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

A Phase 1, Randomized, Observer-Blind, Multi-Center, Dose Ranging Study to Evaluate the Immunogenicity, Safety and Tolerability of Different Formulations of an Adjuvanted or Non-Adjuvanted Cell Culture-derived A/H2N3 Subunit Influenza Virus Vaccine in Healthy Subjects 18 Years and Above

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.

Study Overview

• Status: Recruiting
• Conditions: Infections; Virus Diseases; Respiratory Tract Infections; Influenza, Human; Infection Viral
• Intervention / Treatment: Biological: Low dose A/H2N3c + standard dose MF59; Biological: Intermediate dose A/H2N3c + standard dose MF59; Biological: High dose A/H2N3c + standard dose MF59; Biological: High dose A/H2N3c non-adjuvanted; Biological: Lowest dose A/H2N3c + high dose MF59; Biological: Low dose A/H2N3c + high dose MF59

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure Manager; Phone Number: use email; Email: seqirus.clinicaltrials@seqirus.com
• Study Contact Backup: Name: Medical Writing & Disclosures

Study Locations

• Philippines
  • Iloilo City, Philippines
    • Recruiting
    • West Visayas State University Medical Center
  • Manila, Philippines
    • Recruiting
    • Manila Doctors Hospital
  • Quezon City, Philippines
    • Recruiting
    • Quirino Memorial Medical Center
  • Silang, Philippines
    • Recruiting
    • Silang Specialists Medical Center
  • Cavite
    • Dasmariñas, Cavite, Philippines, 4114
      • Withdrawn
      • De La Salle Medical and Health Sciences Institute
• United States
  • Maryland
    • Rockville, Maryland, United States, 20854
      • Active, not recruiting
      • Meridian Clinical Research
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Active, not recruiting
      • Meridian Clinical Research
    • Omaha, Nebraska, United States, 58134
      • Active, not recruiting
      • Meridian Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

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 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:

  1. Clinical conditions.
  2. 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.
  3. 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.
• 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 14 days from study vaccination.
• 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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; 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; Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine
Experimental: Group B; 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; Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine
Experimental: Group C; 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; Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine
Experimental: Group D; 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; Two intramuscular injections (3 weeks apart) of cell culture-derived non-adjuvanted H2N3 vaccine
Experimental: Group E; 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; Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine
Experimental: Group F; 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; Two intramuscular injections (3 weeks apart) of cell culture-derived MF59 adjuvanted H2N3 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMT of ELLA titers as a measure of anti-neuraminidase (NA) immunogenicity	GMT (ELLA) prevaccination, 1 and 3 weeks postvaccination	Day 1, Day 8, Day 22, Day 29, Day 43
GMFI of ELLA titers as a measure of anti-NA immunogenicity	GMFI (ELLA) 1 and 3 weeks postvaccination compared to prevaccination	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	% ≥4-fold increase (ELLA) 1 and 3 weeks postvaccination compared to prevaccination	Day 8, Day 22, Day 29, Day 43
GMT of HI antibodies against homologous H2N3 strain - Persistence	GMT (HI) 6 and 12 months postvaccination 2	Day 202, Day 387
GMT of MN antibodies against homologous H2N3 strain - Persistence	GMT (MN) 6 and 12 months postvaccination 2	Day 202, Day 387
GMT of ELLA titer as a measure of anti-NA immunogenicity- Persistence	GMT (ELLA) 6 and 12 months postvaccination 2	Day 202, Day 387
GMFI of HI antibodies against homologous H2N3 strain - Persistence	GMFI (HI) 6 and 12 months postvaccination 2 compared to prevaccination	Day 202, Day 387
GMFI of MN antibodies against homologous H2N3 strain - Persistence	GMFI (MN) 6 and 12 months postvaccination 2 compared to prevaccination	Day 202, Day 387
GMFI of ELLA titer as a measure of anti-NA immunogenicity- Persistence	GMFI (ELLA) 6 and 12 months postvaccination 2 compared to prevaccination	Day 202, Day 387
Percentages of subjects with HI titers ≥1:40 against homologous H2N3 strain - Persistence	% ≥1:40 (HI) 6 and 12 months postvaccination 2	Day 202, Day 387
Percentages of subjects with MN titers ≥1:40, ≥1:80 and ≥1:160 against homologous H2N3 strain - Persistence	% ≥1:40, ≥1:80 and ≥1:160 (MN) 6 and 12 months postvaccination 2	Day 202, Day 387
Percentages of subjects with seroconversion by HI against homologous H2N3 strain - Persistence	% seroconversion (HI) 6 and 12 months 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 202, Day 387
Percentages of subjects with seroconversion by MN against homologous H2N3 strain - Persistence	% seroconversion (MN) 6 and 12 months postvaccination 2, defined as a ≥4-fold increase in MN titer postvaccination in those with prevaccination titer ≥LLOQ, or a postvaccination MN titer ≥4×LLOQ for subjects with baseline titer <LLOQ	Day 202, Day 387
Percentage of subjects with ≥4-fold increase in ELLA titer as a measure of anti-NA immunogenicity - Persistence	% ≥4-fold increase (ELLA) 6 and 12 months postvaccination 2 compared to prevaccination	Day 202, Day 387

Collaborators and Investigators

• Sponsor: Seqirus
• Collaborators: Department of Health and Human Services
• Investigators: Study Chair: Clinical Science & Strategy, Seqirus

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: May 16, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Influenza; Vaccine; Adjuvant; MF59; H2N3
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Respiratory Tract Diseases; Disease Attributes; Orthomyxoviridae Infections; Infections; Communicable Diseases; Virus Diseases; Influenza, Human; Respiratory Tract Infections; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; MF59 oil emulsion
• Other Study ID Numbers: V204_01

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