This is a Phase 1, randomized, controlled, dose-ranging clinical trial to assess the safety and immunogenicity of novel influenza A Group 1 and influenza A Group 2 mRNA chimeric hemagglutinin (HA) vaccine candidates given as intramuscular injections alone and in combination. A total of 60 healthy men and non-pregnant, non-breastfeeding women aged 18 through 59 years will be enrolled in one of 6 study arms. The 6 arms will consist of: 1) Sequential influenza A Group 1 mRNA chimeric hemagglutinin: cH8/1 (25 µg) followed by cH5/1 (25 µg), 2) Sequential influenza A Group 2 mRNA chimeric hemagglutinin: cH15/3 (25 µg) followed by cH4/3 (25 µg), 3) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (25 µg) followed by cH5/1 + cH4/3 (25 µg), 4) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (50 µg) followed by placebo, 5) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH5/1 + cH4/3 (50 µg) followed by placebo, 6) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (50 µg) followed by cH5/1 + cH4/3 (50 µg). The primary objectives are to evaluate safety and immunogenicity: 1) To assess the safety and reactogenicity of one or two doses of monovalent or bivalent Group 1 and 2 study products and 2) To describe the Group 1 and 2 anti-HA stalk IgG antibody responses of one or two doses of monovalent or bivalent Group 1 and 2 study products by ELISA.
This is a Phase 1, randomized, controlled, dose-ranging clinical trial to assess the safety and immunogenicity of novel influenza A Group 1 and influenza A Group 2 mRNA chimeric hemagglutinin (HA) vaccine candidates given as intramuscular injections alone and in combination. A total of 60 healthy men and non-pregnant, non-breastfeeding women aged 18 through 59 years will be enrolled in one of 6 study arms. The 6 arms will consist of: 1) Sequential influenza A Group 1 mRNA chimeric hemagglutinin: cH8/1 (25 µg) followed by cH5/1 (25 µg), 2) Sequential influenza A Group 2 mRNA chimeric hemagglutinin: cH15/3 (25 µg) followed by cH4/3 (25 µg), 3) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (25 µg) followed by cH5/1 + cH4/3 (25 µg), 4) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (50 µg) followed by placebo, 5) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH5/1 + cH4/3 (50 µg) followed by placebo, 6) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8/1 + cH15/3 (50 µg) followed by cH5/1 + cH4/3 (50 µg). The primary objectives are to evaluate safety and immunogenicity: 1) To assess the safety and reactogenicity of one or two doses of monovalent or bivalent Group 1 and 2 study products and 2) To describe the Group 1 and 2 anti-HA stalk IgG antibody responses of one or two doses of monovalent or bivalent Group 1 and 2 study products by ELISA. The secondary objective is to describe the Group 1 and Group 2 anti-hemagglutinin stalk Immunoglobulin G (IgG) antibody response of one or two doses of monovalent or bivalent Group 1 and 2 study products by ELISA at a later timepoints.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
60
The cH15/3 RNA study product encodes for a novel chimeric hemagglutinin comprised of an H15 HA head domain derived from influenza A/wedge-tailed shearwater/Western Australia/2576/1979 (H15N9) and the conserved stem domain derived from influenza A/Hong Kong/2014 (H3N2) (GenBank: OQ349633). The cH15/3 RNA is encapsulated in LNPs for delivery. The LNP is comprised of 4 lipid components: ionizable lipid (ALC-0315), distearoylphosphatidylcholine (DSPC), cholesterol (non-animal derived), and PEG lipid (ALC-0159).
The cH4/3 RNA encodes a novel chimeric hemagglutinin comprised of an H4 head domain from A/duck/Czechoslovakia/1956 (H4N6) and a conserved stem domain from A/Hong Kong/2014 (H3N2) (GenBank: OQ349617), delivered via lipid nanoparticles (LNPs) containing ionizable lipid (ALC-0315), distearoylphosphatidylcholine (DSPC), cholesterol (non-animal derived), and PEG lipid (ALC-0159).
cH5/1N1 is a H1N1 influenza vaccine: egg grown split inactivated influenza virus vaccines containing chimeric hemagglutinins (HAs). The chimeric viruses contain the globular heads of exotic viruses- and the HA stem domain and neuraminidase protein from currently circulating seasonal H1N1.
cH8/1N1 is a H1N1 influenza vaccine: egg grown split inactivated influenza virus vaccines containing chimeric hemagglutinins (HAs). The chimeric viruses contain the globular heads of exotic viruses- and the HA stem domain and neuraminidase protein from currently circulating seasonal H1N1.
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University of Maryland, School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, United States
Geometric mean fold rise (GMFR) from baseline in HA-stalk specific titers by ELISA
Time frame: Day 1 through Day 85
Geometric mean titer (GMT) by ELISA
Time frame: Day 1 Through Day 85
Number and percentage of participants with greater than or equal to a 2-, 4-, and 10-fold rise from baseline in Hemagglutinin (HA)-stalk specific titers by ELISA
Time frame: Day1 through Day 85
Occurrence of Adverse Events of Special Interest (AESIs)
Time frame: Day 1 through Day 240
Occurrence of Guillain-Barre Syndrome (GBS)
Time frame: Through Day 240
Occurrence of hematological or biochemical laboratory adverse events
Time frame: Day 8 through Day 64
Occurrence of laboratory confirmed influenza A infection
Time frame: Through Day 240
Occurrence of Medically-Attended Adverse Events (MAAEs)
Time frame: Through Day 240
Occurrence of New-Onset Chronic Medical Conditions (NOCMCs)
Time frame: Through Day 240
Occurrence of Serious Adverse Events (SAEs)
Time frame: Through Day 240
Occurrence of solicited local adverse events (AEs)
Time frame: Day 1 through Day 64
Occurrence of solicited systemic adverse events (AEs)
Time frame: Day 1 through Day 64
Occurrence of unsolicited adverse events (AEs)
Time frame: Day 1 through Day 85
Geometric mean fold-rise (GMFR) from baseline in Hemagglutinin (HA) stalk specific titers by ELISA
Time frame: Day 240
Hemagglutinin (HA)-stalk specific geometric mean titer (GMT) by ELISA
Time frame: Day 240
Number and percentage of participants with greater than or equal to a 2-, 4-, and 10-fold rise from baseline in Hemagglutinin (HA) -stalk specific titers by ELISA
Time frame: Day 240
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