A Phase 1/2, Randomized, Observer-blind, Active-Control Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-based Influenza and SARS-CoV-2 Multi-component Vaccines in Healthy Adults

Part 2: Geometric Mean Titer (GMT) of Antibodies for Influenza at Day 29, as Measured by Hemagglutination Inhibition (HAI) Assay

时间窗: Day 29

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Antibody values reported as below the lower limit of quantification (LLOQ) were replaced by 0.5 \* LLOQ. Values greater than the upper limit of quantification (ULOQ) were converted to the ULOQ. LLOQ = 10 and ULOQ = 3620 for Influenza A H1N1 antibody, LLOQ = 10 and ULOQ = 5120 for Influenza A H3N2 antibody, LLOQ = 10 and ULOQ = 1356 for Influenza B/Victoria-lineage antibody, and LLOQ = 10 and ULOQ = 1280 for Influenza B/Yamagata-lineage antibody. 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values for geometric mean (GM) titer, then back transformed to the original scale for presentation. Arms based on the applicable vaccine for this Outcome Measure.

Part 2: GM Concentration of Antibodies for SARS-CoV-2 at Day 29, as Measured by Pseudovirus Neutralization Assay (PsVNA)

时间窗: Day 29

SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Antibody values reported as below the LLOQ are replaced by 0.5 \* LLOQ. Values greater than the ULOQ are converted to the ULOQ. LLOQ = 38 and ULOQ = 6960 arbitrary units (AU)/milliliter (mL) for SARS-CoV-2 Omicron XBB.1.5 antibody. 95% CI was calculated based on the t-distribution of the log-transformed values for GM concentration, then back transformed to the original scale for presentation. Arms based on the applicable vaccine for this Outcome Measure.

Parts 1 and 2: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)

时间窗: Up to 7 days after study injection

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.

Parts 1 and 2: Number of Participants With Unsolicited Adverse Events (AEs) and Severe AEs

时间窗: Up to 28 days after study injection

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. Severity for all unsolicited AEs was determined by the Investigator based upon medical judgment and graded as Mild, Moderate or Severe. Number of participants with unsolicited AEs (SAEs and non-serious AEs) and severe 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.

Parts 1 and 2: Number of Participants With Unsolicited Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs), and AEs Leading to Study Discontinuation

时间窗: Day 1 through Day 181

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 were protocol-defined medical concepts. 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 study discontinuation up to 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.

Part 2: Geometric Mean Fold-Rise (GMFR) of Antibodies for Influenza at Day 29, as Measured by HAI Assay

时间窗: Day 29

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Antibody values reported as below the LLOQ were replaced by 0.5 \* LLOQ. Values greater than the ULOQ were converted to the ULOQ. LLOQ = 10 and ULOQ = 3620 for Influenza A H1N1 antibody, LLOQ = 10 and ULOQ = 5120 for Influenza A H3N2 antibody, LLOQ = 10 and ULOQ = 1356 for Influenza B/Victoria-lineage antibody, and LLOQ = 10 and ULOQ = 1280 for Influenza B/Yamagata-lineage antibody. 95% CI was calculated based on the t-distribution of the log-transformed values for GMFR values, then back transformed to the original scale for presentation. Arms based on the applicable vaccine for this Outcome Measure.

Part 2: GMFR of Antibodies for SARS-CoV-2 at Day 29, as Measured by PsVNA

时间窗: Day 29

SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Antibody values reported as below the LLOQ are replaced by 0.5 \* LLOQ. Values greater than the ULOQ are converted to the ULOQ. LLOQ = 38 and ULOQ = 6960 AU/mL for SARS-CoV-2 Omicron XBB.1.5 antibody. 95% CI was calculated based on the t-distribution of the log-transformed values for GMFR values, then back transformed to the original scale for presentation. Arms based on the applicable vaccine for this Outcome Measure.

Part 2: Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay

时间窗: Baseline to Day 29

Influenza A strains included H1N1 and H3N2 and influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion was defined as a pre-vaccination HAI titer \<1:10 and a post-vaccination HAI titer ≥1:40 or a pre-vaccination HAI titer ≥1:10 and a minimum 4-fold rise in post-vaccination HAI antibody titer. Arms based on the applicable vaccine for this Outcome Measure.

Part 2: SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA

时间窗: Baseline to Day 29

SARS-CoV-2 strain included Omicron XBB.1.5 antibody. Seroresponse was defined as an increase from below the LLOQ to ≥4 \* LLOQ if Baseline neutralizing antibody (nAb) level was \< LLOQ, or ≥4-fold rise if Baseline nAb level was ≥ LLOQ. LLOQ = 38 and ULOQ = 6960 AU/mL for SARS-CoV-2 Omicron XBB.1.5 antibody. Arms based on the applicable vaccine for this Outcome Measure.