A Study of mRNA-1010 Seasonal Influenza Vaccine in Adults

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

Time frame: Day 29

Population: The Per Protocol Immunogenicity Set (PPIS) included all randomized participants who received any study vaccination, who had baseline and Day 29 antibody assessment via HAI assay, complied with the immunogenicity testing schedule, and had no significant protocol deviations that impacted key or critical data. Number Analyzed = participants evaluable for specified categories.

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: The Safety Set included all participants who were randomized and received any study vaccination.

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: The Solicited Safety Set included all randomized participants who received any study vaccination and contributed any solicited AR data, that is, had at least 1 post-baseline solicited safety assessment.

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 participants who were randomized and received any study vaccination.

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

Time frame: Day 29

Population: The PPIS included all randomized participants who received any study vaccination, who had baseline and Day 29 antibody assessment via HAI assay, complied with the immunogenicity testing schedule, and had no significant protocol deviations that impacted key or critical data. Number Analyzed = participants evaluable for specified categories.

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 PPIS included all randomized participants who received any study vaccination, who had baseline and Day 29 antibody assessment via HAI assay, complied with the immunogenicity testing schedule, and had no significant protocol deviations that impacted key or critical data. Number Analyzed = participants evaluable for specified categories.

A protocol-defined ILI was determined by the occurrence of at least 1 respiratory illness symptom concurrently with at least 1 systemic symptom, or the occurrence of any 2 or more respiratory symptoms. Respiratory symptoms included sore throat, cough/rhinorrhea/nasal congestion (≥1 of the 3 symptoms count as 1 respiratory symptom), sputum production, wheezing, or difficulty breathing. Systemic symptoms included body temperature \>37.2 degrees Celsius (°C) (\>99 degrees Fahrenheit \[°F\]), chills, tiredness, headache, myalgia, nausea/vomiting, or diarrhea.

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

Population: The Modified Intent-to-Treat (mITT) Set included all participants who were randomized and received any study vaccination and who provided any follow-up for ILI beginning at least 14 days following administration of study intervention.

A CDC-defined ILI was defined as body temperature ≥37.8°C (100°F) accompanied by cough and/or sore throat.

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

Population: The mITT Set included all participants who were randomized and received any study vaccination and who provided any follow-up for ILI beginning at least 14 days following administration of study intervention.

A protocol-defined ILI was determined by the occurrence of at least 1 respiratory illness symptom concurrently with at least 1 systemic symptom, or the occurrence of any 2 or more respiratory symptoms. Respiratory symptoms included sore throat, cough/rhinorrhea/nasal congestion (≥1 of the 3 symptoms count as 1 respiratory symptom), sputum production, wheezing, or difficulty breathing. Systemic symptoms included body temperature \>37.2°C (\>99°F), chills, tiredness, headache, myalgia, nausea/vomiting, or diarrhea.

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

Population: The mITT Set included all participants who were randomized and received any study vaccination and who provided any follow-up for ILI beginning at least 14 days following administration of study intervention. 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified categories.

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

Time frame: Day 29

Population: The PPIS included all randomized participants who received any study vaccination, who had baseline and Day 29 antibody assessment via HAI assay, complied with the immunogenicity testing schedule, and had no significant protocol deviations that impacted key or critical data. Number Analyzed = participants evaluable for specified categories.