A Study to Evaluate the Safety and Immune Response of mRNA-1345, a Vaccine Targeting Respiratory Syncytial Virus (RSV), When Co-administered With a Fluzone HD, in Adults ≥65 Years of Age

Antibody values reported as below lower limit of quantification (LLOQ) were replaced by 0.5\*LLOQ. Values greater than the upper limit of quantification (ULOQ) were replaced by the ULOQ. LLOQ was 13 international units (IU)/milliliter (mL) and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B.

Time frame: Day 22 (for Arm 1) and Day 43 (for Arm 2)

Population: The Per-protocol (PP) Set included all randomized participants who received the assigned study intervention dose according to protocol, complied with immunogenicity blood sampling to have a baseline and at least 1 post-injection assessment, and had no important protocol deviations that impacted the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.

Influenza A strains included H1N1 and H3N2 and influenza B strains included Austria and Phuket strains. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B.

Time frame: Day 22

Population: The PP Set included all randomized participants who received the assigned study intervention dose according to protocol, complied with immunogenicity blood sampling to have a baseline and at least 1 post-injection assessment, and had no important protocol deviations that impacted the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

A MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner. An AESI is an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor are required. 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, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.

Time frame: Day 1 through Day 202

Population: The Safety Set included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug they actually received.

Solicited ARs were collected in an electronic diary (eDiary). Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered adverse events (AEs). 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: Within 7 days after Day 1 injection

Population: Day 1 Solicited Safety Set included all randomized participants who received any study intervention on Day 1 and contributed any solicited ARs data from the time of study injection on Day 1 through the following 6 days. Participants were included in the treatment arm corresponding to the study drug they actually received.

Solicited ARs were collected in an eDiary. Local ARs: injection site pain, erythema (redness), swelling/induration (hardness); and axillary (underarm) swelling or tenderness ipsilateral to the side of injection. Systemic ARs: fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, and chills. Note, not all solicited ARs were considered AEs. Investigator reviewed whether the solicited AR was also to be recorded as an AE. A Summary of SAEs and nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.

Time frame: Within 7 days after Day 22 injection

Population: Day 22 Solicited Safety Set included all randomized participants who received any study intervention on Day 22 and contributed any solicited ARs data from the time of study injection on Day 22 through the following 6 days. Participants were included in the treatment arm corresponding to the study drug 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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.

Time frame: Up to 21 days after Day 1 injection

Population: The Safety Set included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug 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 PT/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. A summary of SAEs and all nonserious AEs (Other), regardless of causality, is located in the Reported Adverse Events section.

Time frame: Up to 21 days after Day 22 injection

Population: The Safety Set included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug they actually received.

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: Day 22 (for Arm 1) or Day 43 (for Arm 2)

Population: The PP Set included all randomized participants who received the assigned study intervention dose according to protocol, complied with immunogenicity blood sampling to have a baseline and at least 1 post-injection assessment, and had no important protocol deviations that impacted the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.

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: Day 22

Population: The PP Set included all randomized participants who received the assigned study intervention dose according to protocol, complied with immunogenicity blood sampling to have a baseline and at least 1 post-injection assessment, and had no important protocol deviations that impacted the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

≥2-fold increase from baseline at participant level was defined as a change from below the LLOQ to equal or above 2 \* LLOQ, or at least a 2-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B.

Time frame: Day 22 (Arm 1) or Day 43 (Arm 2)

Population: The PP Set included all randomized participants who received the assigned study intervention dose according to protocol, complied with immunogenicity blood sampling to have a baseline and at least 1 post-injection assessment, and had no important protocol deviations that impacted the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.

Influenza A strains included H1N1 and H3N2 and influenza B strains included Austria and Phuket strains. Seroconversion at a participant level was defined as a titer ≥1:40 if baseline is \< 1:10 or at least a 4-fold increase from baseline if baseline was ≥1:10. Antibody values reported as below LLOQ were replaced by 0.5\*LLOQ. Values greater than the ULOQ were replaced by the ULOQ. LLOQ was 10 and ULOQ was 2560 for Influenza A. LLOQ was 10 and ULOQ was 640 for Influenza B.

Time frame: Day 22

Population: The PP Set included all randomized participants who received the assigned study intervention dose according to protocol, complied with immunogenicity blood sampling to have a baseline and at least 1 post-injection assessment, and had no important protocol deviations that impacted the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint.

Seroresponse at a participant level was defined as a change from below the LLOQ to equal or above 4 \* LLOQ, or at least a 4-fold increase if baseline was equal to or above the LLOQ. LLOQ was 13 IU/mL and ULOQ was 259061 IU/mL for RSV-A. LLOQ was 10 IU/mL and ULOQ was 112476 for RSV-B.

Time frame: Baseline to Day 22 (for Arm 1) or Day 43 (for Arm 2)

Population: The PP Set included all randomized participants who received the assigned study intervention dose according to protocol, complied with immunogenicity blood sampling to have a baseline and at least 1 post-injection assessment, and had no important protocol deviations that impacted the immune response. 'Overall number of participants analyzed' = participants evaluable for this endpoint. 'Number analyzed' = participants evaluable for specified category.

A death that occurred during the study or that came to the attention of the investigator during the study was reported to the Sponsor, whether or not it was considered related to study drug. The investigator assessed causality (that is, whether there is a reasonable possibility that the study drug caused the death). The relationship was characterized 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. The death was more likely explained by the study drug than by another cause.

Time frame: Day 1 through Day 202

Population: The Safety Set included all randomized participants who received any study intervention. Participants were included in the treatment arm corresponding to the study drug they actually received.