Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates

Conditions

• Influenza

Eligibility Criteria

Sex

ALL

Age

18 Years - 59 Years

Healthy Volunteers

Accepted

Interventions

• cH15/3 — BIOLOGICAL
  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).
• cH4/3 — BIOLOGICAL
  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 — BIOLOGICAL
  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 — BIOLOGICAL
  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.
• Saline — DRUG
  Sodium chloride solution.

Study Details

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.

Key Dates

First listed

Jul 14, 2026

Start date

Jul 17, 2026

Status verified

Jul 2026

Primary completion

Apr 12, 2027

Completion

Apr 12, 2027

Study Design

Enrollment

60 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

PREVENTION

Arms

• Experimental: Cohort 1, Arm1
  Healthy adults will receive 2 monovalent dose intramuscular injections. cH8/1 (25ug) chimeric Hemagglutinin (HA) is the first dose given on Day 1, followed by a second dose administered 57 days later with cH5 /1(25 ug). N = 10
• Experimental: Cohort 1, Arm2
  Healthy adults will receive 2 monovalent dose intramuscular injections. cH15/3 (25ug) chimeric HA is the first dose given on Day 1, followed by a second dose of cH4/3 (25ug), administered 57 days later. N = 10.
• Experimental: Cohort 1, Arm3
  Healthy adults will receive 2 low dose bivalent intramuscular injections. cH8/1(12.5ug) + cH15/3 (12.5ug) chimeric HA is the first dose given on Day 1, followed by a second dose of cH5/1 (12.5ug) + cH4/3(12.5 ug) administered 57 days later. N = 10.
• Experimental: Cohort 2, Arm4
  Healthy adults will receive a single high dose bivalent combination intramuscular injection along with a placebo dose. cH8/1(25ug) + cH15/3(25ug) will be administered on Day 1, followed by a placebo dose 57 days later. N = 10.
• Experimental: Cohort 2, Arm5
  Healthy adults will receive a single high dose bivalent combination intramuscular injection along with a placebo dose. cH5/1(25ug) + cH4/3(25ug) will be administered on Day 1, followed by a placebo dose 57 days later. N = 10.
• Experimental: Cohort 2, Arm6
  Healthy adults will receive 2 high dose bivalent intramuscular injections. cH8/1(25ug) + cH15/3 (25ug) is the first dose given on Day 1, followed by the second dose of cH5/1(25 ug) + cH4/3 (25 ug) administered 57 days later. N = 10.

Primary Outcome Measure

Geometric mean fold rise (GMFR) from baseline in HA-stalk specific titers by ELISA [ Time Frame: Day 1 through Day 85 ]

Central Contacts

• Meagan Deming
  14107068333
  [email protected]

Locations (1)

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