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

1. Trial at a Glance

This page covers the registry results for Study of mRNA-1010 Seasonal Influenza Vaccine in Adults (NCT05827978), a randomized phase 3 study. The primary outcome is Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibody Levels as Measured by Hemagglutination Inhibition (HAI).

2. Clinical Question

3. Trial Design

This is a randomized, stratified, observer-blind, active-controlled Phase 3 study with a parallel-group model. The registry record identifies triple masking. It was conducted in three parts, A, B and C, and reports enrollment of 8411. The study status is completed. The recorded start date is 2023-04-17, and the primary completion date is 2024-06-24.

The study compares mRNA-1010 with a licensed quadrivalent inactivated seasonal influenza vaccine. The intervention descriptions specify one intramuscular dose on Day 1 in each arm. For the safety record, the comparator groups are named Fluarix QIV in Parts A and B and Fluzone HD QIV in Part C. These are active comparators rather than a placebo arm.

The main endpoint concerns antibody titers measured at Day 29. The registry describes a Per-Protocol Immunogenicity Set for this endpoint: randomized participants who received the planned dose, met the Baseline and Day 29 testing schedule, and had no significant protocol deviations affecting key or critical data. The record does not provide enough detail to characterize further eligibility criteria, the stratification factors, or how masking was implemented.

The registry lists eight outcome measures and no analysis records. It does not report the GMT results, confidence intervals, or a defined single contrast for the primary endpoint. Thus, the design can be described, but a quantitative conclusion about the immune-response comparison cannot be drawn from the posted results described in this record.

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 the planned dose of study intervention, complied with the immunogenicity testing schedule for Baseline and Day 29, and had no significant protocol deviations that impacted key or critical data. Participants were analyzed according to the group to which they were randomized.

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: Randomization set included all participants who were randomly assigned to the study intervention, regardless of the participants' study intervention status in the study. Participants were analyzed according to the group to which they were randomized.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibody Levels as Measured by Hemagglutination Inhibition (HAI), measured over Day 29.

The primary endpoint is the geometric mean titer (GMT) of anti-hemagglutinin (HA) antibody levels measured by hemagglutination inhibition (HAI), at Day 29. The influenza A strains were H1N1 and H3N2; the influenza B strains were Victoria and Yamagata. The registry defines the unit as titer and identifies a 95% confidence interval as the measure of dispersion.

In general, a geometric mean summarizes measurements that are naturally analyzed on a multiplicative scale. It is often used for antibody titers because titer values can span a broad range and fold changes are meaningful. A confidence interval conveys the uncertainty around an estimated mean; it is not itself a measure of the range of individual participants' titers.

The registry states how values outside the assay's quantification range were handled: values below the lower limit of quantification were replaced by 0.5 times that limit, while values above the upper limit were converted to the upper limit. Such rules allow values to be included in the endpoint calculation, but they also mean the resulting summary depends partly on the specified assay limits and substitutions.

The Day 29 endpoint is a measure of antibody response, not a direct clinical outcome such as influenza illness. The registry record does not report the GMT estimates, their confidence intervals, or a primary endpoint comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the GMT summarize?

Geometric means are used for measurements that are interpreted multiplicatively. In general, when values are analyzed on a logarithmic scale, the mean on that scale can be transformed back to the original scale as a geometric mean. This is useful for antibody titers because proportional changes and fold rises are often more informative than arithmetic differences. The registry names GMT as the endpoint, but does not report the calculation details beyond its rules for values outside the quantification range.

The endpoint is based on HAI measurements of anti-HA antibodies. HAI is an assay-based measure, so it is not a direct count of infections or a measure of clinical illness. The four named strains are H1N1, H3N2, Victoria and Yamagata. Since the primary outcome is not reduced to one comparison and no analysis records are listed, the record does not establish whether a single summary across strains was intended or how any strain-level results should be combined.

How should a confidence interval be read?

In general, a confidence interval describes the uncertainty in an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision for that estimate than a wider interval, but neither interval width nor the interval alone shows whether an effect is clinically important. For a comparison, an interval would need to be tied to a clearly defined contrast, such as a ratio or difference, and interpreted on that scale.

The primary endpoint identifies a 95% confidence interval, but no GMT estimate or interval is reported in the registry record. Therefore, the endpoint's stated uncertainty measure cannot be used to judge precision for the trial's antibody results. No p-value or inferential test for the primary comparison is reported either.

Why specify assay limits?

Laboratory assays have lower and upper limits of quantification. Values below or above those limits cannot be treated as exact measurements in the same way as values inside the measurable range. The registry states that below-limit values were replaced by 0.5 times the lower limit and above-limit values were set to the upper limit. These substitutions make a defined endpoint calculation possible, while imposing assumptions about observations at the boundaries. The record does not report how many measurements were affected by either rule.

What does randomization contribute?

In general, random assignment is intended to reduce systematic differences between groups at the start of a study, so observed outcome differences can be interpreted more fairly as comparisons of assigned interventions. Stratification can be used to organize randomization across selected factors. The registry identifies randomization and stratification, but does not report the factors used, the allocation procedure, or the resulting baseline balance. It therefore does not support a more detailed assessment of these features.

The trial is also described as observer-blind and triple-masked. These labels indicate that masking was part of the design, but the registry record does not specify which individuals were masked or how masking was maintained. No further assumptions about the masked roles or implementation are warranted.

What are the planning illustrations?

Planning illustrations based on an observed effect are not observed power and do not replace the trial's own design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations express participants per arm for 80% power or another stated power level; time-to-event illustrations express total events. The registry record does not report the trial's own sample-size justification, and no primary effect estimate is available to support interpretation of an observed-effect illustration.

These assumptions are generic planning inputs, not evidence that the trial was designed or analyzed using those assumptions. They should not be read as showing that an effect was observed, that a particular power was achieved, or that a result is statistically conclusive.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures and no analysis records. The primary endpoint description concerns multiple influenza strains, and the record notes that the primary outcome has several categories or time points and is not reduced to one comparison. The secondary outcomes include the percentage of participants with an HAI titer at least 1:40 and geometric mean fold-rise of postinjection anti-HA antibodies for influenza measured by HAI.

When a study examines multiple outcomes, strains, time points, or groups, the chance of at least one apparently notable result can increase if many tests are conducted. General approaches to this issue include prespecifying a testing hierarchy, adjusting significance thresholds, or interpreting estimates with appropriate caution. The registry record does not report whether multiplicity was addressed, which tests were prespecified, or how any family of comparisons was defined. No multiplicity method should therefore be inferred.

The record describes the Per-Protocol Immunogenicity Set used for the primary endpoint. It includes randomized participants who received the planned dose, complied with Baseline and Day 29 immunogenicity testing, and had no significant protocol deviations affecting key or critical data. A per-protocol population can differ from an analysis of everyone randomized, and exclusions may affect interpretation. The registry record does not give the number analyzed, the reasons for exclusion, or an intention-to-treat analysis population for this endpoint.

Missing-data methods are not reported in the registry record. The assay-limit substitutions are described, but those are not a general missing-data strategy. The record does not state how missing measurements, missed visits, or withdrawals were handled, or whether sensitivity analyses were performed. These omissions limit assessment of the analysis population and the robustness of the endpoint results.

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

Serious events with the highest arm-level rate: pneumonia (0.3%), cellulitis (0.2%), deep vein thrombosis (0.2%), death (0.2%), acute myocardial infarction (0.1%).

The serious adverse event figures are listed separately for each study part and group. In Part A, the record reports 21 among 1180 for Fluarix QIV and 27 among 1220 for mRNA-1010. In Part B, it reports 22 among 1488 for Fluarix QIV and 25 among 1492 for mRNA-1010. In Part C, it reports 38 among 1490 for Fluzone HD QIV and 41 among 1502 for mRNA-1010. These are group-specific counts and denominators, not a statistical comparison.

The record also lists deaths by group: 1 for Part A Fluarix QIV and 5 for Part A mRNA-1010; 2 for Part B Fluarix QIV and 3 for Part B mRNA-1010; 1 for Part C Fluzone HD QIV and 3 for Part C mRNA-1010. The registry does not provide a causal assessment for these deaths, so the counts should not be interpreted as evidence that an intervention caused an event.

The listed serious-event terms with their reported percentages include Pneumonia at 0.3%, Cellulitis at 0.2%, Deep vein thrombosis at 0.2%, Death at 0.2%, Acute myocardial infarction at 0.1%, and Pulmonary embolism at 0.1%. The record does not provide term-specific group comparisons or uncertainty intervals. These figures describe reported events in this record and do not, by themselves, establish comparative safety.

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

This record describes a randomized Phase 3 comparison of mRNA-1010 with licensed seasonal influenza vaccines in adults. Its primary endpoint is the Day 29 geometric mean titer of anti-HA antibodies measured by HAI. The record identifies the strains, the assay-limit rules, and a Per-Protocol Immunogenicity Set, but it does not report the primary GMT estimates, confidence intervals, or a single comparison.

That absence matters for interpretation. A trial design and a defined endpoint explain what investigators intended to measure; they do not reveal the observed endpoint values. Without estimates and their uncertainty, the direction, magnitude and precision of any immune-response difference cannot be assessed from this registry record. The listed secondary outcome measures do not substitute for missing primary results.

The safety record provides group-specific serious adverse event and death counts, as well as selected serious-event terms and percentages. These figures are descriptive. Without comparative analyses, uncertainty estimates, or causal assessments, they do not establish whether event frequencies differ between interventions or whether an event was caused by an intervention.

In general, an antibody endpoint and a clinical endpoint answer different questions. Antibody titers describe an immune response measured by an assay; they are not themselves counts of influenza cases. This record does not report a clinical influenza outcome or establish how antibody measurements relate to clinical protection.

The record therefore allows readers to understand the broad trial structure and the types of measurements made, while leaving key questions about results unanswered. It does not justify a conclusion that one intervention produced higher or lower antibody titers, or that comparative safety was established. Those conclusions require analyses and estimates that are not reported in the registry record.

13. Why This Trial Matters Statistically

Several statistical features make this trial a useful example of the distinction between a clearly defined endpoint and an interpretable result. The endpoint is a geometric mean antibody titer at a specified time, with strains and assay-boundary rules identified. Such detail helps readers understand what the measurement represents and how laboratory values outside the quantification range were treated.

The trial is randomized, stratified, observer-blind, active-controlled and parallel-group, as described in the registry record. These design features are relevant to how a comparison is structured, but they do not replace reporting of the estimates and analyses. Randomization does not make an unreported result available, and a stated confidence-interval method does not convey precision without an interval.

The record also illustrates why outcomes and populations need clear specification. It lists multiple outcome measures, describes a per-protocol immunogenicity population, and notes that the primary outcome has several categories or time points rather than a single comparison. Interpretation depends on knowing which contrasts were planned, how multiple tests were handled, how missing measurements were addressed, and which participants contributed to each analysis. Those details are not reported.

Finally, group-specific serious adverse event and death counts are not equivalent to a formal comparative safety analysis. Their interpretation depends on group definitions, follow-up, event classification and uncertainty, among other considerations. The record gives some descriptive information but no comparative estimates. Statistically, the central lesson is to separate what a registry describes about design and measurement from what its posted results actually permit readers to conclude.

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.

A central limitation is that the registry record does not report the primary GMT results or confidence intervals. It also does not provide a single primary comparison, and no analysis records are listed. Without those estimates, neither the magnitude nor precision of the immune-response results can be assessed.

The primary endpoint covers several influenza strains, but strain-specific estimates and the approach to any combined interpretation are not reported. The record does not state the multiplicity strategy, the statistical tests used, or whether any hierarchy among outcomes was prespecified. Although it lists eight outcome measures, the corresponding analysis details are not available in the registry record.

The Per-Protocol Immunogenicity Set is described, but the number of participants in that population, the exclusions, and the flow from randomization to analysis are not reported. The record does not describe missing-data methods or sensitivity analyses. It also does not report the number of assay measurements below or above quantification limits, so the impact of the stated substitutions cannot be assessed.

The trial has three parts, and the safety record names different comparator vaccines across those parts. The record does not provide a comparative statistical analysis that accounts for the parts or explains how safety results should be combined. The serious adverse event and death figures are descriptive, with no reported uncertainty intervals or causal assessments.

Further design details, including stratification factors and the implementation of masking, are not reported in the registry record. The trial's sample-size justification and statistical plan are also not reported. These gaps limit independent evaluation of the design assumptions and of how fully the posted outcomes answer the study question.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of mRNA-1010 Seasonal Influenza Vaccine in Adults — NCT05827978.
• Registry record last updated 2025-07-10; status last verified 2025-06.
• Results first posted 2025-07-10.
• 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

The registry record describes a completed randomized, stratified, observer-blind, active-controlled Phase 3 study of mRNA-1010 in adults 18 years and older. It includes Parts A, B and C, reports enrollment of 8411, and specifies a single intramuscular dose on Day 1 for the intervention and comparator arms.

The primary endpoint is the Day 29 geometric mean titer of anti-HA antibodies measured by HAI for H1N1, H3N2, Victoria and Yamagata. The endpoint description gives assay-limit substitutions and identifies the Per-Protocol Immunogenicity Set. Eight outcome measures are listed, but no analysis records are listed, and the primary results are not reported.

Group-specific serious adverse event and death counts are available, along with selected serious-event terms and percentages. These are descriptive figures; the record does not report comparative safety analyses or causal assessments. Multiplicity handling, missing-data methods, and the trial's statistical plan are not reported in the registry record.