Safety and Immunogenicity of Three V181 Dengue Vaccine Potencies in Adults (V181-003): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of Three V181 Dengue Vaccine Potencies in Adults (V181-003) (NCT05507450), a randomized phase 2 study. The primary outcome is Dengue Virus-Neutralizing Antibody Titers, as Measured by Virus Reduction Neutralization Test (VRNT).

2. Clinical Question

The question concerns an immune-response measurement rather than reported dengue disease cases. The trial also evaluates safety and tolerability across three vaccine potency levels. The registry record states the intended non-inferiority hypothesis, but does not report the antibody estimates, confidence intervals, or a non-inferiority margin. It therefore does not provide enough statistical evidence to determine whether the primary hypothesis was met.

3. Trial Design

This is a phase 2, randomized, double-blind, multicenter, parallel-group study of V181 dengue vaccine potency levels in healthy adults. The registry reports enrollment of 1271 and a completed study. The recorded study start was 2022-09-07, and primary completion was 2023-06-05.

Participants were assigned to V181 High-Potency Level, V181 Mid-Potency Level, V181 Low-Potency Level, or placebo. Each group description specifies a single subcutaneous dose of 0.5mL. The primary objective is narrower than the full set of study groups: it compares low-potency with mid-potency for neutralizing antibody geometric mean titers at Day 28 after vaccination. The high-potency and placebo groups are part of the study, but are not named as the primary comparison groups.

Random allocation is intended to make treatment groups comparable, on average, with respect to factors that could affect outcomes. Double blinding is intended to limit the influence of treatment knowledge on participant experience, clinical assessment, and reporting. These are general design purposes; the registry does not describe the practical masking procedures or allocation method.

The primary immunogenicity population is defined as randomized participants without protocol deviations judged capable of substantially affecting the analysis. The registry specifically identifies baseline seropositivity assessed by VRNT and missing serology results as examples of such deviations. The full eligibility criteria, group-specific immunogenicity analysis counts, and details of the allocation process are not reported in the registry 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 population analyzed was all randomized participants without protocol deviations that could have substantially impacted the results of the immunogenicity analyses. These deviations include participant was seropositive at baseline as assessed by VRNT and missing serology results.

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.

6. Primary Endpoint

The registry lists the primary outcome as Dengue Virus-Neutralizing Antibody Titers, as Measured by Virus Reduction Neutralization Test (VRNT), measured over Day 28 post-vaccination.

The primary endpoint is dengue virus-neutralizing antibody titer, assessed by a virus reduction neutralization test (VRNT). The reported summary measure is the geometric mean titer (GMT) for each of four serotypes: DENV1, DENV2, DENV3, and DENV4. Specimens were collected at Day 28 post-vaccination.

A neutralizing antibody assay measures the capacity of antibodies in a specimen to inhibit virus in the test system. A GMT summarizes titers across participants using a geometric rather than arithmetic average. As a general statistical explanation, antibody titers commonly have a skewed distribution; analyzing values on a logarithmic scale and expressing the result as a geometric mean can make group summaries more appropriate for such data. The registry names the GMT but does not report the detailed calculation or analysis procedure.

Confidence intervals describe uncertainty around an estimate under the assumptions of the analysis. The registry lists 95% confidence intervals as the dispersion measure, but does not report the endpoint values or intervals. Thus, the endpoint and measurement time are specified, while the posted registry record does not provide the numerical immunogenicity results needed to assess the size or precision of the comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-blind, parallel-group trial. These design features help define how group comparisons should be interpreted, but they do not reveal the numerical results or the full analysis plan.

What does randomization contribute?

In general, randomization assigns participants to groups by a chance-based process. It aims to balance both measured and unmeasured participant characteristics across groups, reducing the risk that a group difference is simply due to systematic differences present before treatment. Randomization does not guarantee that every characteristic will be identical across groups, especially in any one trial. The registry confirms random allocation but does not describe the sequence-generation method, concealment procedures, or any stratification factors.

Why does blinding matter?

In general, blinding can reduce bias when participants or study personnel know which intervention was assigned. Knowledge of assignment may influence symptom reporting, clinical judgments, or decisions about recording events. The record identifies the study as double-blind but does not specify which roles were masked, how masking was maintained, or whether it was assessed. These implementation details are not reported in the registry record.

What does a geometric mean titer represent?

The primary endpoint summarizes neutralizing antibody titers using a geometric mean for each serotype. In general, a geometric mean is calculated by averaging logarithmically transformed positive values and converting the result back to the original scale. This approach is useful when values vary multiplicatively or are skewed, as titers often can be. It describes a typical level on a multiplicative scale; it is not the same as the arithmetic average. The registry does not state how values below assay limits were handled, how titers were transformed, or which statistical model was used.

The assay is identified as VRNT, and specimens were collected at Day 28 post-vaccination. In general, neutralization assays estimate antibody activity in a controlled laboratory system. They measure an immune response, not the frequency of dengue illness in the trial. The registry does not report assay validation details, laboratory procedures, or the exact unit conventions beyond identifying the endpoint unit as titer.

How should the confidence interval be read?

In general, a confidence interval represents uncertainty in an estimate under a specified statistical model and sampling process. A narrower interval indicates greater precision than a wider interval, while the interval’s location indicates which values are compatible with the data under that method. The registry names 95% confidence intervals for the GMT endpoint, but numerical intervals are not reported. Therefore, neither precision nor the range of plausible group responses can be evaluated from the posted record.

What is the role of non-inferiority?

A non-inferiority study asks whether a treatment’s outcome is not unacceptably worse than that of a comparator, according to a prespecified margin. In general, the margin must be chosen before results are known and justified for the endpoint and clinical context. A conclusion depends on both the estimated contrast and its confidence interval relative to that margin; a nonsignificant superiority test alone would not establish non-inferiority. The registry states the low-potency versus mid-potency non-inferiority objective but does not report the margin, the contrast definition, or the decision rule. It also does not report the test or model used for the comparison.

Why do the analysis population and missing observations matter?

The stated primary population comprises randomized participants without protocol deviations considered likely to substantially affect immunogenicity results. The registry names baseline seropositivity by VRNT and missing serology as examples. In general, excluding participants after randomization can change the composition of the analyzed groups and can affect interpretation, particularly if exclusions differ by group or are related to outcome. The registry does not report group-specific exclusions, the number with evaluable specimens, or a sensitivity analysis using a different population. How missing measurements were handled beyond their inclusion among the stated exclusion examples is not reported.

The registry also lists secondary outcomes concerning solicited injection-site and systemic adverse events. Such outcomes are generally summarized as participant counts or proportions over a defined observation period. The period, statistical comparisons, and analysis procedures for those outcomes are not specified in the information recorded.

No statistical analysis entries are reported in the registry record. Consequently, the detailed modeling approach, assumptions, handling of assay limits, covariate adjustment, multiplicity procedure, and analysis software are not reported. The endpoint description and trial design establish what was intended to be measured, but they do not fill in those methodological details.

10. Multiplicity, Missing Data and Analysis Populations

The primary immunogenicity question covers four serotypes: DENV1, DENV2, DENV3, and DENV4. Testing or estimating effects across several outcomes raises a general multiplicity issue: the chance of at least one misleading result can increase when many claims are assessed. Methods such as a prespecified hierarchy or statistical adjustment can control how evidence is interpreted across outcomes. The registry record does not report whether such a method was planned or used, or how success across the four serotypes was defined.

The registry identifies secondary outcomes for solicited injection-site and systemic adverse events. It does not report a multiplicity strategy linking these secondary outcomes with the primary objective. No statistical analysis entries are reported, so the analysis hierarchy and inferential procedures are not available in the registry record.

The primary analysis population excludes randomized participants with protocol deviations judged capable of substantially affecting immunogenicity analysis. The record gives baseline seropositivity by VRNT and missing serology results as examples. This defines an important part of the intended population, but does not state how many participants were excluded from each group or how missing measurements were otherwise handled. It does not report imputation, sensitivity analyses, or a comparison of results across analysis populations.

These details matter because multiplicity affects the interpretation of evidence across several outcomes, while exclusions and missing observations can affect which participants contribute to an estimate. Without the analysis plan and numerical endpoint results, the registry record does not support an assessment of either issue’s impact on the primary conclusion.

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: tooth impacted (0.9%), diverticulitis (0.9%), perineal abscess (0.9%), scrotal abscess (0.9%), chondromalacia (0.9%).

The registry reports serious adverse events for each study group. The recorded figures are 8 affected participants among 231 at risk in the V181 High-Potency Level group, 9 among 461 in the V181 Mid-Potency Level group, 12 among 459 in the V181 Low-Potency Level group, and 6 among 115 in the placebo group. These are group-specific counts and denominators as recorded; they should not be treated as evidence of a causal relationship to the assigned intervention.

The registry records 0 deaths in the high-potency group, 0 in the mid-potency group, 1 in the low-potency group, and 0 in the placebo group. It does not report a causal attribution for the death. The record also lists serious-event terms, each with 0.9%: Tooth impacted, Diverticulitis, Perineal abscess, Scrotal abscess, Chondromalacia, and Neuroendocrine tumour. It does not provide enough detail in this listing to connect each term to a particular group or to establish relatedness.

In general, adverse-event counts describe events recorded during the study and require context about definitions, follow-up, severity, and attribution. The registry record does not report a formal between-group safety analysis in the information. The figures should therefore be read descriptively rather than as proof that an intervention caused, prevented, or changed an event.

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

The record establishes that this phase 2 study was designed to compare dengue-neutralizing antibody GMTs after V181 vaccination, with a primary non-inferiority question comparing low-potency with mid-potency at Day 28 for four serotypes. It also records a safety and tolerability objective and includes high-potency and placebo groups. These design details identify the questions under study; they do not supply their answers.

The numerical primary endpoint results are not reported in the registry record. There are no posted GMT estimates or confidence intervals in the information recorded here, and the non-inferiority margin and statistical decision procedure are also not reported. It is therefore not possible to conclude whether low-potency met the stated non-inferiority hypothesis, how large any response difference was, or how precisely the response was estimated.

The endpoint is an antibody response measured by VRNT, not a reported count of dengue disease cases. The record does not report a clinical disease endpoint or establish how the measured immune response relates to clinical protection. This distinction is important: a laboratory immune measurement answers a different question from whether participants experienced disease.

The safety counts can be described as registry-recorded events in the respective groups, but the counts alone do not establish causation or comparative safety. The record does not provide a formal safety analysis, event attribution, or enough detail to interpret the listed serious-event terms as treatment-related.

Accordingly, the registry supports a careful account of the study design, endpoint, analysis population description, and recorded safety counts. It does not support a claim that one potency level produced a greater, equivalent, or acceptably similar antibody response, nor does it establish a clinical benefit or a causal safety effect.

13. Why This Trial Matters Statistically

This study raises a useful statistical question about comparing different vaccine potency levels using a prespecified immune-response endpoint. The primary objective is not simply to ask whether the group averages differ. It frames the comparison as non-inferiority: whether the low-potency response can be judged not unacceptably worse than the mid-potency response for each dengue serotype. That requires a clear margin and an estimate precise enough to assess the margin, not just a point estimate.

Considering four serotypes makes the interpretation more demanding than a single-outcome comparison. Each serotype has a separate GMT, and evidence across them needs a stated rule for how the overall primary objective is judged. Multiplicity methods and a transparent decision rule help avoid overstating a result based on only a subset of outcomes. Those procedures are not reported in the registry record.

The study also illustrates why endpoint definitions and analysis populations matter. The registry identifies a specific assay and Day 28 collection time, and defines an immunogenicity population that excludes certain protocol deviations. Those choices determine which measurements are summarized and which participants contribute. Reporting the resulting estimates, intervals, exclusions, and sensitivity analyses would help readers assess both the result and its robustness.

Finally, immunogenicity and safety answer distinct questions. Antibody titers characterize a laboratory-measured immune response, while adverse-event summaries describe recorded harms during study follow-up. Neither type of result should be treated as a substitute for the other. The record’s objectives make these distinctions statistically important, although the missing primary results and analysis details prevent evaluation of the trial’s conclusions.

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 GMT endpoint. It also does not report the 95% confidence intervals, the between-group contrast, the non-inferiority margin, or the statistical decision rule. These omissions prevent assessment of effect size, precision, or whether the primary objective was met.

The record identifies the primary analysis population and gives examples of protocol deviations that could lead to exclusion, including baseline seropositivity by VRNT and missing serology. It does not report the number analyzed in each group, the number excluded, or whether results were checked in other analysis populations. The approach to missing measurements and assay values outside measurable limits is not reported.

The primary objective involves four serotypes, but the registry does not report a multiplicity procedure or how success across serotypes was defined. The statistical analysis plan, model, test, covariate use, and sample-size justification are not reported in the registry record. These details are especially relevant to interpreting a non-inferiority claim.

The safety record provides counts and selected serious-event terms, but does not report attribution, a formal comparison, or sufficient detail to assess event timing and follow-up in this account. The eligibility criteria, participant characteristics, and full masking procedures are also not reported. These limitations concern the information available in the registry record and should not be taken as evidence that the study did not collect such information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of Three V181 Dengue Vaccine Potencies in Adults (V181-003) — NCT05507450.
• Registry record last updated 2025-05-09; status last verified 2025-04.
• Results first posted 2025-05-09.
• 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

NCT05507450 is a completed, randomized, double-blind, multicenter, parallel-group phase 2 study of V181 potency levels in healthy adults. The registry records enrollment of 1271 and describes groups receiving high-, mid-, or low-potency V181, or placebo, as single subcutaneous doses.

The primary endpoint is VRNT-measured dengue-neutralizing antibody GMT for DENV1, DENV2, DENV3, and DENV4 at Day 28 post-vaccination. The primary objective compares low- with mid-potency and states a non-inferiority hypothesis. The analysis population excludes certain protocol deviations, including baseline seropositivity and missing serology.

Numerical immunogenicity results, the non-inferiority margin, and the detailed statistical analysis plan are not reported in the registry record. Serious adverse-event counts and death counts are recorded by group, but the listed information does not establish causation.