 1968.
• Individuals who have voluntarily given written informed 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 last study vaccination.

You may not qualify if:

• 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 last study vaccination.
• A body mass index (BMI) ≥35 kg/m2.
• Progressive, unstable, or uncontrolled clinical conditions as per investigator's assessment. Subjects must be stable and unchanged for a minimum of 3 months.
• 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 resulting from:
• Clinical conditions.
• Systemic administration of corticosteroids at a dose of ≥20 mg/day of prednisone or equivalent 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 are also permitted.
• Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent.
• 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.
• Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
• Study personnel or immediate family or household member of study personnel.
• 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.
• Individuals who received any other vaccines (with the exception of COVID-19 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.

Sponsors & Collaborators

• Seqirus: lead
• Biomedical Advanced Research and Development Authority: collaborator

Study Sites (7)

Meridian Clinical Research

Rockville, Maryland, 20854, United States

Location

Meridian Clinical Research

Lincoln, Nebraska, 68510, United States

Location

Meridian Clinical Research

Omaha, Nebraska, 58134, United States

Location

West Visayas State University Medical Center

Iloilo City, Philippines

Location

Manila Doctors Hospital

Manila, Philippines

Location

Quirino Memorial Medical Center

Quezon City, Philippines

Location

Silang Specialists Medical Center

Silang, Philippines

Location

MeSH Terms

Conditions

Influenza, Human; Infections; Respiratory Tract Infections; Virus Diseases

Interventions

MF59 oil emulsion

Condition Hierarchy (Ancestors)

Orthomyxoviridae Infections; RNA Virus Infections; Respiratory Tract Diseases

Study Officials

• Clinical Science and Strategy

  Seqirus

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible subjects are randomized in an equal ratio to one of the 6 different treatment groups (formulations) and will receive two doses of the allocated H2N3c vaccine (adjuvanted or non-adjuvanted) at 3 weeks apart, ie, at Day 1 and Day 22.

Study Record Dates

• First Submitted: May 5, 2023
• First Posted: May 25, 2023
• Study Start: June 15, 2023
• Primary Completion: November 15, 2024
• Study Completion: November 15, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Locations

US (3); PH (4)