Study Describing the Immunogenicity and Safety of Quadrivalent Recombinant Influenza Vaccine (RIV4) Versus a Licensed Quadrivalent-inactivated Influenza Vaccine (IIV4) (Fluarix® Quadrivalent) in Participants 18 Years of Age and Older in South Korea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Describing the Immunogenicity and Safety of Quadrivalent Recombinant Influenza Vaccine (RIV4) Versus a Licensed Quadrivalent-inactivated Influenza Vaccine (IIV4) (Fluarix® Quadrivalent) in Participants 18 Years of Age and Older in South Korea (NCT05144945), a randomized phase 3 study. The primary outcome is Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 1- Per Protocol Analysis Set (PPAS).

2. Clinical Question

3. Trial Design

This was a Phase III, randomized, parallel-group, active-controlled, multicenter study in South Korea. The registry records quadruple masking. Participants were assigned to receive RIV4 or IIV4, with each group receiving a single intramuscular injection of 0.5 mL on Day 1. The study was completed. Its recorded start date was 2021-12-07, and its primary completion date was 2022-09-01.

The registry reports enrollment of 301 participants and identifies the condition as influenza in healthy volunteers. The planned age description includes adults aged 18 years and older, with objectives to describe antibody responses separately for ages 18–49 and at least 50. The comparator was an active vaccine, not placebo or no vaccination. Random allocation and an active control allow a direct comparison within the trial design, but design features alone do not show the size or precision of any treatment-group difference.

The primary endpoint is specified at Day 1 before vaccination, whereas the study summary describes objectives concerning immune response induced by the vaccines. The record does not provide post-vaccination GMT values or a follow-up timeframe for the primary immunogenicity result. The analysis population for the stated primary measure is the per-protocol analysis set: randomized participants who received a dose and had a post-vaccination blood sample, excluding participants with protocol deviations. The exact number included in that set is not reported in the registry record.

The registry lists 17 outcome measures but 0 analyses. It does not report the detailed allocation procedure, masking implementation, vaccine-strain composition, or statistical analysis plan. These details should not be inferred from the phase, randomization, or masking labels.

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 301 participants were enrolled and randomized in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on PPAS population that included all randomized participants who received a dose of the study vaccine and had a post-vaccination blood sample. Participants with protocol deviations were excluded from the PPAS.

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: Analysis was performed on all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 1- Per Protocol Analysis Set (PPAS), measured over Day 1 (pre-vaccination).

The primary endpoint is the geometric mean titer (GMT) of anti-influenza antibodies measured with a hemagglutination inhibition (HAI) assay. The assay covers 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. Titers are expressed as 1/dilution. The specified measurement is at Day 1 before vaccination, in the per-protocol analysis set, and the registry describes a 95% confidence interval for the GMT.

A GMT summarizes antibody titers using a geometric rather than an arithmetic average. In general, this approach is useful for titer measurements that vary multiplicatively: the values are analyzed on a logarithmic scale and then expressed back on the original scale. The confidence interval conveys uncertainty around the estimated GMT; it is not a range containing every participant’s titer and does not, by itself, test a difference between vaccine groups.

The endpoint’s timing matters for interpretation. A pre-vaccination measurement describes antibody levels at baseline, not the immune response after vaccination. Although the study objectives refer to describing immune response, post-vaccination endpoint values and change-from-baseline results are not reported in the registry record. The posted information therefore defines the assay and measurement but does not provide the numerical primary outcome needed to assess the observed antibody levels or their precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean titer represent?

HAI titers are dilution-based measurements. A geometric mean is appropriate for values that are naturally interpreted through multiplicative changes. In general, calculation proceeds by transforming titers to a logarithmic scale, averaging on that scale, and transforming the average back to the original scale. The result is a summary of the group’s typical titer on the original measurement scale; it is not the arithmetic average and does not describe how widely individual values vary. The registry states that titers are expressed as 1/dilution and that the GMT is reported with a 95% confidence interval.

The confidence interval expresses uncertainty in an estimated group GMT. A narrower interval indicates greater precision for that estimate, while a wider interval indicates less precision. It does not show the full spread of participant-level measurements, and an interval around a group GMT should not be interpreted as an interval for a difference between groups. The registry record does not report the actual GMT estimates or their confidence limits.

What does the HAI endpoint measure?

The HAI assay measures antibodies directed against the influenza strains specified in the registry: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata lineages. An assay result is a laboratory measure of antibody titer, not a direct count of infections or a clinical outcome. The registered primary measure is explicitly at Day 1 before vaccination. That baseline timing must be kept distinct from a later antibody measurement or a change from baseline. Neither post-vaccination GMT results nor change estimates are reported in the registry record.

How should randomization and masking be understood?

Randomization assigns participants to study groups by chance and is intended to reduce systematic differences between groups at entry. Quadruple masking indicates that the registry classifies the study as masked at four role categories, but the record does not identify those roles or explain how masking was maintained. A parallel-group design means participants were assigned to a study group for comparison rather than crossing from one vaccine to the other. These design features can support a fair comparison, but they do not substitute for reported outcome estimates or analysis methods.

The trial was active-controlled: the RIV4 group was compared with an IIV4 group. This makes the question a comparison of the two vaccine groups under the study conditions, not a comparison against no vaccine. The registry describes the study as Phase III and multicenter but does not report the number or locations of participating centers beyond South Korea.

What does the per-protocol analysis set imply?

The primary endpoint description defines the analysis population as randomized participants who received a study-vaccine dose and had a post-vaccination blood sample, with participants who had protocol deviations excluded. Such a per-protocol population is narrower than all enrolled participants and can differ from an analysis that retains everyone as randomized. The registry does not report the number included, the protocol deviations that occurred, or the rules used to classify deviations. It also does not report how missing blood samples or other missing endpoint observations were handled. Consequently, the potential effect of these exclusions on the estimates cannot be assessed from the record.

What can be inferred from the planning assumptions?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. For those illustrations, the effect to detect is described as a stated fraction of the observed effect; participant counts are expressed per arm except for time-to-event settings. These are planning assumptions, not observed results and not observed power. The record does not report the trial’s own sample-size justification or enough outcome estimates to interpret a particular planning illustration as evidence of precision or efficacy.

Over-dispersion is a general statistical concern when outcome variability exceeds what a model assumes. When that occurs, standard errors can be too small and confidence intervals too narrow unless the analysis accounts for the extra variability. That concept does not establish that over-dispersion occurred in this trial: the registry does not describe a model for the primary endpoint or report diagnostic checks. More broadly, the absence of listed analyses means the registry does not identify the exact estimation procedure, adjustment approach, or inferential test used for the posted outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint covers antibody GMTs for 4 influenza strains, and the study objectives also distinguish ages 18–49 from participants aged at least 50. Considering several strains, age groups, outcomes, or time points can create multiplicity: when multiple statistical questions are tested, the chance of at least one apparently notable result may increase. In general, a prespecified multiplicity strategy can control how results are interpreted across a family of comparisons. The registry record does not report such a strategy, a hierarchy among outcomes, or an adjustment method.

The registry lists 17 outcome measures and 0 analyses. It does not provide the numerical immunogenicity results, a complete analysis plan, or details of any subgroup comparisons. It is therefore not possible to determine which comparisons were treated as primary for inference or whether any multiplicity adjustment was applied. The study’s descriptive objectives should not be recast as formal confirmatory tests without those details.

Missing-data handling is also not reported in the registry record. The primary population definition requires a post-vaccination blood sample and excludes protocol deviations, but the record does not state how participants without a sample were handled, how many were excluded, or whether any sensitivity analysis was conducted. The number eligible for the per-protocol analysis is not reported.

The registry does not report an interim-analysis plan, stopping rules, or a trial-specific sample-size justification. Planning illustrations based on an observed effect are not a substitute for those design details and do not represent observed power. These omissions limit assessment of the statistical plan and the robustness of any unreported immunogenicity comparison.

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 non-serious adverse event terms

The registry lists 149 participants at risk in the RIV4 group and 151 in the IIV4 group for the serious adverse-event count. The number listed as affected was 0 in each group. Deaths were also reported as 0 in both groups. No serious-event terms are listed. These entries describe the posted counts; they do not establish that no adverse events of any kind occurred.

For the other adverse-event category, 96 participants were listed as affected among 149 at risk in the RIV4 group, and 100 among 151 at risk in the IIV4 group. These are participant counts, not rates calculated for comparison. The registry record does not report event-level descriptions, severity, duration, relatedness assessments, or the observation period used for these counts. It also does not provide confidence intervals or statistical tests for the safety outcomes.

Safety interpretation should distinguish the serious-event category from the other adverse-event category and should retain the reported denominators. The counts alone do not describe the nature or clinical importance of events, nor do they support a conclusion about comparative safety. Safety follow-up details and the rules defining each category are not reported in the registry record.

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

The record establishes that a Phase III randomized study compared RIV4 with an active IIV4 control in adults aged 18 years and older in South Korea. It describes a pre-vaccination HAI GMT endpoint for 4 influenza strains, a per-protocol population definition, and safety counts for both groups. Those details help identify the intended scientific question and the scope of the posted information.

The record does not report the GMT values, 95% confidence intervals, post-vaccination results, or a between-group immunogenicity estimate. It therefore cannot show the size or precision of the antibody response after vaccination, whether the groups differed, or how an observed difference should be interpreted. A baseline measure before dosing cannot stand in for a post-vaccination response. The stated study objectives and design do not fill this results gap.

The safety entries report 0 serious adverse events and 0 deaths in each group, alongside affected-participant counts in the other adverse-event category. These counts are informative as registry entries but do not, on their own, characterize event type, severity, duration, or comparative risk. The absence of a reported serious event in these counts is not the same as a complete account of all safety outcomes or all possible harms.

More generally, a trial result is interpreted through its estimates, uncertainty, analysis population, and prespecified methods. Here, the registry gives limited analysis detail and lists no analyses. It does not report multiplicity handling, missing-data methods, or the trial’s own sample-size justification. Conclusions should therefore remain within the limits of the design and counts that are actually reported, without treating an unreported immunogenicity comparison as either favorable or unfavorable.

13. Why This Trial Matters Statistically

This trial is statistically relevant because its registry record combines a randomized active-controlled design with an antibody endpoint measured by HAI. The endpoint definition illustrates why outcome timing matters: a baseline GMT and a post-vaccination GMT answer different questions. A pre-vaccination value describes titers before the assigned injection, while an induced response requires results collected after vaccination and an appropriate comparison or change measure.

The record also makes the analysis population explicit. Requiring receipt of a dose and a post-vaccination blood sample, while excluding protocol deviations, defines a per-protocol set that is not automatically identical to the full randomized population. Readers need the population size, exclusions, and missing-data procedures to judge how representative that analysis is and whether selection could affect interpretation. Those details are not reported in the registry record.

Several strains and age groups are part of the stated objectives. This creates an important statistical distinction between describing multiple outcomes and making formal claims across them. Without reported analysis methods or multiplicity handling, the strength of any hypothetical finding across strains or age groups could not be assessed. In this record, numerical immunogenicity findings and analyses are absent, so the distinction remains a limitation rather than a basis for a comparative conclusion.

Finally, the safety information illustrates the difference between counts and a full comparative assessment. The record provides affected-participant counts and denominators, but not event details, uncertainty estimates, or an analysis plan. The study’s randomized design is important context, but design quality cannot compensate for unreported estimates or methods when assessing what the posted results establish.

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 central limitation is that the registry record does not report the primary immunogenicity estimates or their 95% confidence intervals. It identifies the primary endpoint as Day 1 pre-vaccination GMTs, but does not give values for the 4 strains, post-vaccination results, or a between-group comparison. Thus the stated immune-response objective cannot be evaluated from the posted numerical results.

The primary endpoint timing also limits interpretation: the specified Day 1 measurement precedes vaccination. The record does not explain how the listed baseline measure relates to the later immune-response objective. Follow-up timing for immunogenicity and safety is not reported in the registry record.

The per-protocol population requires a dose and a post-vaccination blood sample, and excludes participants with protocol deviations. Its size, the number and nature of exclusions, and the handling of missing observations are not reported. The record also does not provide the detailed statistical analysis plan, multiplicity methods, interim-analysis information, or trial-specific sample-size justification. Although planning illustrations are described, they are not observed-power calculations or evidence of a trial result.

Safety information is limited to affected-participant counts and denominators, serious adverse-event counts, and deaths. Event descriptions, severity, duration, relatedness, observation time, and comparative uncertainty are not reported. The registry lists 301 enrolled participants, while the reported safety denominators are 149 and 151; the size of the per-protocol population is not given. These populations should not be assumed to be interchangeable.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Describing the Immunogenicity and Safety of Quadrivalent Recombinant Influenza Vaccine (RIV4) Versus a Licensed Quadrivalent-inactivated Influenza Vaccine (IIV4) (Fluarix® Quadrivalent) in Participants 18 Years of Age and Older in South Korea — NCT05144945.
• Registry record last updated 2025-09-11; status last verified 2025-09.
• Results first posted 2023-09-29.
• 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

NCT05144945 is a completed Phase III randomized, quadruple-masked, parallel-group, active-controlled multicenter study in South Korea. It enrolled 301 participants aged 18 years and older and compared a single 0.5 mL intramuscular dose of RIV4 with a single 0.5 mL intramuscular dose of IIV4 on Day 1. The study dates recorded are 2021-12-07 for start and 2022-09-01 for primary completion.

The primary measure is HAI GMT for antibodies against 4 influenza strains at Day 1 before vaccination, in a per-protocol analysis set. The registry lists 17 outcome measures and 0 analyses but does not report numerical immunogenicity results or a between-group estimate. Serious adverse events and deaths are listed as 0 in both groups; other adverse-event affected-participant counts are 96 of 149 for RIV4 and 100 of 151 for IIV4. Further safety detail and key statistical methods are not reported in the registry record.