Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA Vaccine Candidate Variations in Healthy Adults

An SAE was defined as any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. AESIs included thrombocytopenia, new onset of or worsening of the protocol specified neurologic diseases, anaphylaxis, and myocarditis/pericarditis. An MAAE is an AE that lead to an unscheduled visit to an healthcare practitioner. This included visits to a study site for unscheduled assessments (for example, abnormal laboratory follow-up, and/or coronavirus disease 2019 \[COVID-19\] and visits to healthcare practitioners external to the study site (for example, urgent care, primary care physician). Number of participants with SAEs, AESIs, MAAEs, and AEs leading to discontinuation up to the end of study (Day 181) are reported in this outcome measure.

Time frame: Day 1 to Day 181 (end of study [EOS])

Population: Safety Set included all participants who received 1 dose of study intervention. Participants were included in the study arm corresponding to the study intervention that they received.

Solicited ARs (local and systemic) were collected in an electronic diary (eDiary). Local ARs included: injection site pain, injection site erythema (redness), injection site swelling/induration (hardness), and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs included: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. All solicited ARs considered causally related to injection were graded 0-4 (per Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials); lower score indicates lower severity, and a higher score indicates greater severity. Note, not all solicited ARs were considered adverse events (AEs). The Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of serious AEs (SAEs) and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.

Time frame: 7 days post-vaccination

Population: Solicited Safety Set included all participants who received 1 dose of study intervention and contributed any solicited AR data (that is, had at least 1 post baseline solicited safety \[eDiary\] assessment). Participants were included in the study intervention group corresponding to the study intervention that they received.

An unsolicited AE was an AE that was not solicited using a participant diary and that was communicated by a participant who has signed the informed consent. An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time \[PT\]/partial thromboplastin time \[PTT\]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsened from baseline and was considered clinically significant in the medical and scientific judgment of the Investigator was recorded as an AE. Number of participants with unsolicited AEs (SAEs and non-serious AEs) up to 28 days post-vaccination are reported in this outcome measure.

Time frame: Up to 28 days post-vaccination

Population: Safety Set included all participants who received 1 dose of study intervention. Participants were included in the study arm corresponding to the study intervention that they received.

The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Fold-rise was calculated by dividing post-vaccination results by the baseline value. 95% confidence interval (CI) for GMFR was calculated based on the t distribution of the differences in the log-transformed values between analysis timepoint and baseline, then back transformed to the original scale for presentation.

Time frame: Baseline, Days 8, 29, 91, and 181

Population: Per-Protocol Set: all randomized participants who received study drug, complied with injection schedule, timing of immunogenicity blood sampling to have a baseline (Day 1), had at least 1 post injection assessment, had a Day 29 assessment that was within 22 days to 43 days after injection, had no important protocol deviations which impacted immune response, and did not use prohibited medication/nonstudy vaccines against influenza. 'Number analyzed'= participants evaluable for specified category.

Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. 95% CI was calculated based on the t-distribution of log-transformed values for GM titer, then back transformed to original scale for presentation.

Time frame: Days 1 (Baseline), 8, 29, 91, and 181

Population: Per-Protocol Set: all randomized participants who received study drug, complied with injection schedule, timing of immunogenicity blood sampling to have a baseline (Day 1), had at least 1 post injection assessment, had a Day 29 assessment that was within 22 days to 43 days after injection, had no important protocol deviations which impacted immune response, and did not use prohibited medication/nonstudy vaccines against influenza. 'Number analyzed'= participants evaluable for specified category.

Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroresponse was defined as (a) a post-vaccination antibody titer ≥ 4 \* lower limit of quantification (LLOQ) if baseline (Day 1) antibody titer was \< LLOQ or (b) a post-vaccination antibody titer ≥ 4-fold of baseline antibody titer if baseline antibody titer was ≥ LLOQ.

Time frame: Days 8, 29, 91, and 181

Population: Per-Protocol Set: all randomized participants who received study drug, complied with injection schedule, timing of immunogenicity blood sampling to have a baseline (Day 1), had at least 1 post injection assessment, had a Day 29 assessment that was within 22 days to 43 days after injection, had no important protocol deviations which impacted immune response, and did not use prohibited medication/nonstudy vaccines against influenza. 'Number analyzed'= participants evaluable for specified category.