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

Sponsor

Seqirus (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05422326

Collaborator

(none)

300

Enrollment

Locations

Arms

9.4

Anticipated Duration (Months)

16.7

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Influenza, Human Influenza in Birds Respiratory Tract Infections Infections Orthomyxoviridae Infections RNA Virus Infections Virus Diseases Respiratory Tract Diseases	Biological: aH5N6c on Day 1 Biological: aH5N6c on Day 22 Biological: Placebo on Day 22	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Eligible subjects, who received 2 doses of aH5N1c in the parent study V89_18 are randomized in a 1:1 ratio to group 1 (two aH5N6c vaccinations, 3 weeks apart) or group 2 (aH5N6c vaccination and placebo, 3 weeks apart). Eligible subjects, who received placebo in the parent study are allocated to group 3 (two aH5N6c vaccinations, 3 weeks apart).Eligible subjects, who received 2 doses of aH5N1c in the parent study V89_18 are randomized in a 1:1 ratio to group 1 (two aH5N6c vaccinations, 3 weeks apart) or group 2 (aH5N6c vaccination and placebo, 3 weeks apart). Eligible subjects, who received placebo in the parent study are allocated to group 3 (two aH5N6c vaccinations, 3 weeks apart).

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jul 18, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

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

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

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

Biological: aH5N6c on Day 22

Outcome Measures

Primary Outcome Measures

Geometric Mean Titer (GMT) of hemagglutination inhibition (HI) antibodies against H5N6 strain [Day 1, Day 8, Day 22, Day 43]
GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2
Geometric Mean Fold Increase (GMFI) of HI antibodies against H5N6 strain [Day 1, Day 8, Day 22, Day 43]
GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2 compared to pre-vaccination (Day 1)
Percentage of subjects with HI titers ≥1:40 against H5N6 strain [Day 1, Day 8, Day 22, Day 43]
Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks post-vaccination 2
Percentage of subjects with seroconversion against H5N6 strain [Day 8, Day 22, Day 43]
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

Secondary Outcome Measures

GMT of HI antibodies against H5N1 strain [Day 1, Day 8, Day 22, Day 43, Day 202]
GMT pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2
GMFI of HI antibodies against H5N1 strain [Day 1, Day 8, Day 22, Day 43, Day 202]
GMFI 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2 compared to pre-vaccination (Day 1)
Percentage of subjects with HI titers ≥1:40 against H5N1 strain [Day 1, Day 8, Day 22, Day 43, Day 202]
Pre-vaccination, 1 and 3 weeks post-vaccination 1, and 3 weeks and 6 months post-vaccination 2
Percentage of subjects with seroconversion against H5N1 strain [Day 8, Day 22, Day 43, Day 202]
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
GMT of HI antibodies against H5N6 strain [Day 202]
GMT 6 months post-vaccination 2
GMFI of HI antibodies against H5N6 strain [Day 1, Day 202]
GMFI 6 months post-vaccination 2 compared to pre-vaccination (Day 1)
Percentage of subjects with HI titers ≥1:40 against H5N6 strain [Day 202]
6 months post-vaccination 2
Percentage of subjects with seroconversion against H5N6 strain [Day 202]
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
Frequency and severity of solicited local and systemic adverse events (AEs) [Day 1 through Day 7 and Day 22 through Day 28]
For 7 days following each vaccination
Frequency and severity of unsolicited AEs [Day 1 through Day 43]
For 3 weeks following each vaccination
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 202]
From vaccination until study completion

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Optimal Research, LLC	Huntsville	Alabama	United States	35802
2	Clinical Research Consortium Arizona	Tempe	Arizona	United States	85283
3	California Research Foundation	San Diego	California	United States	92103
4	Clinical Research Consulting, LLC	Milford	Connecticut	United States	06460
5	Innovative Research of West Florida, Inc.	Clearwater	Florida	United States	33756
6	Optimal Research, LLC	Melbourne	Florida	United States	32934
7	Great Lakes Clinical Trials LLC	Chicago	Illinois	United States	60640
8	Heartland Research Associates, LLC	Wichita	Kansas	United States	67207
9	The Center for Pharmaceutical Research	Kansas City	Missouri	United States	64114
10	Sundance Clinical Research, LLC	Saint Louis	Missouri	United States	63141
11	Rochester Clinical Research, Inc	Rochester	New York	United States	14609
12	PMG Research of Raleigh	Raleigh	North Carolina	United States	27609
13	AccellaCare	Winston-Salem	North Carolina	United States	27103
14	Aventiv Research	Columbus	Ohio	United States	43213
15	Biogenics Research Institute	San Antonio	Texas	United States	78229
16	J. Lewis Research, Inc/Foothill Family Clinic North	Salt Lake City	Utah	United States	84109
17	J. Lewis Research, Inc/Foothill Family Clinic South	Salt Lake City	Utah	United States	84121
18	J. Lewis Research, Inc/Jordan River Family Medicine	South Jordan	Utah	United States	84095