Study to Evaluate Safety and Immunogenicity of Different Priming and Booster Regimens With Adjuvanted H5N8 and/or H5N6 Influenza Vaccine in Adults

NCT05874713 | Completed Phase 2 FDA Drug

• 1 other identifier: V205_01
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 9

Brief Summary

This Phase 2, randomized, observer-blind clinical study is evaluating 3 different priming and booster regimens with MF59-adjuvanted H5N8 and/or H5N6 cell culture-derived influenza vaccine (aH5N8c; aH5N6c). Approximately 480 healthy adult subjects are to be randomized into 1 of 3 possible treatment groups, stratified by age group (18-64 years and ≥65 years) and by poultry worker status (yes/no). Each subject will receive a priming influenza vaccine injection on Day 1 and Day 22 and a booster vaccination on Day 202. Subjects will be followed up for approximately 6 months after the booster injection. The primary immunogenicity analysis is based on antibody responses against H5N8 and H5N6 as measured by hemagglutination inhibition (HI) assay on Day 1, Day 22, Day 29, Day 43, Day 202, Day 209 (H5N8 only), and Day 223.

Conditions

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

Keywords

Influenza; Vaccine; MF59; Adjuvant; H5N8; H5N6; Pandemic; Avian

Outcome Measures

Primary Outcomes (34)

• Geometric mean titer (GMT) of hemagglutination inhibition (HI) antibodies against H5N8 strain - Day 1

  GMT (HI) prevaccination

  Day 1

• GMT of HI antibodies against H5N8 strain - Day 22

  GMT (HI) 3 weeks post first priming vaccination

  Day 22

• GMT of HI antibodies against H5N8 strain - Day 43

  GMT (HI) 3 weeks post second priming vaccination

  Day 43

• GMT of HI antibodies against H5N8 strain - Day 202

  GMT (HI) pre booster vaccination

  Day 202

• GMT of HI antibodies against H5N8 strain - Day 209

  GMT (HI) 1 week post booster vaccination

  Day 209

• GMT of HI antibodies against H5N8 strain - Day 223

  GMT (HI) 3 weeks post booster vaccination

  Day 223

• GMT of HI antibodies against H5N6 strain - Day 1

  GMT (HI) prevaccination

  Day 1

• GMT of HI antibodies against H5N6 strain - Day 22

  GMT (HI) 3 weeks post first priming vaccination

  Day 22

• GMT of HI antibodies against H5N6 strain - Day 43

  GMT (HI) 3 weeks post second priming vaccination

  Day 43

• GMT of HI antibodies against H5N6 strain - Day 202

  GMT (HI) pre booster vaccination

  Day 202

• GMT of HI antibodies against H5N6 strain - Day 223

  GMT (HI) 3 weeks post booster vaccination

  Day 223

• Geometric mean fold increase (GMFI) of HI antibodies against H5N8 strain - Day 22

  GMFI (HI) 3 weeks post first priming vaccination compared to prevaccination

  Day 22

• GMFI of HI antibodies against H5N8 strain - Day 43

  GMFI (HI) 3 weeks post second priming vaccination compared to prevaccination

  Day 43

• GMFI of HI antibodies against H5N8 strain - Day 209

  GMFI (HI) 1 week post booster vaccination compared to pre booster vaccination

  Day 209

• GMFI of HI antibodies against H5N8 strain - Day 223

  GMFI (HI) 3 weeks post booster vaccination compared to pre booster vaccination

  Day 223

• GMFI of HI antibodies against H5N6 strain - Day 22

  GMFI (HI) 3 weeks post first priming vaccination compared to prevaccination

  Day 22

• GMFI of HI antibodies against H5N6 strain - Day 43

  GMFI (HI) 3 weeks post second priming vaccination compared to prevaccination

  Day 43

• GMFI of HI antibodies against H5N6 strain - Day 223

  GMFI (HI) 3 weeks post booster vaccination compared to pre booster vaccination

  Day 223

• Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 1

  % ≥1:40 (HI) prevaccination

  Day 1

• Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 22

  % ≥1:40 (HI) 3 weeks post first priming vaccination

  Day 22

• Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 43

  % ≥1:40 (HI) 3 weeks post second priming vaccination

  Day 43

• Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 209

  % ≥1:40 (HI) 1 week post booster vaccination

  Day 209

• Percentages of subjects with HI titers ≥1:40 against H5N8 strain - Day 223

  % ≥1:40 (HI) 3 weeks post booster vaccination

  Day 223

• Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Day 1

  % ≥1:40 (HI) prevaccination

  Day 1

• Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Day 22

  % ≥1:40 (HI) 3 weeks post first priming vaccination

  Day 22

• Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Day 43

  % ≥1:40 (HI) 3 weeks post second priming vaccination

  Day 43

• Percentages of subjects with HI titers ≥1:40 against H5N6 strain - Day 223

  % ≥1:40 (HI) 3 weeks post booster vaccination

  Day 223

• Percentages of subjects with seroconversion by HI against H5N8 strain - Day 22

  % seroconversion (HI) 3 weeks post first priming vaccination, 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 prevaccination titer \<1:10

  Day 22

• Percentages of subjects with seroconversion by HI against H5N8 strain - Day 43

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

  Day 43

• Percentages of subjects with seroconversion by HI against H5N8 strain - Day 209

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

  Day 209

• Percentages of subjects with seroconversion by HI against H5N8 strain - Day 223

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

  Day 223

• Percentages of subjects with seroconversion by HI against H5N6 strain - Day 22

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

  Day 22

• Percentages of subjects with seroconversion by HI against H5N6 strain - Day 43

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

  Day 43

• Percentages of subjects with seroconversion by HI against H5N6 strain - Day 223

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

  Day 223

Secondary Outcomes (19)

• Frequency and severity of solicited local and systemic adverse events (AEs)

  Day 1 through Day 7, Day 22 through Day 28, and Day 202 through 208

• Frequency and severity of unsolicited AEs

  Day 1 through Day 43 and Day 202 through Day 223

• Frequency and severity of serious AEs (SAEs), AEs leading to withdrawal, AEs of special interest (AESI), and medically attended AEs (MAAEs)

  Day 1 through Day 382

• GMT of HI antibodies against H5N8 strain - Persistence

  Day 202, Day 382

• GMT of HI antibodies against H5N6 strain - Persistence

  Day 202

Study Arms (3)

Arm A

EXPERIMENTAL

Eligible subjects who have been randomized to receive aH5N8c on Day 1, Day 22 and Day 202

Biological: aH5N8c on Day 1; Biological: aH5N8c on Day 22; Biological: aH5N8c on Day 202

Arm B

EXPERIMENTAL

Eligible subjects who have been randomized to receive aH5N8c on Day 1, aH5N6c on Day 22, and aH5N8c on Day 202

Biological: aH5N8c on Day 1; Biological: aH5N6c on Day 22; Biological: aH5N8c on Day 202

Arm C

EXPERIMENTAL

Eligible subjects who have been randomized to receive aH5N6c on Day 1 and aH5N8c on Day 22 and Day 202

Biological: aH5N6c on Day 1; Biological: aH5N8c on Day 22; Biological: aH5N8c on Day 202

Interventions

aH5N8c on Day 1 BIOLOGICAL

MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N8 vaccine (aH5N8c) for intramuscular administration, containing intermediate dose H5N8 hemagglutinin + standard dose MF59 (approximately 0.5 mL total volume)

Arm A; Arm B

aH5N6c on Day 1 BIOLOGICAL

MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular administration, containing intermediate dose H5N6 hemagglutinin + standard dose MF59 (approximately 0.5 mL total volume)

Arm C

aH5N8c on Day 22 BIOLOGICAL

MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N8 vaccine (aH5N8c) for intramuscular administration, containing intermediate dose H5N8 hemagglutinin + standard dose MF59 (approximately 0.5 mL total volume)

Arm A; Arm C

aH5N6c on Day 22 BIOLOGICAL

MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N6 vaccine (aH5N6c) for intramuscular administration, containing intermediate dose H5N6 hemagglutinin + standard dose MF59 (approximately 0.5 mL total volume)

Arm B

aH5N8c on Day 202 BIOLOGICAL

MF59-adjuvanted cell-culture derived subunit inactivated monovalent A/H5N8 vaccine (aH5N8c) for intramuscular administration, containing intermediate dose H5N8 hemagglutinin + standard dose MF59 (approximately 0.5 mL total volume)

Arm A; Arm B; Arm C

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 on the day of informed consent.
• Individuals who or whose legally acceptable representative(s) have voluntarily given written 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 which they intend to use for at least 30 days before the first study vaccination and plan to do so until 2 months after the last study vaccination.
• Individuals must provide a baseline blood sample prior to randomization and 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.
• 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 resulting from:
• Clinical conditions.
• Systemic administration of corticosteroids at a dose ≥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 AESI.
• Received immunoglobulins with immunomodulating effects or any blood products within 180 days prior to informed consent.
• Individuals who previously received an H5 influenza vaccine or have a known history of H5 influenza infection prior to enrollment.
• Received an investigational or non-registered medicinal product within 30 days prior to informed consent or are unwilling to refuse participation in another clinical study at any time during the conduct of this study.
• 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 individual 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 any of the 3 scheduled study vaccinations.

Sponsors & Collaborators

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

Study Sites (9)

Cullman Clinical Trials

Cullman, Alabama, 35055, United States

Location

Lifeline Primary Care

Lilburn, Georgia, 30047, United States

Location

Georgia Clinic

Norcross, Georgia, 30092, United States

Location

Velocity Clinical Research

Sioux City, Iowa, 51106, United States

Location

Velocity Clinical Research

Baton Rouge, Louisiana, 70809, United States

Location

Velocity Clinical Research

Grand Island, Nebraska, 68803, United States

Location

Velocity Clinical Research

Norfolk, Nebraska, 68701, United States

Location

Medical Care LLC

Elizabethton, Tennessee, 37643, United States

Location

Cope Family Medicine

Bountiful, Utah, 84010, United States

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Orthomyxoviridae Infections; RNA Virus Infections; Respiratory Tract Diseases

Study Officials

• Therapeutic Area Head

  Seqirus

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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 a 2:1:1 ratio to Treatment Arm A, B, or C, respectively, and will receive two priming doses of the allocated aH5N8c/aH5N6c vaccine 3 weeks apart, ie, at Day 1 and Day 22, and a booster dose of aH5N8c vaccine at Day 202.

Study Record Dates

• First Submitted: May 4, 2023
• First Posted: May 25, 2023
• Study Start: June 7, 2023
• Primary Completion: April 25, 2024
• Study Completion: September 25, 2024
• Last Updated: December 13, 2024

Record last verified: 2024-12

Locations

US (9)