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

Seqirus260 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

260

Conditions

Influenza, Human Influenza in Birds

Interventions

aH5N6c on Day 1BIOLOGICAL

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)

aH5N6c on Day 22BIOLOGICAL

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

Placebo on Day 22BIOLOGICAL

Saline placebo (sterile, 0.5 mL) given 3 weeks after the aH5N6c vaccination

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (18)

Optimal Research, LLC

Huntsville, Alabama, United States

Clinical Research Consortium Arizona

Tempe, Arizona, United States

California Research Foundation

San Diego, California, United States

Clinical Research Consulting, LLC

Milford, Connecticut, United States

Innovative Research of West Florida, Inc.

Clearwater, Florida, United States

Optimal Research, LLC

Melbourne, Florida, United States

Great Lakes Clinical Trials LLC

Chicago, Illinois, United States

Heartland Research Associates, LLC

Wichita, Kansas, United States

The Center for Pharmaceutical Research

Kansas City, Missouri, United States

Sundance Clinical Research, LLC

St Louis, Missouri, United States

...and 8 more locations

Outcomes

Primary Outcomes

Geometric Mean Titer (GMT) of hemagglutination inhibition (HI) antibodies against H5N6 strain

GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2

Time frame: Day 1, Day 8, Day 22, Day 43

Geometric Mean Fold Increase (GMFI) of HI antibodies against H5N6 strain

GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 compared to pre-vaccination (Day 1)

Time frame: Day 1, Day 8, Day 22, Day 43

Percentage of subjects with HI titers ≥1:40 against H5N6 strain

Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2

Time frame: Day 1, Day 8, Day 22, Day 43

Percentage of subjects with seroconversion against 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

Time frame: Day 8, Day 22, Day 43

Secondary Outcomes

GMT of HI antibodies against H5N1 strain

GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2

Time frame: Day 1, Day 8, Day 22, Day 43, Day 202

GMFI of HI antibodies against 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)

Time frame: Day 1, Day 8, Day 22, Day 43, Day 202

Percentage of subjects with HI titers ≥1:40 against H5N1 strain

Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2

Time frame: Day 1, Day 8, Day 22, Day 43, Day 202

Percentage of subjects with seroconversion against 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

Time frame: Day 8, Day 22, Day 43, Day 202

GMT of HI antibodies against H5N6 strain

GMT 6 months post-vaccination 2

Time frame: Day 202

GMFI of HI antibodies against H5N6 strain

GMFI 6 months post-vaccination 2 compared to pre-vaccination (Day 1)

Time frame: Day 1, Day 202

Percentage of subjects with HI titers ≥1:40 against H5N6 strain

6 months post-vaccination 2

Time frame: Day 202

Percentage of subjects with seroconversion against 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

Time frame: Day 202

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

For 7 days following each vaccination

Time frame: Day 1 through Day 7 and Day 22 through Day 28

Frequency and severity of unsolicited AEs

For 3 weeks following each vaccination

Time frame: Day 1 through Day 43

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

From vaccination until study completion

Time frame: Day 1 through Day 202