Phase 2 Open-label Study of Alum-adjuvanted Chikungunya Virus-like Particle Vaccine (PXVX0317): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Open-label Study of Alum-adjuvanted Chikungunya Virus-like Particle Vaccine (PXVX0317) (NCT03992872), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With 4-fold Rise in Anti-CHIKV Neutralizing Antibody Response.

2. Clinical Question

This is a comparison of antibody responses between groups with different prior vaccination histories, not a comparison of vaccination with no vaccination: both groups received PXVX0317. The registry describes the naïve group as a control for assessing the effect of pre-existing alphavirus immunity. Because participants were not randomly allocated, any observed group difference would need to be interpreted as an association within this study rather than as a definitive causal effect of prior vaccination. The registry record does not report the primary endpoint results, so the size, direction, and precision of any group difference are not reported in the registry record.

3. Trial Design

This was a Phase 2, open-label, parallel-group study with non-randomized allocation. It enrolled 60 healthy adults aged 18–65 years, with the stated purpose of assessing the safety and immunogenicity of PXVX0317 in prior recipients of other alphavirus vaccines compared with alphavirus-naïve controls. The study is marked completed; the recorded start date is 2019-11-20 and the primary completion date is 2021-01-19.

The registry describes two groups: Prior Alpha and Control: Naïve Alpha. Both groups received the same investigational product according to the same schedule. The control group therefore provides a comparison by prior alphavirus vaccination history, not an untreated or placebo group. The groups were described as age- and gender-matched. The registry record does not report how matching was implemented or whether analyses accounted for the matching.

Open-label means the study was not masked. Non-randomized allocation means participants were not assigned to groups through randomization, so the groups may differ in ways beyond their prior vaccination history. Age and gender matching addresses those specified characteristics as described in the record, but does not establish comparability on other factors. The record does not report further details of recruitment, eligibility criteria beyond the healthy-adult age range, or the allocation process.

The primary outcome was the percentage of participants with a 4-fold or greater rise in anti-CHIKV neutralizing antibody at Day 22 (21 days after vaccination), assessed in the immunogenicity-evaluable population. Secondary outcomes included antibody titers, antibody rises, threshold-based antibody responses, and anti-VEEV neutralizing antibody measures. The registry lists 13 outcome measures and 53 analyses. The statistical analysis plan, including any adjusted comparison, is 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

Analysis population for the primary outcome, as defined in the registry: Immunogenicity evaluable population

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 Percentage of Participants With 4-fold Rise in Anti-CHIKV Neutralizing Antibody Response, measured over Day 22 (21 days after vaccination).

The primary endpoint is the percentage of participants with seroconversion, defined in the record as a 4-fold or greater rise in neutralizing antibody against chikungunya virus. Antibody was measured with a luciferase-based assay, identified as NT80. The assessment time was Day 22 (21 days after vaccination), and the endpoint population was the immunogenicity-evaluable population.

A fold-rise endpoint expresses change relative to a participant’s baseline antibody level. It can therefore capture a response relative to starting level, rather than relying only on the antibody level measured after vaccination. This distinction may matter when comparing groups whose prior alphavirus vaccination histories differ and whose baseline antibody levels could differ. The registry record does not report baseline values or the details of how baseline measurements were handled.

The endpoint is binary at the participant level: each participant either meets the specified rise criterion or does not. The group result is expressed as a percentage. Such a summary is easy to interpret as the proportion meeting the response definition, but it does not show the full distribution of antibody measurements or how far individual responses exceeded the threshold. The secondary outcomes include geometric mean titers and other response summaries that address related aspects of antibody response.

The registry record gives the endpoint definition and assessment time, but not the observed percentages, confidence intervals, or the underlying participant counts for this primary outcome. Its magnitude and precision are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical concepts can clarify what the planned endpoint represents, but the registry record does not report the full statistical analysis plan or the primary endpoint estimates. The explanations below are general and do not imply that a particular analysis was performed unless it is explicitly described in the record.

What does a percentage response measure?

The primary endpoint classifies each participant according to whether the measured anti-CHIKV neutralizing antibody response meets the defined 4-fold-rise criterion. A group percentage summarizes the fraction of evaluated participants meeting that criterion. This is a binary outcome at the participant level, even though the underlying antibody measurement is continuous. The summary is straightforward to communicate, but it discards information about the magnitude of responses among participants who meet the criterion and among those who do not.

Why use a fold-rise definition?

In general, defining response as a fold rise relates the post-vaccination measurement to an earlier measurement from the same participant. This can be useful when baseline levels vary, since an identical post-vaccination level could represent different degrees of change for participants starting at different levels. It does not remove all interpretive concerns: baseline measurement properties, the assay, and the precise analysis population all matter. The record identifies the 4-fold criterion, the NT80 assay, and the immunogenicity-evaluable population, but baseline distributions and detailed handling of measurements are not reported in the registry record.

What does a confidence interval tell the reader?

In general, a confidence interval gives a range of values compatible with the data under the assumptions of the chosen statistical procedure. Its width conveys precision: less precise estimates tend to have wider intervals. A confidence interval is not a guarantee that the true value lies within the displayed range, nor does it by itself establish clinical importance. The primary endpoint lists a 95% confidence interval as its dispersion measure. The actual interval limits are not reported in the registry record, so precision cannot be assessed from the record.

How should the group comparison be understood?

The study used non-randomized allocation and an open-label design. In general, randomization helps balance both measured and unmeasured characteristics across groups, while matching can address selected characteristics. The record describes age- and gender-matched groups, but it does not report the matching procedure, whether matched sets were preserved in the analysis, or whether any covariate adjustment was used. It is therefore not possible to infer the analysis model or its assumptions. Since both groups received PXVX0317, the comparison addresses differences between groups defined by prior alphavirus vaccination history rather than vaccine versus no vaccine.

What are the secondary antibody summaries for?

The listed secondary outcomes include geometric mean titers, 4-fold rises, threshold-based anti-CHIKV antibody measures, and anti-VEEV neutralizing antibody outcomes. In general, geometric means summarize measurements that are positive and often analyzed on a logarithmic scale; they can describe the central tendency of antibody titers differently from a responder percentage. Threshold outcomes indicate whether measurements cross a selected level, while fold-rise outcomes focus on change from baseline. These measures can complement one another, but they answer different questions and should not be treated as interchangeable evidence.

What is over-dispersion, in general?

For binary outcomes, a simple model may assume that variation follows a specified distribution. Over-dispersion means the observed variability is greater than that model expects. If ignored when present, estimated uncertainty may be too small. More flexible methods or robust uncertainty estimates can sometimes address this issue. This is a general statistical consideration, not a description of the trial’s analysis: the registry record does not report whether over-dispersion was assessed or how uncertainty was calculated beyond identifying a 95% confidence interval for the primary endpoint.

What can planning calculations say?

Sample-size calculations are planning illustrations, not observed power. The stated assumptions for the planning illustration are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. For non-time-to-event outcomes, the convention is participants per arm for 80% power; the record also describes a 90% power planning convention. Such calculations depend on assumed effects and model conditions. They do not show the probability that the completed study detected an effect, and they do not replace the observed estimates or their confidence intervals. The planning outputs themselves are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Experimental: Prior Alpha", "Control: Naive Alpha")
n      <- c(30, 30)
events <- c(30, 30)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Experimental: Prior Alpha  30  30  100.0  88.4  100.0  88.6  100.0  88.8  99.9
ARM  Control: Naive Alpha  30  30  100.0  88.4  100.0  88.6  100.0  88.8  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 53 analyses. Multiple outcome measures and analyses create a multiplicity issue: when many statistical questions are examined, the chance of at least one apparently notable result can increase. In general, investigators may address this through a prespecified hierarchy, adjustment procedures, or a clear distinction between confirmatory and exploratory analyses. The registry record does not report whether any such approach was used, how the primary endpoint was prioritized relative to secondary outcomes, or whether the 53 analyses were prespecified.

The record identifies the primary analysis population as the immunogenicity-evaluable population. It does not report the criteria for membership in that population, the number included in the primary analysis, or how participants with missing antibody measurements were handled. Missing-data methods can affect estimates if participants with unavailable results differ from those with observed results. The registry record does not report the amount or pattern of missing primary endpoint data, any imputation approach, or sensitivity analyses.

The registry reports enrollment of 60, but enrollment alone does not identify the analysis denominator for each endpoint. The safety figures list 30 participants at risk in each group; those safety denominators should not be assumed to be the immunogenicity denominators. The record also does not report whether the primary analysis was adjusted for matching or other characteristics. These omissions limit assessment of how the reported endpoint would be calculated and how robust it would be to missingness or analytic choices.

12. 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: pain in extremity (3.3%).

The registry reports serious adverse events for the two groups separately. In Prior Alpha, 0 serious adverse events were reported among 30 participants at risk. In Control: Naïve Alpha, 1 serious adverse event was reported among 30 participants at risk. The record lists pain in extremity at 3.3% among the top serious adverse event terms. It also reports 17 participants with other adverse events in each group and 0 deaths in each group.

These are descriptive counts in a non-randomized, open-label study. A count of 0 does not establish that an event is impossible, and a small number of events cannot characterize rare risks precisely. The single reported serious event does not, by itself, establish whether the event was caused by vaccination. The registry record does not report further details about event timing, severity classification beyond the serious-event category, or the investigator’s assessment of relatedness for that event. The safety figures should be read separately from the immunogenicity endpoint; they do not supply the missing antibody-response results.

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

The study was designed to examine safety and immunogenicity after PXVX0317 in adults with different prior alphavirus vaccination histories. Its primary endpoint asks what percentage of participants had a 4-fold or greater rise in anti-CHIKV neutralizing antibody at Day 22 (21 days after vaccination). The record also describes related antibody outcomes and reports selected safety counts.

What the registry record does not establish is the observed primary response in either group. The primary endpoint percentages, participant counts, confidence intervals, and comparison results are not reported in the registry record. Without those data, the size and precision of the antibody response, and whether the groups differed, cannot be determined from the record.

Even if a group difference were reported, the design would require careful interpretation. Both groups received the same investigational product, and the comparison was based on prior vaccination history rather than random assignment. The age- and gender-matched description addresses those characteristics as stated, but other differences between groups could remain. An observed association would not by itself show that prior alphavirus vaccination caused a difference in the response.

The endpoint is a threshold-based summary. It conveys the proportion meeting the response definition, not the full range of antibody levels or individual changes. Secondary measures such as geometric mean titers and threshold-based outcomes could add context, but their results are also not reported in the registry record. The safety counts describe reported events in the study groups; they do not determine the antibody response or settle causal attribution.

Accordingly, the registry record can be used to understand the question, design, endpoint definition, and reported safety counts. It does not provide enough outcome information to judge the magnitude, precision, or comparative immunogenicity results of this study.

14. Why This Trial Matters Statistically

Statistically, the study is notable for separating participants by prior alphavirus vaccination history while administering the same investigational product to both groups. That design asks whether antibody responses differ across those histories, rather than estimating a vaccine-versus-no-vaccine contrast. The distinction is central to interpreting any group comparison.

The primary outcome is a defined seroconversion percentage at a specified post-vaccination assessment. This makes the question concrete, while also highlighting the value of reporting both the response proportions and their uncertainty. A threshold-based outcome can be readily understood, but it does not describe the full distribution of antibody measurements. The listed secondary measures address complementary features of the response, such as titers and threshold attainment.

The non-randomized, open-label design also illustrates why design features affect statistical interpretation. Matching on age and gender can improve comparability for those characteristics, but matching does not make groups equivalent in all respects. A careful account would therefore need transparent methods for the group comparison and a clear description of the analysis population.

The registry lists 13 outcome measures and 53 analyses, making it important to know how outcomes were prioritized and whether multiplicity was considered. The record does not report those details or the primary endpoint results. Thus, the study’s statistical question is identifiable, but its answer and precision cannot be assessed from the registry record. That distinction between a clearly specified estimand and unavailable results is itself important when evaluating clinical-trial records.

15. 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 contains limited information for evaluating the primary immunogenicity result. It defines the endpoint, assay, assessment time, and analysis population, but does not report the group-specific response percentages, counts, confidence intervals, or test results. The magnitude and precision of the primary finding are therefore not reported in the registry record.

The study is open-label and uses non-randomized allocation. Participants were grouped by prior alphavirus vaccination history, so differences in outcomes could be associated with other group characteristics. The record describes age- and gender-matching but does not report the matching procedure, balance on other characteristics, or any adjustment strategy. It also does not report how the primary comparison handled matching.

Interpretation is further limited by missing detail on the immunogenicity-evaluable population. The criteria for inclusion, endpoint-specific denominators, missing measurements, and handling of missing data are not reported in the registry record. The record lists 13 outcome measures and 53 analyses, but does not describe a multiplicity strategy or identify how secondary analyses were positioned relative to the primary endpoint.

The safety information is also limited to reported counts and a listed serious adverse event term. Further event-level context and attribution are not reported in the registry record. These limitations do not establish that the study was conducted improperly; they describe what cannot be assessed from the information recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2 Open-label Study of Alum-adjuvanted Chikungunya Virus-like Particle Vaccine (PXVX0317) — NCT03992872.
• Registry record last updated 2024-10-16; status last verified 2024-09.
• Results first posted 2024-10-16.
• 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.

19. Record Summary

NCT03992872 is a completed Phase 2, open-label, parallel-group study with non-randomized allocation. It enrolled 60 healthy adults aged 18–65 years and compared prior recipients of experimental alphavirus vaccines with alphavirus-naïve controls. Both groups received PXVX0317 according to the same schedule, and the groups were described as age- and gender-matched.

The primary endpoint was the percentage with a 4-fold or greater rise in anti-CHIKV neutralizing antibody at Day 22 (21 days after vaccination), measured by the luciferase-based NT80 assay in the immunogenicity-evaluable population. The registry lists 13 outcome measures and 53 analyses. The primary endpoint results and statistical analysis plan are not reported in the registry record.

For safety, the record reports 0 serious adverse events in Prior Alpha and 1 in Control: Naïve Alpha, with 30 participants at risk in each group. It reports 17 participants with other adverse events in each group and 0 deaths in each group.