This is a phase 1, multicenter, randomized, double-blind trial of two influenza A/H5 mRNA-based vaccines on healthy adult participants, 18-49 years of age. Stage 1 will serve as the open-label, dose finding stage. The first 10 participants will receive 12.5 mcg of H5 AC-Anhui RNA vaccine (Group 1), and the second 10 participants will receive 25 mcg of H5 AC-Anhui RNA vaccine (Group 2). After Protocol Safety Review Team (PSRT) review of reactogenicity and safety data through Day 8 for both Groups 1 and 2, another 10 participants may be enrolled to receive 50 mcg of H5 AC-Anhui RNA vaccine (Group 3). Safety data from 7 days after dose 2 for Groups 1 and 2 participants will be reviewed by the PSRT prior to clearing Group 3 participants for the second dose of vaccine. Individual participants will be followed for approximately 6 months following the second dose of vaccine. The primary objective is to assess the safety of two doses of H5 AC-Anhui RNA vaccine or H5-Astrakhan RNA vaccine administered intramuscularly in healthy adults (18-49 years). Once the Day 36 data from Group 3 are reviewed by the PSRT, a dose will be chosen (12.5 mcg, 25 mcg, or 50 mcg) for advancement to Stage 2 where 50 participants will be randomized 1:1 to receive either H5 AC-Anhui RNA (Group 4) or H5 Astrakhan RNA (Group 5) in a double-blinded manner.
This is a multicenter, randomized, double-blind trial of two influenza A/H5 mRNA-based vaccines. The trial population consists of healthy adult participants, 18-49 years of age. Stage 1 will serve as the open-label, dose finding stage. The first 10 participants will receive 12.5 mcg of H5 AC-Anhui RNA vaccine (Group 1), and the second 10 participants will receive 25 mcg of H5 AC-Anhui RNA vaccine (Group 2). These groups will be enrolled sequentially without pause unless study halting rules are triggered. After Protocol Safety Review Team (PSRT) review of reactogenicity and safety data through Day 8 for both Groups 1 and 2, another 10 participants may be enrolled to receive 50 mcg of H5 AC-Anhui RNA vaccine (Group 3). Safety data from Day 36 (7 days after dose 2) for Groups 1 and 2 participants will be reviewed by the PSRT prior to clearing Group 3 participants for the second dose of vaccine. Once the Day 36 data from Group 3 are reviewed by the PSRT, a dose will be chosen (12.5 mcg, 25 mcg, or 50 mcg) for advancement to Stage 2 where 50 participants will be randomized 1:1 to receive either H5 AC-Anhui RNA (Group 4) or H5 Astrakhan RNA (Group 5) in a double-blinded manner. Participants will be randomized on the day of enrollment. Screening and enrollment can occur on the same day. Individual participants will be followed for approximately 6 months following the second dose of vaccine. The primary objective is to assess the safety of two doses of H5 AC-Anhui RNA vaccine or H5-Astrakhan RNA vaccine administered intramuscularly in healthy adults (18-49 years). The secondary objective is to assess the serum antibody responses to H5 AC-Anhui RNA vaccine or H5-Astrakhan RNA vaccine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
80
A nucleoside-modified mRNA vaccine encoding a stabilized, antigenically central hemagglutinin (HA) from influenza A(H5), based on A/Anhui/1/2005 (clade 2.3.4) with substitutions 222QL, 224GS, 156TA, and 134TA. The 2119-nt mRNA is encapsulated in lipid nanoparticles (LNPs) for intramuscular delivery.
The vaccine product consists of a monovalent nucleoside-modified mRNA that encodes a traditionally selected avian influenza HA. The H5 Astrakhan RNA encodes the HA from the clade 2.3.4.4b A/Astrakhan/3212/2020 virus.
0.9% Sodium Chloride Injection
Duke Vaccine and Trials Unit
Durham, North Carolina, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor College of Medicine
Houston, Texas, United States
Number and Percentage of participants experiencing any adverse events of special interest (AESI)
Time frame: Through 90 days after second vaccination
Number and Percentage of participants experiencing any medically attended adverse events (MAAE)
Time frame: Through 6 months following the second dose
Number and Percentage of participants experiencing any non-serious unsolicited adverse events (AEs)
Time frame: Through 28 days following each dose
Number and Percentage of participants experiencing any serious adverse events (SAE)
Time frame: Through 6 months following the second dose
Number and Percentage of participants experiencing new-onset chronic medical conditions (NOCMC)
Time frame: Through 6 months following the second dose
Number and Percentage of participants experiencing solicited local reactogenicity adverse events (AEs)
Time frame: Through 7 days following each dose
Number and Percentage of participants experiencing solicited systemic reactogenicity adverse events (AEs)
Time frame: Through 7 days following each dose
Number and Percentage of participants with clinical laboratory adverse events (AEs)
Time frame: Through 7 days following each dose
Geometric mean fold rise (GMFR) in Group 1-specific anti-stalk serum antibodies since pre-vaccination (Day 1)
Time frame: Day 8 through Day 57
Geometric mean fold rise (GMFR) in homologous and heterologous H5-specific Neut antibody since pre-vaccination (Day 1)
Time frame: Day 8 through Day 57
Geometric mean fold rise in homologous and heterologous H5-specific Hemagglutination Inhibition Antibody (HAI) antibody since pre-vaccination
Time frame: Day 8 through Day 57
Geometric mean titers of Group 1-specific anti-stalk serum antibodies
Time frame: Day 1 through Day 57
Geometric mean titers of homologous and heterologous H5-specific hemagglutinin inhibition (HAI) antibodies
Time frame: Day 1 through Day 57
Geometric mean titers of homologous and heterologous H5-specific neutralizing antibodies (Neut)
Time frame: Day 1 through Day 57
Number and Percentage of participants achieving Hemagglutination Inhibition Antibody (HAI) titer seroconversion since pre-vaccination (Day 1) against the homologous and heterologous H5-specific hemagglutinin
Seroconversion is defined as either a pre-vaccination titer \<1:10 and a post-vaccination titer \>/=1:40 or a pre- vaccination titer \>/=1:10 and a minimum four-fold rise in post-vaccination antibody titer
Time frame: Day 8 through Day 57
Number and Percentage of participants demonstrating Hemagglutination Inhibition Antibody (HAI) titer seroprotection against homologous and heterologous H5-specific hemagglutinin
Seroprotection defined as \>/=1:40 titer
Time frame: Day 1 through Day 57
The number and percentage of participants achieving Neut seroconversion since pre-vaccination (Day 1) against the homologous and heterologous H5-specific hemagglutinin
Seroconversion is defined as either a pre-vaccination titer \<1:10 and a post-vaccination titer \>/= 1:40 or a pre-vaccination titer \>/= 1:10 and a minimum four-fold rise in post-vaccination antibody titer
Time frame: Day 8 through Day 57
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