A Study of mRNA-1083 (SARS-CoV-2 and Influenza) Vaccine in Healthy Adult Participants, ≥50 Years of Age

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. The Per Protocol Immunogenicity Set (PPIS) included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative reverse transcription polymerase chain reaction (RT-PCR) test for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.

SARS-CoV-2 strain included Omicron XBB.1.5 antibody. The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion was defined as a Day 29 postinjection level ≥1:40 if Baseline was <1:10 or a 4-fold or greater rise if Baseline was ≥1:10 in anti-hemagglutinin (HA) antibodies measured by HAI assay. The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.

SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Seroresponse was defined as a Day 29 postinjection level ≥4-fold rise if Baseline was ≥lower limit of quantification (LLOQ) or ≥4×LLOQ if Baseline value was <LLOQ in the nAb values measured by PsVNA. LLOQ was 38 arbitrary unit (AU)/milliliter (mL). The PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.

Solicited ARs (local and systemic) were reported by participants 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. 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.

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. A Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.

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 COVID-19 and visits to healthcare practitioners external to the study site. 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. A Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is located in the "Reported Adverse Events" section.

Influenza A strains included H1N1 and H3N2 and 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. PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.

SARS-CoV-2 strain included Omicron XBB.1.5 antibody. 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. PPIS included all randomized participants who received study intervention, complied with the timing of immunogenicity blood sample collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. The PPIS for MN assay included a subset of randomized participants who received study intervention to be tested for MN, complied with the timing of immunogenicity blood sampling collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.

Influenza A strains included H1N1 and H3N2 and 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. The PPIS for MN assay included a subset of randomized participants who received study intervention to be tested for MN, complied with the timing of immunogenicity blood sampling collections to have both Baseline and Day 29 assessments using a window of -7 to +14 days, had no major dosing error, had negative RT-PCR test for influenza and SARS-CoV-2 on Day 1, and had no major protocol deviations or conditions/medications that affected the immune response.

A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, irrespective of its perceived relationship to the study drug. The Investigator assessed the causality by determining whether there was a reasonable possibility that the death was related to the study drug, using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable AND/OR the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable.

A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, irrespective of its perceived relationship to the study drug. The Investigator assessed the causality by determining whether there was a reasonable possibility that the death was related to the study drug, using the following classifications: Not related: There was not a reasonable possibility of a relationship to the study drug. The temporal sequence of the death relative to administration of the study drug was not reasonable AND/OR the death was more likely explained by a cause other than the study drug. Related: There was a reasonable possibility of a relationship to the study drug. There was evidence of exposure to the study drug. The temporal sequence of the death relative to the administration of the study drug was reasonable.