A Study of mRNA-1010 Seasonal Influenza Vaccine in Adults 50 Years Old and Older

Protocol-defined ILI: The presence of body temperature ≥37.5 degrees celsius (°C) (≥99.5 degrees fahrenheit \[°F\]), accompanied by at least one of the respiratory illness symptoms (sore throat, cough, sputum production, wheezing, or difficulty breathing) and a positive Reverse Transcription Polymerase Chain Reaction (RT-PCR) for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: Per-Protocol (PP) Set included all participants in the Modified Intent-to-Treat (mITT) Set (all randomized participants who received any study intervention except those who discontinued from the study prior to 14 days following administration of study intervention) who did not have major protocol deviations that could adversely impact efficacy, for example, disease or therapeutic intervention that might cause suboptimal response to the study intervention.

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 361) are reported in this outcome measure.

Time frame: Day 1 through Day 361 (Month 12)

Population: Safety Set included all randomized participants who received any study intervention. Participants were included in the vaccination group corresponding to the study intervention that 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. 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 randomized participants who received any study intervention and contributed to any solicited AR data.

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 randomized participants who received any study intervention. Participants were included in the vaccination group corresponding to the study intervention that 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% 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: PPIS included all randomized participants in the biomarker subset who received any study intervention; had baseline and Day 29 antibody assessment via HAI assay; complied with the immunogenicity testing schedule, and had no major protocol deviations that impacted the immunogenicity assessment.

Seasonal influenza A strains included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. 95% confidence interval (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: Day 29

Population: PP Immunogenicity Set (PPIS) included all randomized participants in the biomarker subset who received any study intervention; had baseline and Day 29 antibody assessment via HAI assay; complied with the immunogenicity testing schedule, and had no major protocol deviations that impacted the immunogenicity assessment.

CDC-defined ILI: The presence of temperature ≥37.8°C \[≥100°F\], accompanied by at least one of the respiratory illness symptoms (cough and/or sore throat) and a positive RT-PCR for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: PP Set included all participants in the mITT Set (all randomized participants who received any study intervention except those who discontinued from the study prior to 14 days following administration of study intervention) who did not have major protocol deviations that could adversely impact efficacy, for example, disease or therapeutic intervention that might cause suboptimal response to the study intervention.

Protocol-defined ILI: The presence of body temperature ≥37.5°C (≥99.5°F), accompanied by at least one of the respiratory illness symptoms (sore throat, cough, sputum production, wheezing, or difficulty breathing) and a positive RT-PCR for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: PP Set included all participants in the mITT Set (all randomized participants who received any study intervention except those who discontinued from the study prior to 14 days following administration of study intervention) who did not have major protocol deviations that could adversely impact efficacy, for example, disease or therapeutic intervention that might cause suboptimal response to the study intervention.

CDC-defined ILI: The presence of temperature ≥37.8°C \[≥100°F\], accompanied by at least one of the respiratory illness symptoms (cough and/or sore throat) and a positive RT-PCR for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: PP Set included all participants in the mITT Set (all randomized participants who received any study intervention except those who discontinued from the study prior to 14 days following administration of study intervention) who did not have major protocol deviations that could adversely impact efficacy, for example, disease or therapeutic intervention that might cause suboptimal response to the study intervention.

CDC-defined ILI: The presence of temperature ≥37.8°C \[≥100°F\], accompanied by at least one of the respiratory illness symptoms (cough and/or sore throat) and a positive RT-PCR for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: As pre-specified, the data for this outcome measure was not collected and analyzed.

Protocol-defined ILI: The presence of body temperature ≥37.5°C (≥99.5°F), accompanied by at least one of the respiratory illness symptoms (sore throat, cough, sputum production, wheezing, or difficulty breathing) and a positive RT-PCR for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: PP Set included all participants in the mITT Set (all randomized participants who received any study intervention except those who discontinued from the study prior to 14 days following administration of study intervention) who did not have major protocol deviations that could adversely impact efficacy, for example, disease or therapeutic intervention that might cause suboptimal response to the study intervention.

Protocol-defined ILI: The presence of body temperature ≥37.5°C (≥99.5°F), accompanied by at least one of the respiratory illness symptoms (sore throat, cough, sputum production, wheezing, or difficulty breathing) and a positive RT-PCR for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: As pre-specified, the data for this outcome measure was not collected and analyzed.

CDC-defined ILI: The presence of temperature ≥37.8°C \[≥100°F\], accompanied by at least one of the respiratory illness symptoms (cough and/or sore throat) and a positive RT-PCR for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: PP Set included all participants in the mITT Set (all randomized participants who received any study intervention except those who discontinued from the study prior to 14 days following administration of study intervention) who did not have major protocol deviations that could adversely impact efficacy, for example, disease or therapeutic intervention that might cause suboptimal response to the study intervention.

Protocol-defined ILI: The presence of body temperature ≥37.5°C (≥99.5°F), accompanied by at least one of the respiratory illness symptoms (sore throat, cough, sputum production, wheezing, or difficulty breathing) and a positive RT-PCR for influenza.

Time frame: 14 days post-vaccination through Day 181 (Month 6)

Population: PP Set included all participants in the mITT Set (all randomized participants who received any study intervention except those who discontinued from the study prior to 14 days following administration of study intervention) who did not have major protocol deviations that could adversely impact efficacy, for example, disease or therapeutic intervention that might cause suboptimal response to the study intervention.

Seroconversion was defined as either a Baseline HAI titer \<1:10 and a post-Baseline titer ≥1:40 or a Baseline HAI titer ≥1:10 and a minimum 4-fold rise in post-Baseline HAI antibody titer.

Time frame: Day 29

Population: PPIS included all randomized participants in the biomarker subset who received any study intervention; had baseline and Day 29 antibody assessment via HAI assay; complied with the immunogenicity testing schedule, and had no major protocol deviations that impacted the immunogenicity assessment.

Time frame: Day 29

Population: PPIS included all randomized participants in the biomarker subset who received any study intervention; had baseline and Day 29 antibody assessment via HAI assay; complied with the immunogenicity testing schedule, and had no major protocol deviations that impacted the immunogenicity assessment.