Trial of an Inactivated Yellow Fever Virus Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of an Inactivated Yellow Fever Virus Vaccine (NCT05172544), a randomized phase 1 study. The primary outcome is Occurrence of All Serious Adverse Events (SAEs) at Any Time During the Study.

2. Clinical Question

The central question is about safety, reactogenicity, and tolerability of the vaccine in a Phase 1 study, rather than a clinical efficacy comparison. The primary outcome counts serious adverse events during the specified period. The posted outcome lists 0 serious adverse events for the low-dose group, 0 for the high-dose group, and 0 for placebo.

The registry also lists immunogenicity outcomes: seroconversion, defined as a plaque reduction neutralizing titer (PRNT50) of at least 1:10, and geometric mean neutralizing titers at specified assessment times. These are secondary outcomes. The registry record does not post analysis results for those secondary outcomes, so the primary safety count does not answer whether immune responses differed among groups.

The study description says participants were assigned to the 1 mcg or 5 mcg dose groups or placebo, with sentinel and expanded dosing groups. The posted primary outcome combines the two sentinel and expanded groups into low-dose and high-dose categories. The posted outcome therefore addresses the occurrence of serious adverse events by these broad groups, not a separately reported contrast for each dosing stage.

3. Trial Design

This is a randomized, double-blind, placebo-controlled, parallel-group Phase 1 trial of the inactivated yellow fever virus vaccine HydroVax-002 YFV. The registry lists the trial as completed. Its recorded start date is 2022-01-13 and its primary completion date is 2023-04-24. The registry enrollment is 26; the brief summary describes a plan to enroll up to 25 healthy adults. The registry record does not explain this difference.

The vaccine was administered intramuscularly as a two-dose series on Days 1 and 29. The low dose was 1 mcg and the high dose was 5 mcg. The arm descriptions distinguish sentinel and expanded groups at each dose. For the low-dose sentinel group, the description specifies 3 participants receiving vaccine and 1 receiving placebo; for the low-dose expanded group, 7 receive vaccine and 2 receive placebo. For the high-dose sentinel group, 3 receive vaccine and 1 receives placebo; for the high-dose expanded group, 7 receive vaccine and 1 receives placebo. The posted primary results are presented instead as Low Dose, High Dose, and Placebo.

The primary outcome is the occurrence of all serious adverse events from Day 1 after the first vaccination to Day 180 after the second vaccination. The registry lists 10 participants in the low-dose outcome group, 10 in the high-dose group, and 5 in the placebo group. It notes that 1 placebo participant was excluded from the primary analysis because that participant did not receive vaccination.

The registry identifies randomization and double masking but does not report the randomization sequence method, allocation concealment procedure, or details of how masking was maintained. The brief summary specifies double-blinding within dosing group. The record also describes dose escalation, but the operational rules for escalation or any decisions between dosing groups 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: One placebo subject was excluded from analysis (Did not receive vaccination).

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 Occurrence of All Serious Adverse Events (SAEs) at Any Time During the Study, measured over Day 1 post first vaccination to Day 180 post second vaccination.

The primary endpoint counts serious adverse events occurring from Day 1 after the first vaccination through Day 180 after the second vaccination. In the posted results, the low-dose, high-dose, and placebo groups each have a recorded count of 0. The endpoint is a count, not a measure of symptom severity across all participants or a measure of immune response.

Serious adverse events are used in safety evaluation because they capture events meeting seriousness criteria, which are distinct from expected or less serious reactions. The registry record does not define its criteria for classifying an event as serious. It also does not report the individual event terms for this outcome; the adverse-event record lists no top serious terms.

In general, a count can describe how many events were recorded, while a participant-level risk describes how many participants experienced at least one event over a defined period. These are not interchangeable when a participant could experience more than one event. The posted primary outcome is labeled as a number of serious adverse events. The registry record does not clarify whether repeated events in one participant are counted separately or how event counts were adjudicated.

The endpoint is relevant to the trial's stated primary objective of assessing safety, reactogenicity, and tolerability. However, the serious-event count alone does not capture all aspects of tolerability. The record separately lists other adverse events, but it does not provide detailed event descriptions in the registry record reported for this analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary measure as a count of serious adverse events. The posted values are 0 for Low Dose, 0 for High Dose, and 0 for Placebo. A count endpoint records the number of events under the endpoint definition; it is different from a continuous measure such as a geometric mean titer and different from a binary measure such as whether a participant seroconverted.

What does a zero count tell us?

In general, a zero observed count means no events meeting the recorded endpoint were counted in the analyzed data. It does not mean that the underlying event rate is known to be zero. When samples are limited, uncommon outcomes may not occur during observation even when the underlying probability is not zero. The extent of uncertainty depends on the amount and completeness of observation, the event definition, and the statistical method used. The registry record does not report a confidence interval or a formal model for these counts.

The primary result does not include an inferential comparison. In general, an inferential comparison would specify the quantity being contrasted, such as a difference in event rates, and a method for estimating uncertainty or testing a hypothesis. The record posts group counts but no primary analysis records, p-values, or interval estimates. It is therefore not possible to use the posted information to describe a statistically estimated difference between vaccine and placebo.

Why does the analysis population matter?

The primary outcome description states that 1 placebo participant was excluded because that participant did not receive vaccination. The posted primary-outcome group sizes are 10 for Low Dose, 10 for High Dose, and 5 for Placebo. An analysis population determines which participants contribute to a particular result. In general, excluding participants can change the interpretation of a safety analysis, especially if follow-up or vaccination differs across participants. The registry record does not report whether the primary analysis followed an intention-to-treat, per-protocol, or other named population definition, nor does it describe how incomplete observations were handled.

The record describes randomized assignment, but it does not report the sequence-generation method or allocation concealment. These design details can help readers assess how assignments were generated and protected from foreknowledge. Double masking is reported, with the brief summary specifying masking within dosing group. The record does not describe who was masked, the practical procedures used to preserve masking, or whether masking was assessed.

How should the secondary outcomes be distinguished?

The registry lists two secondary outcomes. One measures the percentage of participants reaching a PRNT50 titer of at least 1:10 at specified times after vaccination. This is a binary outcome at each assessment: a participant either meets the stated threshold or does not. The other outcome measures geometric mean neutralizing titers at specified times. In general, a geometric mean summarizes measurements on a multiplicative scale and is often used for quantities whose distribution is skewed. These outcomes concern immunogenicity and are conceptually distinct from the primary serious-adverse-event count.

The registry lists no analysis records for these secondary outcomes. Their numerical results, uncertainty estimates, analysis populations, and handling of repeated measurements are not reported in the registry record. Thus, the secondary outcome definitions establish what was intended to be assessed, but do not establish what the observed immune responses were.

What can planning calculations establish?

In general, a sample-size calculation describes the amount of information a proposed study might need under specified assumptions. It is not a result observed in the trial and does not determine what the posted data show. The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also specifies that the effect to detect is a stated fraction of the observed effect. For time-to-event illustrations, the total number of events is the planning quantity; for other outcomes, the quantity is participants per arm. These are planning assumptions, not evidence that the trial was designed or powered using those assumptions.

The registry record does not report the trial's own sample-size justification or a statistical analysis plan. It does not report whether interim analyses were planned or performed, the method for controlling multiplicity, or a prespecified approach to missing data. Without these details, the posted outcome should be interpreted descriptively rather than as the result of a fully documented confirmatory testing framework.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and two secondary immunogenicity outcomes. The secondary outcomes involve seroconversion at specified assessment times and geometric mean neutralizing titers at specified assessment times. Considering several outcomes and assessment times can create multiplicity: in general, the more statistical comparisons made, the greater the chance of at least one apparently unusual result arising by chance if each is interpreted separately. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting the secondary outcomes.

No analysis records are listed, and the registry entries reported for the secondary outcomes do not include numerical results. The registry record therefore does not show whether those outcomes were analyzed, whether all planned assessment times were reported, or what inferential procedures were used. The absence of posted results is not itself evidence that the outcomes had no effect.

For the primary endpoint, the record states that 1 placebo participant was excluded because that participant did not receive vaccination. The analysis population is therefore not described simply as all randomized participants. The registry record does not report how any other missing observations, withdrawals, or incomplete follow-up were handled. It also does not specify whether event follow-up was complete for every participant through Day 180 after the second vaccination.

In general, missing-data methods matter because conclusions may depend on whether information is missing and why it is missing. No assumptions or sensitivity analyses for missing data are reported in the registry record. The record also does not report a statistical analysis plan, so it is not possible to determine from the posted information whether the analysis population and missing-data methods were prespecified.

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 serious adverse event counts are 0 in Low Dose, 0 in High Dose, and 0 in Placebo. The corresponding group sizes listed for this endpoint are 10, 10, and 5. The stated window is Day 1 after the first vaccination through Day 180 after the second vaccination. The record notes that 1 placebo participant was excluded from analysis because that participant did not receive vaccination.

These are counts, not percentages or risk estimates. No percentages, confidence intervals, or between-group tests are reported for this endpoint in the registry record. In general, a zero count in a small study does not demonstrate that an event cannot occur or provide a precise estimate of its frequency. It describes what was recorded in the analyzed participants during the stated observation window.

The separate adverse-event record lists 0 serious events and other adverse events affecting 6 participants in Low Dose, 7 in High Dose, and 5 in Placebo. Those other-event counts should not be read as serious events. The registry record does not provide the terms, severity, timing, or attribution of those other adverse events in the registry record. The serious-event result is therefore one part of the safety record, not a complete description of all tolerability findings.

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

The posted primary result means that no serious adverse events were recorded in the Low Dose, High Dose, or Placebo groups for the specified follow-up period. It is a descriptive result in a randomized, placebo-controlled Phase 1 study of HydroVax-002 YFV. It does not by itself establish that the vaccine is safe, establish equivalence between groups, or rule out uncommon serious events.

The group sizes listed for the primary endpoint are 10 for Low Dose, 10 for High Dose, and 5 for Placebo. Such observations provide limited information about uncommon outcomes, particularly when the event count is zero. The registry record does not report confidence intervals or a statistical comparison, so the precision of any difference between groups is not quantified. There is also no posted analysis result for the secondary seroconversion or neutralizing-titer outcomes in the registry record.

The result does not show whether the vaccine prevents yellow fever or how well it might work in a broader population. The primary endpoint is safety-related, and the listed secondary outcomes address immune responses rather than clinical disease prevention. The registry record does not include a clinical efficacy endpoint in the registry record reported for this analysis.

Nor does the result describe every aspect of safety. Other adverse events are listed separately, and their event terms and clinical details are not reported in the record summarized by these registry entries. The primary endpoint's seriousness criteria and event-adjudication procedures are also not described.

The appropriate statistical reading is narrow: the posted serious-event count is zero in each of the three reported groups over the defined window, with no inferential analysis reported. Broader conclusions would require information that is not reported in the registry record, including complete outcome detail, uncertainty estimates, and analysis methods.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between observing no events and establishing that an event is absent. The posted serious adverse event counts are 0 in all three groups. Those counts communicate what occurred in the analyzed data, but without uncertainty estimates they do not show how precisely the underlying safety experience has been characterized.

The trial also illustrates the importance of matching interpretation to endpoint type. Its primary endpoint is an event count over a defined follow-up period, while its secondary outcomes concern a threshold-based seroconversion measure and geometric mean neutralizing titers. Those outcomes answer different questions and require different summaries. A zero serious-event count cannot stand in for an immunogenicity analysis, and an immune-response measure would not by itself establish clinical efficacy.

Group definition also matters. The study description distinguishes low- and high-dose sentinel and expanded groups, while the posted primary results report Low Dose, High Dose, and Placebo. The registry record notes a placebo exclusion from the primary analysis because the participant did not receive vaccination. These details show why readers need both the endpoint definition and the analysis-population description to understand what each result represents.

Finally, the record lists no analysis records and does not report the statistical analysis plan, missing-data procedures, or multiplicity approach. This makes it important to distinguish descriptive registry results from a prespecified confirmatory analysis. The statistical value of the result lies in its transparent, limited description—not in supporting conclusions beyond what the recorded outcome and its precision can 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 registry record does not provide confidence intervals, hypothesis tests, or a formal comparison for the primary serious-adverse-event count. It therefore does not quantify uncertainty around the observed zero counts or estimate the difference between vaccine and placebo groups. The record also does not report a protocol-based sample-size justification, so the reason for the enrollment target and its suitability for assessing safety are not available.

The record states that 1 placebo participant was excluded because that participant did not receive vaccination. It does not report a full analysis-population definition, the number or handling of any other missing observations, or the completeness of follow-up through Day 180 after the second vaccination. The posted group sizes alone do not establish whether all participants contributed complete safety observation over the whole period.

The endpoint description does not specify the criteria used to classify serious adverse events, how events were collected or adjudicated, or how multiple events in one participant were represented in the count. The adverse-event details also do not provide event terms or details for the other adverse events.

The registry record identifies randomization and double masking but does not report the sequence-generation method, allocation concealment, or detailed masking procedures. It does not report an analysis plan, interim-monitoring methods, or multiplicity procedures. Although two secondary immunogenicity outcomes are listed, their numerical results are not included in the registry record. These gaps limit interpretation of both the safety result and the planned secondary assessments.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial of an Inactivated Yellow Fever Virus Vaccine — NCT05172544.
• Registry record last updated 2025-09-18; status last verified 2025-09.
• Results first posted 2024-05-16.
• 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 NCT05172544, a completed randomized, double-blind, placebo-controlled, parallel-group Phase 1 trial of HydroVax-002 YFV in healthy adults. It lists an enrollment of 26 and records a start date of 2022-01-13 and primary completion date of 2023-04-24. The vaccine was given intramuscularly on Days 1 and 29 at 1 mcg or 5 mcg, with placebo as comparator.

The primary outcome is the number of serious adverse events from Day 1 after the first vaccination to Day 180 after the second vaccination. The posted counts are 0 for Low Dose, 0 for High Dose, and 0 for Placebo. The registry notes that 1 placebo participant was excluded from this analysis because that participant did not receive vaccination.

Two secondary immunogenicity outcomes are listed, but no analysis records are posted. Confidence intervals, inferential tests, the trial's statistical analysis plan, and the sample-size justification are not reported in the registry record.