A Phase 1a/b Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study with an Open-Label Active-Controlled Phase, to Evaluate the Safety and Immunogenicity of Centi-Flu 01 in Healthy Adults 18 Years of Age and Older

This is a double-blind, placebo-controlled, dose-escalating study conducted in healthy adult volunteers. The study will be conducted in 2 parts, with each part having a double-blind period and an open-label period. The phase 1a study will evaluate the safety and immunogenicity of Centi-Flu 01 in healthy adults aged 18 to 64 (Cohorts 1 and 2), and healthy adults egual to or greater than age 65 (Cohorts 3 and 4). In this part of the study, 6 different dosing regimens of Centi-Flu 01 will be evaluated in a double-blind manner. Up to 180 participants will be enrolled across a total of 4 cohorts, with each cohort consisting of 3 groups. Sentinel dosing will also be utilized in each cohort. Dose and age escalation will be based on the principle that to proceed with the lowest doses in older adults and to proceed with higher doses in the younger adults, preliminary safety of the lowest doses in younger adults will first be established. Each group will enroll up to 15 participants with 12 participants randomised to receive Centi-Flu 01 and 3 participants randomised to receive placebo. Participants will receive a single intramuscular (IM) dose in the upper deltoid region of the arm of Centi-Flu 01 or placebo (according to their randomisation for the double-blind portion of the study) on Days 1 and 56, at the following dose levels: Cohort 1: Group 1) - First dose - 10µg administered as a single IM injection on Day 1, Second dose - 10µg administered as a single IM injection on Day 56 Cohort 1: Group 2) - First dose - 30µg administered as a single IM injection on Day 1, Second dose - Placebo administered as a single IM injection on Day 56 Cohort 1: Group 3) - First dose - 30µg administered as a single IM injection on Day 1, Second dose - 30µg administered as a single IM injection on Day 56 Cohort 2: Group 4) - First dose - 60µg administered as a single IM injection on Day 1, Second dose - Placebo administered as a single IM injection on Day 56 Cohort 2: Group 5) - First dose - 60µg administered as a single IM injection on Day 1, Second dose - 60µg administered as a single IM injection on Day 56 Cohort 2: Group 5) - First dose - 90µg administered as a single IM injection on Day 1, Second dose - Placebo administered as a single IM injection on Day 56 Cohort 3: Group 7) - First dose - 10µg administered as a single IM injection on Day 1, Second dose - 10µg administered as a single IM injection on Day 56 Cohort 3: Group 8) - First dose - 30µg administered as a single IM injection on Day 1, Second dose - Placebo administered as a single IM injection on Day 56 Cohort 3: Group 9) - First dose - 30µg administered as a single IM injection on Day 1, Second dose - 30µg administered as a single IM injection on Day 56 Cohort 4: Group 10) - First dose - 60µg administered as a single IM injection on Day 1, Second dose - Placebo administered as a single IM injection on Day 56 Cohort 5: Group 11) - First dose - 60µg administered as a single IM injection on Day 1, Second dose - 60µg administered as a single IM injection on Day 56 Cohort 6: Group 12) - First dose - 90µg administered as a single IM injection on Day 1, Second dose - Placebo administered as a single IM injection on Day 56 Following completion of Day 64 assessments, the study will be unblinded, and those who were randomised to receive placebo will receive a seasonal vaccination during the next influenza seasonal vaccination timeframe. Adaptive design elements of the study will be used to determine whether participants will receive a booster dose of Centi-Flu 01 (if they were randomised to Centi-Flu 01) or the seasonal vaccination (if they were randomised to placebo) 1 year following their initial vaccination. At 1 year following the initial immunisation with Centi-Flu 01, an adaptive design decision based on immunogenicity data, including sera collected at Month 11 (Day 335), will determine whether a booster dose of Centi-Flu 01 will be administered. Therefore, there may or may not be a third immunisation. Different groups may differ in this regard depending on the durability and magnitude of their immune responses to the priming regimen, age cohort, dose level received, and emerging hemagglutination inhibition (HAI) data reviewed as part of the adaptive design. Participants who initially received Centi-Flu 01 as a first dose and then received placebo as a second dose (ie those receiving 30 or 60µg Centi-Flu 01 mRNA) will not be given a commercial vaccine unless it is determined by serology that they did not make an adequate HAI response to the regimen. In that case when the serologic data is available they will receive a commercial vaccine. Strategies to assess and monitor adherence to the intervention include observation and recording of the vaccine administration in appropriate drug accountability records and measurement of the serologic HAI responses to the vaccine compared to baseline.