Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates

Summary

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.

Conditions

• Influenza

Interventions

BIOLOGICAL

cH15/3

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).

BIOLOGICAL

cH4/3

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).

BIOLOGICAL

cH5/1N1

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.

BIOLOGICAL

cH8/1N1

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.

DRUG

Saline

Sodium chloride solution.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

59 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2026-07-17

Primary Completion

2027-04-12

Completion

2027-04-12

FDA Drug

Yes

Countries

• United States

Study Locations