A Study to Find the Dose and Assess the Immune Response and Safety of a Vaccine Against Influenza in Healthy Younger and Older Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Find the Dose and Assess the Immune Response and Safety of a Vaccine Against Influenza in Healthy Younger and Older Adults (NCT06431607), a randomized phase 2 study. The primary outcome is Part 1 YA: Geometric Mean Titer (GMT) of Antigen 1 Antibody Titer.

2. Clinical Question

3. Trial Design

This was a Phase 2a randomized, quadruple-masked, parallel-group dose-finding study of mRNA-based multivalent seasonal influenza vaccine candidates. It enrolled 845 participants and is listed as completed. The study concerned healthy adults aged 18 years and older, with separate younger-adult and older-adult groups. The registry lists the study start as 2024-05-23 and primary completion as 2024-12-27.

The trial had two parts, with candidate and comparator arms differing across parts and age groups. In Part 1, younger adults were allocated among four mRNA candidate arms and a Flu D-QIV comparator arm. Older adults in Part 1 received one of four listed mRNA candidate interventions or Fluzone HD Quadrivalent. Part 2 compared GSK5800544A with Flu D-TIV in younger adults and with Fluzone HD in older adults. Each arm description specifies a single dose administered at Day 1.

Random allocation can help balance participant characteristics across assigned groups, while masking is intended to limit bias in care, reporting, or assessment. The registry labels masking as quadruple but does not describe which roles were masked. A parallel-group design means participants were assigned to an intervention group rather than described as crossing between treatments. The record does not report the allocation ratio, sequence-generation method, or operational details of masking.

The study is described as dose-finding, but the registry information used for this account does not state the dose levels or explain how a candidate dose was selected. The record also does not report a sample-size justification or the statistical decision rules used to compare candidates. The overall enrollment should not be treated as the number contributing to every individual outcome: the primary analysis is described as using a Per Protocol Set, and arm-specific denominators vary in the posted safety counts.

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.

Before assignment: A total of 845 participants were included in enrolled set out of which only 833 were included in exposed set and started the study.

Only the first 6 of 14 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Per Protocol Set (PPS), which included all eligible participants who received the study intervention dose according to the protocol, had immunogenicity results at Day 29 , without intercurrent conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination before Day 29. Only participants with data available for specified analysis at the specified timepoints are included.

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.

Only the first 6 of 15 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part 1 YA: Geometric Mean Titer (GMT) of Antigen 1 Antibody Titer, measured over At Day 29.

The primary endpoint is the geometric mean titer of Antigen 1 antibody for Part 1 younger adults, assessed at Day 29. Antibody titer is a quantitative measure of the antibody response detected by an assay. A geometric mean summarizes such measurements on a multiplicative scale; it is commonly used when titers are skewed and changes are naturally considered proportionally rather than as equal arithmetic increments. This is general statistical context, not confirmation of the exact calculation steps used in this trial.

The registry names a 95% confidence interval as the dispersion measure and describes two assay versions: one using egg-propagated influenza virus and one using cell-propagated influenza virus. The confidence interval is intended to express uncertainty around an estimated geometric mean. In general, an interval’s width reflects how precisely the estimate has been determined under the analysis assumptions; it is not a range that guarantees the true value lies within it.

The endpoint is an immunogenicity measure, not a clinical influenza outcome. It does not by itself quantify illness, prevention of infection, or duration of protection. The registry record does not report the numerical geometric mean titers or their confidence intervals, so the observed antibody response and its precision cannot be assessed from the record. Nor does the record give enough detail to establish how results from the two assay descriptions were combined, if they were combined at all.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Geometric means. A geometric mean is a summary for positive measurements such as antibody titers. In general, it is calculated by transforming measurements to a logarithmic scale, averaging there, and transforming back. This approach is useful when the data are right-skewed or when relative changes are more meaningful than equal absolute changes. The registry names a geometric mean as the primary summary, but does not report the numerical estimate or the detailed calculation procedure.

Confidence intervals. The primary outcome lists a 95% confidence interval. In general, a confidence interval communicates uncertainty in an estimate under the analysis method and its assumptions. A narrower interval indicates greater precision than a wider interval, while neither interval width nor inclusion of a particular value alone establishes clinical importance. Because no primary estimate or interval is reported in the registry record, precision cannot be evaluated for this endpoint.

Antibody-titer assays. The endpoint description distinguishes an assay using egg-propagated influenza virus from one using cell-propagated influenza virus. That distinction identifies different assay material, but the registry record does not report assay-specific numerical results, how the two assay results were handled analytically, or whether one assay was designated as more important. Those details would be needed to interpret any difference between assay results.

Geometric mean increase. The listed secondary outcomes include geometric mean increase for Antigen 2. In general, this kind of summary describes change in antibody titer relative to a baseline measurement, using a geometric rather than arithmetic scale. The registry record does not include the numerical secondary results or specify the exact baseline and calculation details, so no magnitude of increase can be described.

Randomized comparisons. Randomization assigns participants to groups by chance and can reduce systematic differences in baseline characteristics. It does not guarantee identical groups, especially within individual arms, and it does not remove bias from missing data, deviations from assigned treatment, or outcome measurement. The registry identifies the study as randomized but does not report the allocation ratio or sequence-generation procedures. The parallel-group arrangement and listed interventions define distinct groups, but the record does not provide a single comparison that captures every arm.

Masking. The registry labels the trial quadruple-masked and observer-blind. In general, masking can reduce the influence of expectations on participant reports, clinical conduct, and outcome assessment. The record does not explain which people were masked, how masking was maintained, or whether it was assessed. The labels alone therefore do not establish how masking operated in practice.

Analysis population. The primary analysis is described as using the Per Protocol Set, including eligible participants who received the study intervention according to protocol and had immunogenicity results at Day 29, without intercurrent conditions that may interfere with immunogenicity. The available population description ends after referring to prohibited conditions, so the complete criteria are not reported in the registry record. A per-protocol analysis can focus on participants meeting specified study requirements, but excluding participants after randomization can affect comparability if exclusions differ by group or relate to outcomes. The record does not provide the number in the primary analysis set by arm or the criteria applied in full.

Sample-size planning. The registry describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the target effect is a stated fraction of the observed effect. These assumptions describe an illustration rather than the trial’s original design justification. The registry record does not report the study’s own sample-size rationale or establish that the illustrative assumptions governed enrollment. The illustration is not observed power, and its calculations cannot substitute for confidence intervals or reported trial estimates.

Over-dispersion and count data. General statistical context: event counts may vary more than a simple probability model expects, a feature called over-dispersion. If over-dispersion is present, models that assume less variability can understate uncertainty. The posted safety information consists of group-level counts, and the registry record does not report a model-based analysis of these counts or whether over-dispersion was assessed. No inferential safety comparison should be inferred from the descriptive counts alone.

Multiplicity. Testing or estimating many outcomes and group contrasts creates a multiplicity issue: the chance of at least one apparently unusual result can rise when many comparisons are considered. This is general statistical context. The study lists numerous arms and outcome measures, but the statistical plan, hierarchy of outcomes, multiplicity adjustment, and prespecified contrast strategy are not reported in the registry record. In the absence of those details and numerical results, the record does not support claims based on selected comparisons.

10. Multiplicity, Missing Data and Analysis Populations

The study includes multiple candidate interventions, age groups, study parts, antigens, assay descriptions, and outcome measures. The registry lists 56 outcome measures, including primary and secondary immunogenicity outcomes. When many outcomes or comparisons are considered, multiplicity becomes relevant because selective interpretation can make isolated findings appear more persuasive than the full set of evidence warrants. This is general statistical context; it does not establish which comparisons were formally tested in this trial.

The statistical analysis plan, outcome hierarchy, approach to multiplicity, interim analyses, and rules for selecting among candidate doses are not reported in the registry record. It is therefore not possible to determine whether the primary endpoint controlled interpretation of other outcomes, whether comparisons were adjusted, or which analyses were exploratory. The registry identifies the study as dose-finding but does not report the decision criteria used for dose selection.

Missing-data handling is also not reported in the registry record. The primary analysis population is described as the Per Protocol Set, with Day 29 immunogenicity results required for inclusion, but the full inclusion criteria and numbers analyzed by arm are unavailable. The record does not state how missing Day 29 results, protocol deviations, or other exclusions were handled, or whether sensitivity analyses were conducted.

These gaps limit assessment of bias and uncertainty. A per-protocol analysis can differ from an analysis that retains all randomized participants, and the consequences depend on why participants are excluded and whether exclusions vary by group. Without analysis denominators, missing-data methods, and numerical outcome estimates, readers cannot assess how much the analysis population may have influenced the immunogenicity findings.

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 0% 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 bacterial (2.1%), chronic kidney disease (2.1%), lemierre syndrome (2.0%), ophthalmic herpes zoster (2.0%), ulna fracture (2.0%).

The registry reports, for each intervention group, the number of participants at risk and the number affected by serious adverse events, other adverse events, and deaths. The serious-event counts vary across groups; the reported affected counts include 0, 1, 2, and 3. The other-adverse-event counts are also listed by group. Deaths are recorded as 0 in each group. The denominators are not identical across arms, so comparisons should be read with those group-specific totals in mind.

These entries are descriptive participant counts. They do not establish whether an event was caused by vaccination, and the registry record does not provide a causal assessment or a statistical comparison across arms. A count of affected participants is not necessarily the same as a count of distinct event episodes. The record also lists serious-event terms with percentages, including urinary tract infection bacterial and chronic kidney disease at 2.1%, and Lemierre syndrome, ophthalmic herpes zoster, ulna fracture, and atrial flutter at 2.0%. The available information does not specify how those terms map to study arms or provide context for attributing them to an intervention.

Differences in raw counts should not be interpreted as evidence of a difference in risk without considering denominators, event definitions, follow-up, and uncertainty. The registry record does not report those details sufficiently to support a comparative safety conclusion. Zero reported deaths means only that the posted group entries list no deaths; it does not establish the absence of all safety concerns.

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

The registry record establishes that a randomized, masked, parallel-group study evaluated several mRNA-based seasonal influenza vaccine candidates in healthy younger and older adults, with comparator vaccines that differed by study part and age group. It identifies an immunogenicity endpoint based on Antigen 1 antibody geometric mean titer at Day 29 in Part 1 younger adults, and it provides group-level adverse-event counts. These details describe the trial question and some of the posted safety information.

The record does not report numerical primary geometric mean titers or confidence intervals. It therefore does not establish the observed magnitude or precision of the primary antibody response, nor does it permit a numerical comparison with a comparator. Numerical results for the listed secondary immunogenicity outcomes are also not reported in the registry record. No claim about the size, direction, or statistical significance of an antibody difference can be supported by the available outcome information.

An antibody-titer endpoint is a laboratory measure of immune response. In general, it is not interchangeable with a clinical endpoint such as influenza illness, and the registry record does not report a clinical efficacy result. A measured antibody response alone does not establish how well a vaccine prevents illness or how long any response lasts.

The posted safety counts describe events among participants in the listed groups, but they do not by themselves determine causality or comparative risk. The record does not report a complete analysis plan, outcome hierarchy, missing-data methods, or multiplicity procedures. Those omissions, together with absent numerical immunogenicity results, mean that the registry record supports a description of the design and selected safety counts, but not a conclusion about comparative immunogenicity, clinical benefit, or overall safety.

13. Why This Trial Matters Statistically

This trial is statistically notable for its multi-arm structure. It evaluated several mRNA candidates across younger and older adults, and the comparator vaccine differed by part and age group. Such a design can address dose-finding and candidate-selection questions, but the interpretation depends on which contrasts were planned, how outcomes were prioritized, and how multiplicity was handled. Those details are not reported in the registry record.

The study also illustrates the distinction between an overall enrollment and the population used for a particular analysis. Although enrollment is listed as 845, the primary endpoint is described for a Per Protocol Set, while the safety counts have group-specific denominators. Each estimate must be interpreted in relation to its own analysis population rather than assumed to include everyone enrolled.

The chosen primary summary, a geometric mean titer with a confidence interval, is suited to antibody measurements that may be skewed and interpreted on a relative scale. Yet the statistical form of an endpoint cannot replace its numerical estimate. Without the posted titer values and confidence limits, readers cannot judge effect magnitude or precision. This is a useful reminder that endpoint descriptions and trial design information do not alone constitute a report of the estimated treatment effects.

Finally, the registry’s planning illustration is distinct from the trial’s original design justification. The record describes assumptions for an illustration based on an observed effect, but does not report the original sample-size rationale or establish that the illustration governed enrollment. Keeping that distinction clear helps prevent planning calculations from being mistaken for observed evidence or a guarantee of statistical success.

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 registry record does not report numerical results for the primary geometric mean titer endpoint or its 95% confidence interval. It also does not report numerical results for the listed secondary immunogenicity outcomes. This prevents assessment of effect magnitude, precision, and direction for the antibody outcomes that define the study’s stated immunogenicity aims.

The primary endpoint is described for Part 1 younger adults, while the study also included older adults and Part 2 groups. The record does not provide the analysis details needed to understand how results across these populations and parts were intended to inform candidate selection. It does not report dose amounts, even though the study is described as dose-finding, or specify dose-selection criteria.

The Per Protocol Set description is incomplete in the registry record. Numbers included in the primary analysis by arm, details of missing-result handling, and sensitivity analyses are not reported. The allocation ratio, randomization procedures, masking roles, and full statistical analysis plan are also not reported. These gaps limit assessment of potential bias and the reproducibility of the analysis.

The safety information is limited to group-level counts and selected serious-event terms with percentages. The record does not provide a full account of event timing, severity beyond the serious classification, causal assessment, or inferential comparison between groups. The counts should therefore be interpreted descriptively, not as proof that an intervention caused or prevented an event.

Finally, the registry record does not report the original sample-size justification, interim analyses, or multiplicity strategy. The planning assumptions described for an illustration do not fill those gaps. Together, these limitations prevent a complete statistical assessment of the study’s comparative immunogenicity and safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Find the Dose and Assess the Immune Response and Safety of a Vaccine Against Influenza in Healthy Younger and Older Adults — NCT06431607.
• Registry record last updated 2026-03-10; status last verified 2026-02.
• Results first posted 2026-03-10.
• 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

NCT06431607 is a completed Phase 2a randomized, quadruple-masked, parallel-group dose-finding study sponsored by GlaxoSmithKline. It enrolled 845 healthy adults aged 18 years and older, divided into younger- and older-adult groups. The registry lists a study start of 2024-05-23 and primary completion of 2024-12-27.

Participants received single doses of mRNA-based multivalent seasonal influenza vaccine candidates or age- and part-specific comparator vaccines. The primary outcome was the Part 1 younger-adult geometric mean titer of Antigen 1 antibody at Day 29, with a 95% confidence interval, in a Per Protocol Set. The registry describes assays using egg-propagated and cell-propagated influenza virus.

Group-level counts for serious and other adverse events and deaths are posted. Numerical primary and secondary immunogenicity estimates are not reported in the registry record. The statistical analysis plan, missing-data methods, multiplicity strategy, and original sample-size justification are also not reported.