A Study of mRNA-1011.1, mRNA-1011.2, and mRNA-1012.1 Candidate Seasonal Influenza Vaccines 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 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: The Safety Set included all randomly assigned participants who received the study vaccination. Participants were included in the vaccination group corresponding to what they actually 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.

Time frame: 7 days post-vaccination

Population: The Solicited Safety Set included all randomly assigned participants who received the study vaccination and contributed any solicited AR data. Participants were included in the vaccination group corresponding to what they actually received.

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: The Safety Set included all randomly assigned participants who received the study vaccination. Participants were included in the vaccination group corresponding to what they actually 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, Day 29

Population: The PP Set included all randomly assigned participants who received study vaccination, complied with the injection schedule, complied with the timings of immunogenicity blood sampling to have a baseline and at least the Day 29 post-injection assessment, had no RT-PCR-confirmed influenza infection prior to Day 29 visit and had no major protocol deviations that impacted the immune response. Participants were analyzed according to the group to which they were randomized.

Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage.

Time frame: Day 29

Population: Per-Protocol (PP) Set included all randomly assigned participants who received study vaccination, complied with the injection schedule, complied with the timings of immunogenicity blood sampling to have a baseline and at least the Day 29 post-injection assessment, had no RT-PCR-confirmed influenza infection prior to Day 29 visit and had no major protocol deviations that impacted the immune response. Participants were analyzed according to the group to which they were randomized.

Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion was defined as a postbaseline titer ≥1:40 if baseline is \<1:10 or a 4-fold or greater rise if baseline is ≥1:10 in anti-HA antibodies measured by HAI assay.

Time frame: Day 29

Population: The PP Set included all randomly assigned participants who received study vaccination, complied with the injection schedule, complied with the timings of immunogenicity blood sampling to have a baseline and at least the Day 29 post-injection assessment, had no RT-PCR-confirmed influenza infection prior to Day 29 visit and had no major protocol deviations that impacted the immune response. Participants were analyzed according to the group to which they were randomized.