A Phase 3 Trial of the VLP-Based Chikungunya Vaccine PXVX0317 (CHIKV VLP Vaccine): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 3 Trial of the VLP-Based Chikungunya Vaccine PXVX0317 (CHIKV VLP Vaccine) (NCT05072080), a randomized phase 3 study. The primary outcome is Incidence of Solicited Adverse Events (AE).

2. Clinical Question

3. Trial Design

This completed Phase 3 trial evaluated safety and immunogenicity of PXVX0317 in healthy adults and adolescents. The registry lists randomized allocation, triple masking, and a parallel-group model. Its brief summary describes the study as double blind and placebo controlled; the registry’s masking field separately identifies triple masking. The record does not explain how the masking descriptions relate to one another.

The enrollment was 3258. Participants were assigned to one of three PXVX0317 lots or placebo: Group 1 received Lot 104, Group 2 received Lot 105, Group 3 received Lot 106, and Group 4 received placebo. The intervention names also identify CHIKV VLP/adjuvant and placebo. The primary outcome description specifies a safety population and combines all age strata.

The registry lists the study start as 2021-09-29 and primary completion as 2023-04-03, with status completed. The primary endpoint is incidence of solicited adverse events through Day 8, with a timeframe stated as 7 days post-vaccination. The record describes the assessed number as safety-population participants who completed a memory aid following vaccination. This definition matters because the counts used for the primary comparison need not match the distinct at-risk counts listed in the adverse-event summary.

The registry lists 19 outcome measures and 23 analyses. Eight secondary outcomes are posted, covering anti-CHIKV serum neutralizing antibody seroresponse rates, geometric mean titers, geometric mean fold increases, and the number and percentage meeting a titer and rise criterion at specified follow-up days. The numerical results for those secondary outcomes are not included in the record summarized for this analysis, so the statistical interpretation below is limited to the primary solicited-adverse-event results and the separate serious-adverse-event 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number of participants assessed is the number of safety population participants who completed a memory aid following the 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 Incidence of Solicited Adverse Events (AE), measured over 7 days post-vaccination.

The primary endpoint is the incidence of solicited adverse events (AEs), expressed as the number of participants with an event. It covers events recorded through Day 8, described as 7 days post-vaccination, and compares PXVX0317 groups with placebo for all age strata combined. The assessed population is defined as safety-population participants who completed a memory aid following vaccination.

A participant count is a binary outcome: for each person, the endpoint indicates whether an event was recorded or was not recorded within the specified period. Summarizing the number with an event and the number assessed gives a group-level event proportion. Comparing those proportions describes how frequently the endpoint occurred in the groups; it does not convey how many separate events an individual experienced, how long an event lasted, or its severity.

Solicited events are useful in a safety assessment because they are actively sought during a defined period after vaccination. A consistent observation window makes group comparisons interpretable in relation to that period. The endpoint is not a complete account of safety: it is limited to the solicited events, the stated follow-up interval, and participants included in the specified safety population. The registry record does not report the event list or additional details about collection procedures in the primary endpoint description.

7. Results Posted in the Registry

• Group 2: 39.7% (373/939) versus 35.2% (319/906) on control; risk difference 4.5 percentage points (95% CI 0.1 to 8.9), risk ratio 1.13 (1.00–1.27); unadjusted two-proportion z-test p = 0.045.
• Group 3: 39.8% (366/920) versus 35.2% (319/906) on control; risk difference 4.6 percentage points (95% CI 0.1 to 9.0), risk ratio 1.13 (1.00–1.27); unadjusted two-proportion z-test p = 0.044.
• Group 4: 27.1% (124/458) versus 35.2% (319/906) on control; risk difference -8.1 percentage points (95% CI -13.3 to -3.0), risk ratio 0.77 (0.65–0.92); unadjusted two-proportion z-test p = 0.002.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary outcome count?

The endpoint counts participants with at least one qualifying solicited adverse event in the stated follow-up window. General statistical explanation: an outcome recorded as event or no event is binary. For each group, the event count is interpreted relative to the number assessed in that group. This creates an observed group proportion, which is the basis for the posted risk differences. The proportions listed for the comparisons are 0.352 for Group 1, 0.397 for Group 2, 0.398 for Group 3, and 0.271 for placebo.

The denominators for the primary results are the numbers assessed under the endpoint definition: 906 for Group 1, 939 for Group 2, 920 for Group 3, and 458 for placebo. The endpoint description says participants were counted if they were in the safety population and completed a memory aid following vaccination. Separately reported adverse-event at-risk counts differ from these denominators. They belong to the separate adverse-event summary and should not be substituted for the primary comparison denominators.

What is a risk difference?

General statistical explanation: a risk difference subtracts one group’s event proportion from the other group’s event proportion. A value above zero means the first named group in the comparison has the higher observed proportion under the chosen subtraction order; a value below zero means it has the lower observed proportion. The posted comparisons use Group 1 as the reference. Group 2’s risk difference is 0.045, Group 3’s is 0.046, and placebo’s is -0.081. These quantities describe differences in observed proportions, not differences in the number of events per person.

The record also gives relative measures for each comparison: risk ratios and odds ratios, each with intervals. Those measures express comparisons on different scales from the risk difference. The principal interpretation uses the risk difference because it directly describes the absolute separation in the observed group proportions. The registry record does not identify a preferred measure or give a rationale for choosing one scale.

What does an unadjusted p-value say?

General statistical explanation: a p-value measures how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null model is true, and it does not quantify the size or practical importance of an effect. The posted unadjusted p-values are 0.045 for Group 2 versus Group 1, 0.044 for Group 3 versus Group 1, and 0.002 for placebo versus Group 1. “Unadjusted” means the reported values are not described as corrected for multiplicity. The statistical test and its detailed assumptions are not reported in the registry record.

How should the confidence intervals be read?

General statistical explanation: a confidence interval gives a range of estimates compatible with the observed data under a repeated-sampling procedure and the method’s assumptions. It conveys uncertainty around a point estimate; it is not a guarantee that the true value lies within the particular interval. The Group 2 interval is 0.001 to 0.089, the Group 3 interval is 0.001 to 0.090, and the placebo interval is -0.133 to -0.030. The record does not report the specific interval-construction method.

Why can extra variability matter?

General statistical explanation: over-dispersion occurs when observed variation is greater than a statistical model expects. For binary outcomes, a model that understates variability can make standard errors too small and intervals too narrow. The primary endpoint is a participant count, and no dispersion estimate is posted for it. The registry record does not report an over-dispersion assessment or a model-based adjustment, so no conclusion about whether such an adjustment was needed can be drawn from the record.

What is not specified about the analysis?

The registry record does not report the exact primary comparison test, a prespecified analysis model, covariate adjustment, stratification in the analysis, or a missing-data method. It also does not report the original trial sample-size justification, the planned power for the primary endpoint, or whether interim analyses were conducted. The outcome definition identifies the assessed population, but further details about exclusions and analysis-population handling are not reported in the registry record.

10. Confidence Intervals and Precision

The confidence intervals show the range of uncertainty around each posted risk-difference estimate. For Group 2 versus Group 1, the estimated risk difference is 0.045 and the interval runs from 0.001 to 0.089. For Group 3 versus Group 1, the estimate is 0.046 and the interval runs from 0.001 to 0.090. Both intervals have lower limits close to zero, while their upper limits allow a materially larger positive difference than the point estimates alone suggest.

For placebo versus Group 1, the estimated risk difference is -0.081, with an interval from -0.133 to -0.030. The interval remains on the negative side of zero. Interpreted on the posted comparison scale, the estimates indicate a lower observed endpoint proportion in placebo than in Group 1, while the interval reflects uncertainty about the size of that difference.

General statistical explanation: narrower confidence intervals indicate greater precision, while wider intervals indicate more uncertainty about the effect size. Precision depends on the amount of information and the variability in the data, as well as the method used. An interval does not establish clinical importance; the registry record does not report a threshold for a meaningful difference. Nor does a confidence interval resolve potential bias from missing observations, outcome ascertainment, or analysis choices.

The record gives the confidence limits rounded to the displayed values and does not report the interval method. The intervals should therefore be interpreted as the posted estimates, without assuming a particular adjustment or model. Because the p-values are unadjusted and multiplicity handling is not reported, the intervals also should not be interpreted as accounting for the number of comparisons.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning display gives illustrative participant counts per arm for comparisons based on the observed risk differences. These are not total event counts. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each planning scenario uses the stated fraction of the observed effect. The original trial’s own design assumptions and sample-size justification are not reported in the registry record.

For each comparison, the 80% power column indicates the number of participants per arm in a hypothetical study that would have an 80% chance of detecting the chosen effect under the stated assumptions. The 90% power column gives the corresponding per-arm count for a higher chance of detection under those assumptions. These are planning quantities, not descriptions of the enrollment or allocation that occurred in this trial. The sample-size illustrations are not observed power.

Rows that use 100% of the observed effect plan around the full observed risk difference. Rows using 75% or 50% plan around smaller effects. Smaller effects are harder to distinguish from random variation, so they require more participants under the same planning assumptions. For example, the Group 2 comparison lists 1,805 participants per arm for 80% power at 100% of the observed effect, 3,189 at 75%, and 7,130 at 50%. The corresponding 90% power figures are 2,415, 4,269, and 9,544 participants per arm.

The planning figures are recalculations from the posted summary statistics, not the trial’s original design plan. They should be read as conditional illustrations: changing the target effect or assumptions changes the required sample size. The curve and tabulated values are alternative ways to read these planning scenarios; neither represents the number of participants actually observed in a new study.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.352; treatment proportion p₁ = 0.397; average p̄ = 0.375.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6845 = 1.3417.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6838 = 0.5755.
4. n = (1.3417 + 0.5755)² / (0.0451)² = 1,804.3, rounded up to 1,805 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.352097130242826                          # control proportion
p1 <- 0.397231096911608                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(5072080)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 1,805 (80% power), 2,415 (90% power)
 75% of observed effect: n per arm = 3,189 (80% power), 4,269 (90% power)
 50% of observed effect: n per arm = 7,130 (80% power), 9,544 (90% power)
power.prop.test: 1804.3 
Simulated power at n = 1,805 per arm: 0.803 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The primary outcome is described for the safety population, defined for assessment as participants who completed a memory aid following vaccination. The registry record does not give further detail about how participants without a completed memory aid, or other missing outcome information, were handled. A missing-data method, imputation approach, or sensitivity analysis is not reported in the registry record.

The reported primary comparisons include Group 2 versus Group 1, Group 3 versus Group 1, and placebo versus Group 1. Their p-values are explicitly unadjusted. The registry record does not report a multiplicity procedure, a hierarchy among comparisons, or whether a particular comparison was designated as the principal inferential contrast. Because multiple comparisons can increase the chance of at least one apparently unusual result, the unadjusted p-values should not be treated as if a correction had been applied.

The record lists 19 outcome measures and 23 analyses, and it identifies eight posted secondary outcomes. The secondary outcome titles concern antibody seroresponse rates, geometric mean titers, geometric mean fold increases, and threshold-based antibody responses at specified days. Numerical secondary-outcome results and any multiplicity strategy for those outcomes are not reported in the registry record. These omissions prevent assessment of how the full set of outcomes and analyses was handled.

The record does not report the primary analysis model, whether comparisons were adjusted for baseline factors, or whether analyses were stratified by age. The primary outcome description states that all age strata are combined. It also does not report the details of a missingness assessment or the number excluded from the primary analysis for reasons other than memory-aid completion. These are limits on interpreting the reported estimates, not evidence that any particular procedure was or was not used outside what the registry record reports.

14. 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: appendicitis (0.2%), cholecystitis (0.1%), anaphylactic reaction (0.1%), craniocerebral injury (0.1%), femoral neck fracture (0.1%).

The separate serious-adverse-event summary lists the number at risk and the number affected for each group. Group 1 lists 10 affected among 918 at risk; Group 2 lists 7 among 945; Group 3 lists 6 among 927; and placebo lists 1 among 464. The same summary lists deaths as 0, 0, 1, and 0, respectively. These serious-event denominators differ from the denominators used for the primary solicited-adverse-event comparisons, so the two summaries should be read separately.

The record lists appendicitis at 0.2%, and cholecystitis, anaphylactic reaction, craniocerebral injury, femoral neck fracture, and gun shot wound at 0.1% each among the top serious-event terms. The listed terms and percentages do not establish whether an event was caused by vaccination. The registry record does not report a causal attribution for these counts or terms.

These are descriptive counts. The small number of serious events limits how precisely group differences can be estimated, and the record does not provide confidence intervals or comparative tests for this summary. The single listed death in Group 3 is a count in the registry record; it does not, by itself, establish a relationship to the intervention.

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

The primary results describe the proportion of assessed participants who had a solicited adverse event through Day 8 in each group. The observed proportions were 0.352 for Group 1, 0.397 for Group 2, 0.398 for Group 3, and 0.271 for placebo. The posted risk differences compare each of the other groups with Group 1: 0.045 for Group 2, 0.046 for Group 3, and -0.081 for placebo. The corresponding confidence intervals express uncertainty in these comparisons.

These findings do not establish why the group proportions differed, whether a difference is clinically important, or whether the same pattern would occur in another population or follow-up period. The registry record does not report a threshold for clinical importance, detailed missing-data methods, or multiplicity adjustment. The p-values are unadjusted, and the risk differences are calculated for the stated primary endpoint and analyzed populations.

The results are not a complete assessment of safety. The primary endpoint concerns solicited events over a defined period, while the separately posted serious-event summary contains relatively small event counts and no comparative confidence intervals. Neither summary alone characterizes every possible adverse event or longer-term outcome.

The trial’s stated objectives also include immunogenicity, and its secondary outcomes concern antibody measures at several days after vaccination. Numerical results for those outcomes are not reported in the registry record. Therefore, the primary adverse-event comparisons cannot answer the immunogenicity questions or support conclusions about antibody responses. The statistical interpretation is confined to what the posted primary and serious-adverse-event summaries measure.

16. Why This Trial Matters Statistically

This trial offers a useful setting for distinguishing several related but different statistical questions. Its primary endpoint is binary at the participant level: whether a solicited adverse event was recorded within a defined post-vaccination window. The group counts, denominators, proportions, risk differences, p-values, and confidence intervals each answer a different part of the interpretation. The counts show the observed data, the risk differences describe absolute contrasts, and the intervals show uncertainty around those contrasts.

The three-lot design also makes the comparison structure important. Group 2 and Group 3 are compared with Group 1, while placebo is also compared with Group 1. These are not interchangeable contrasts. The positive risk-difference estimates for the two other vaccine lots and the negative estimate for placebo each refer to a specific comparison and should be read alongside their own intervals and unadjusted p-values.

The study illustrates why statistical significance and precision are not the same as clinical importance. The confidence intervals quantify sampling uncertainty under an analysis method, but the registry does not supply a clinical-importance threshold or the full analysis plan. In addition, the p-values are unadjusted, and multiplicity handling is not reported. Careful interpretation therefore requires attention to the outcome definition, the assessed population, the comparison being made, and the limits of the posted analysis details.

Finally, the planning illustrations should not be confused with the trial’s actual design. They use observed effects to show how hypothetical per-arm sample sizes change when the target effect changes. This helps explain the relationship between effect size and planning needs without implying that those calculations were the rationale for the completed study.

17. 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 primary results are pooled across all age strata. Although the trial included healthy adults and adolescents, age-specific primary results are not reported in the registry record. The outcome description limits assessment to safety-population participants who completed a memory aid, but the registry does not provide further information about missing observations, exclusions, or sensitivity analyses.

The primary comparison estimates are accompanied by unadjusted p-values. A multiplicity adjustment, prespecified comparison hierarchy, and detailed analysis plan are not reported in the registry record. The specific statistical test, interval method, covariate adjustments, and any interim analyses are also not reported. These gaps limit assessment of the inferential framework and the role of the comparisons in the original trial plan.

The primary outcome is solicited adverse events through Day 8, not all adverse events over all follow-up. The separate serious-event summary lists counts and selected terms, but does not provide comparative confidence intervals or causal attribution. The numerical immunogenicity results are not reported in the record, even though antibody outcomes are listed as secondary measures.

Finally, the sample-size figures are planning illustrations based on the observed effects and stated assumptions, not the trial’s original sample-size justification. The original design assumptions are not reported in the registry record. These limitations do not invalidate the posted counts, but they constrain the conclusions that can be drawn from them.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Phase 3 Trial of the VLP-Based Chikungunya Vaccine PXVX0317 (CHIKV VLP Vaccine) — NCT05072080.
• Registry record last updated 2024-08-30; status last verified 2024-08.
• Results first posted 2024-08-30.
• 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.

21. Record Summary

The registry record describes a completed, randomized Phase 3, parallel-group trial of PXVX0317 in healthy adults and adolescents, with triple masking listed in the design fields. Enrollment was 3258, and four groups received three vaccine lots or placebo. The primary endpoint was the incidence of solicited adverse events through Day 8, assessed in safety-population participants who completed a memory aid.

The posted primary comparisons give risk differences of 0.045 for Group 2 versus Group 1, 0.046 for Group 3 versus Group 1, and -0.081 for placebo versus Group 1, with unadjusted p-values and confidence intervals. A separate serious-adverse-event summary reports counts by group. The registry lists antibody outcomes but numerical results for those outcomes are not reported in the registry record.