A Study of mRNA-1010 Seasonal Influenza Vaccine in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of mRNA-1010 Seasonal Influenza Vaccine in Adults (NCT05415462), a randomized phase 3 study. The primary outcome is Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibodies at Day 29, as Measured by Hemagglutination Inhibition (HAI) Assay for Vaccine-matched Influenza A and B Strains.

2. Clinical Question

3. Trial Design

This was a completed Phase 3, randomized, stratified, observer-blind, active-controlled study in adults 18 years and older. The registry record lists the allocation as randomized, the model as parallel, and masking as quadruple. Its official title describes the study as observer-blind; the registry does not explain how that wording relates to the listed masking category.

The planned enrollment was 6102. Participants were assigned to receive one intramuscular dose of mRNA-1010 or one intramuscular dose of Fluarix Tetra on Day 1. The comparator was an active vaccine rather than a placebo. The registry record identifies seasonal influenza as the condition under study and lists ModernaTX, Inc. as the sponsor.

The primary immunogenicity endpoint was measured at Day 29. It concerned geometric mean titers of anti-HA antibodies measured by HAI assay against vaccine-matched influenza A and B strains. The listed seasonal strains were H1N1 and H3N2 for influenza A, and Victoria-lineage and Yamagata-lineage for influenza B. The study's primary objectives also included safety and reactogenicity.

Secondary outcomes included counts of participants with RT-PCR-confirmed protocol-defined or CDC-defined influenza-like illness, including analyses in older age groups; the percentage with HAI titer at least 1:40 at Day 29; and geometric mean fold rise in anti-HA antibodies. The registry record lists ten outcome measures and eight analyses, but those counts do not by themselves establish how outcomes were prioritized or how testing was controlled. The study start date was 2022-06-06, the primary completion date was 2023-09-04, and the status is completed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 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.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The Randomization Set included all participants who were randomly assigned to treatment, regardless of the participants' vaccination status in the study.

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibodies at Day 29, as Measured by Hemagglutination Inhibition (HAI) Assay for Vaccine-matched Influenza A and B Strains, measured over Day 29.

The primary endpoint is the geometric mean titer (GMT) of anti-hemagglutinin antibodies at Day 29, measured by hemagglutination inhibition (HAI) assay. Hemagglutinin is a target measured in the antibody response to influenza strains; the endpoint records antibody titers against the vaccine-matched strains. The registry specifies influenza A H1N1 and H3N2 and influenza B Victoria-lineage and Yamagata-lineage.

In general, a geometric mean summarizes measurements that are positive and often skewed, using a logarithmic scale before averaging and converting back. It can describe the central antibody response without treating large values as having the same influence they would have on an arithmetic mean. It does not show how many individuals crossed a particular threshold, how widely individual responses varied, or whether participants experienced clinical influenza. Those questions require other outcomes, such as the listed HAI threshold and influenza-like illness measures.

The endpoint is paired with a 95% confidence interval in the registry outcome description. In general, a confidence interval conveys the uncertainty around an estimate under the assumptions of the analysis. The registry record does not report the GMT estimates, confidence limits, or a between-group comparison, so the magnitude and precision of the primary endpoint cannot be assessed from the reported information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Random allocation is intended, in general, to make treatment assignment independent of participant characteristics at the time of assignment. This supports a fair group comparison when the allocation process is carried out as planned and follow-up and analysis are handled appropriately. The registry labels the study randomized and stratified, but does not report the stratification factors, sequence-generation method, allocation concealment procedures, or the details of implementation. Those methods are not reported in the registry record.

The parallel design means the record describes distinct groups receiving the study vaccine or active comparator. Each group was scheduled for one intramuscular dose on Day 1. The study is described as observer-blind in its official title, while the masking entry is quadruple. In general, masking can reduce the influence of knowledge of assignment on participant experience, clinical observation, and outcome assessment. The registry record does not identify which roles were masked or explain the difference in wording between observer-blind and quadruple masking.

The primary endpoint uses a geometric mean titer. In general, geometric means are suited to measurements whose distribution is right-skewed: the analysis takes logarithms of the measurements, averages on that scale, and transforms the result back. This limits the disproportionate effect that a few very large values can have on an arithmetic mean. Interpretation still depends on the definition of the analysis population, the handling of measurements outside assay limits, and the statistical model. Those details are not reported in the registry record.

The endpoint description identifies a 95% confidence interval as its measure of dispersion. In general, a confidence interval describes uncertainty around an estimated quantity under a specified statistical model and sampling framework. It is not a range containing a fixed proportion of individual participants' titers, and it does not by itself answer whether two groups differ. A between-group estimate and its interval would be needed to describe the direction, magnitude, and precision of the contrast. Such estimates are not reported in the registry record.

The primary analysis population is called the Per Protocol Immunogenicity Set. Its description includes randomized participants who received any study vaccination, had baseline and Day 29 HAI assessments, complied with the immunogenicity testing schedule, and had no significant protocol deviations affecting key or critical assessments. In general, a per-protocol population can focus on participants with usable measurements and adherence to specified conditions, but exclusions can affect how representative the estimate is of all randomized participants. The registry's population wording is truncated, and further inclusion and exclusion rules are not reported.

The registry identifies both immunogenicity and safety as primary objectives, but it does not report the full statistical analysis plan. The planned estimands, model specifications, transformations, covariate adjustments, treatment of missing values, and rules for deriving analysis sets are not reported in the registry record. Nor does the record describe interim analyses or a stopping rule. These omissions mean the analysis cannot be reproduced or fully appraised from the information listed.

Multiplicity arises when multiple outcomes, strains, time points, or group comparisons are tested. In general, conducting many tests without accounting for their number can increase the chance of at least one apparently unusual result. Methods such as hierarchical testing or adjusted significance thresholds can address that issue, but the appropriate strategy depends on a prespecified testing plan. The registry lists several strain-specific primary targets and secondary outcomes, but does not report a multiplicity procedure or the ordering of hypotheses. No conclusion about multiplicity control can therefore be drawn.

For safety, the record gives counts of participants affected by serious adverse events and other adverse events, as well as deaths. In general, event counts and participant counts answer different questions: a participant may experience more than one event, while a participant count indicates whether at least one qualifying event occurred. The registry labels these entries as participant counts affected. Definitions, exposure-adjusted analyses, event timing, and attribution procedures are not reported in the registry record. Seriousness is not equivalent to severity or proof of causation.

The record includes planning assumptions for a separate sample-size illustration: a two-sided significance level of 0.05, equal allocation, a normal approximation, and a target effect stated as a fraction of the observed effect. In general, such a calculation asks how many participants per arm would be needed under its assumptions to detect a specified effect with a chosen power. It is a planning illustration, not observed power and not evidence of the trial's design rationale. No numerical planning results are reported in the registry record, and the trial's own sample-size justification is not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple immunogenicity targets, including matched influenza A and B strains, alongside several secondary outcomes. It does not state how those hypotheses were ordered, whether one endpoint or strain had priority for inference, or whether a multiplicity adjustment was planned. In general, when several tests are performed, a prespecified strategy helps distinguish confirmatory findings from exploratory ones and controls the interpretation of repeated testing. The statistical plan for multiplicity is not reported in the registry record.

Missing-data handling is also not reported. The primary analysis population description requires baseline and Day 29 HAI assessments and adherence to the testing schedule, but the record does not say how missing measurements were handled, how many participants lacked assessments, or whether any imputation or sensitivity analyses were used. Excluding participants without the required measurements can make the analyzed group differ from the randomized group; the direction and effect of any such difference cannot be inferred without results and analysis details.

The PPIS description is incomplete in the registry record. Additional population definitions, exclusions, and the relationship between the immunogenicity and safety populations are not reported. The record also does not describe a full intention-to-treat analysis or explain which population was used for each listed outcome. These omissions matter because different analysis populations can answer different questions and yield different estimates.

Interim analyses, stopping rules, and the sponsor's sample-size justification are not reported in the registry record. The available planning assumptions describe a sample-size illustration based on the observed effect, not the trial's own design justification. No reported information establishes whether that illustration corresponds to the original design process.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection (0.4%), pneumonia (0.3%), cholelithiasis (0.2%), acute myocardial infarction (0.2%), septic shock (0.1%).

The safety record lists 3048 participants at risk for serious adverse events in the Fluarix Quadrivalent 60 ug group, with 131 affected, and 3035 at risk in the mRNA-1010 50 ug group, with 132 affected. For other adverse events, the listed figures are 3048 at risk and 809 affected in the Fluarix group, and 3035 at risk and 803 affected in the mRNA-1010 group. Death counts are 18 and 10, respectively.

These are participant counts, not counts of every event experienced, and the record does not provide a causal attribution for the events. In general, serious adverse events are a regulatory category based on consequences such as hospitalization or other serious outcomes; seriousness is distinct from symptom intensity and does not prove that vaccination caused the event. The registry record does not report event timing, individual clinical narratives, causes of death, or an assessment of relatedness.

The record lists urinary tract infection at 0.4%, pneumonia at 0.3%, cholelithiasis at 0.2%, acute myocardial infarction at 0.2%, septic shock at 0.1%, and ischaemic stroke at 0.1% among the top serious terms. The population or calculation details behind these percentages are not reported. These figures should be read as registry-listed event terms, not as causal conclusions or a complete safety profile.

12. What the Result Does, and Does Not, Mean

The study was designed to compare Day 29 antibody titers after a single dose of mRNA-1010 or an active influenza vaccine comparator in adults. It also had safety and reactogenicity objectives. The posted information identifies the intended comparison and provides some safety counts, but does not report the primary GMT estimates or confidence intervals. As a result, it does not establish the magnitude or precision of the antibody response in either group.

The record names secondary measures of antibody response and influenza-like illness, but outcome definitions alone do not demonstrate an observed effect. Numerical results for these measures are not reported in the registry record. The listed Day 29 HAI threshold and geometric mean fold rise are different kinds of immunogenicity summaries from GMT; none can be substituted for another without the relevant results and analysis details.

The safety counts describe participants recorded as affected, and the listed serious-event terms describe reported event categories. They do not, on their own, show that vaccination caused an event or that any apparent count difference is statistically reliable. The registry record does not provide sufficient detail about timing, adjudication, relatedness, or causes of death to support a more specific safety interpretation.

In general, a randomized comparison can support causal interpretation when assignment, follow-up, outcome ascertainment, and analysis are appropriately conducted. The registry record gives limited information about these procedures and does not provide the statistical plan or detailed results. Thus, the design description should not be mistaken for evidence of a particular outcome, and completion of the study does not imply a favorable or unfavorable result.

The conclusions that can be drawn are correspondingly narrow: the trial compared two active vaccine groups, used Day 29 HAI GMT as its primary immunogenicity endpoint, and recorded the safety counts stated in the record. The primary result, statistical uncertainty, multiplicity approach, and handling of missing data are not reported in the registry record. No treatment recommendation follows from these registry entries.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly stated endpoint and the absence of its numerical result in the registry record. The endpoint is a Day 29 geometric mean titer for anti-HA antibodies against matched influenza A and B strains, with a 95% confidence interval specified. Without the estimates and intervals, readers cannot assess either the size of the antibody responses or how precisely they were measured.

The active-controlled, randomized, parallel design defines the intended comparison: one dose of mRNA-1010 against one dose of Fluarix Tetra. The record also states stratification and masking, but gives limited detail on how those features were implemented. For statistical interpretation, design labels establish the broad framework; they do not replace analysis methods, population definitions, or outcome estimates.

Multiple strains and several secondary outcomes create a need for careful prespecification and interpretation. In general, when related outcomes are tested, a clear hierarchy or adjustment strategy helps readers understand which findings are confirmatory. The registry record does not describe such a strategy. It also does not report the missing-data rules or a complete statistical analysis plan, limiting the ability to assess how robust any future interpretation would be.

The safety entries illustrate why event counts need context. Counts of participants affected, listed percentages for serious-event terms, and death counts describe different aspects of the record; none alone establishes causation. A complete statistical reading would require outcome definitions, timing, analysis populations, and uncertainty measures, which are not reported in the registry record.

The study therefore offers a useful example of how registry design details can be informative while still leaving key inferential questions unanswered. Distinguishing protocol objectives, observed estimates, and the precision of those estimates is essential to a restrained statistical interpretation.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting efficacy is that numerical primary endpoint results are not reported in the registry record. No GMT values, confidence limits, or formal between-group result are available in the listed information. The secondary outcome names likewise do not include numerical findings, so neither immunogenicity nor influenza-like illness results can be assessed.

The primary outcome covers multiple vaccine-matched strains, and the record does not reduce it to one comparison. It does not specify which strain-specific result, if any, was designated for a primary inferential decision. The multiplicity strategy and complete statistical analysis plan are not reported, making it difficult to know how any results should be interpreted across strains and outcomes.

The PPIS description is truncated, and the record does not report complete analysis-population definitions, missing-data methods, or sensitivity analyses. It also does not state the stratification factors, detailed masking procedures, or the statistical models used. These omissions limit reproducibility and make it difficult to judge how the estimates relate to all randomized participants.

The safety information is limited to participant counts and a list of top serious-event terms with percentages. Event timing, relatedness assessments, causes of death, and detailed event definitions are not reported. The safety group labels also differ from the intervention names in the study description: “Fluarix Quadrivalent 60 ug” appears in the safety record, while “Fluarix Tetra” is used for the comparator. The registry record does not explain that naming difference.

Finally, the registry record does not report the trial's own sample-size justification, interim analyses, or stopping rules. The stated assumptions for a sample-size illustration do not fill those gaps and should not be interpreted as observed power or as proof of the original design rationale.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of mRNA-1010 Seasonal Influenza Vaccine in Adults — NCT05415462.
• Registry record last updated 2024-09-24; status last verified 2024-08.
• Results first posted 2024-09-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT05415462 is a completed Phase 3 randomized, stratified, observer-blind, active-controlled, parallel study sponsored by ModernaTX, Inc. It enrolled adults 18 years and older, with planned enrollment of 6102. Participants received one intramuscular dose of mRNA-1010 or Fluarix Tetra on Day 1.

The primary immunogenicity endpoint was Day 29 GMT of anti-HA antibodies measured by HAI assay against vaccine-matched influenza A and B strains. The primary objectives also included safety and reactogenicity. Secondary outcomes included HAI threshold and fold-rise measures and RT-PCR-confirmed influenza-like illness.

The registry record lists safety counts and serious-event terms, but does not report numerical primary endpoint results, confidence limits, or a full statistical analysis plan. The study start date was 2022-06-06, primary completion was 2023-09-04, and the status is completed.