A Phase 2 Clinical Trial of VLA1553 in Healthy Children Aged 1 to 11 Years: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2 Clinical Trial of VLA1553 in Healthy Children Aged 1 to 11 Years (NCT06106581), a randomized phase 2 study. The primary outcome is Number of Participants With Solicited Injection Site Reactions.

2. Clinical Question

The study was randomized, observer-blinded, and conducted in parallel groups. It was a Phase 2 trial with three arms. Results are reported by age bands of 1-2, 3-6, and 7-11 years, making age-specific context important when interpreting the counts. The registry record lists 31 outcome measures, with 27 secondary outcomes posted. It describes a broad safety assessment as well as the primary injection-site reaction endpoint.

3. Trial Design

The registry record identifies this as a randomized, observer-blinded, parallel-group Phase 2 trial of two dose formulations of VLA1553 and a control in healthy children aged 1 to 11 years. It is described as multicenter and prospective. The masking field is recorded as quadruple. Enrollment was 304, and the trial status is completed.

The brief summary describes an intended allocation of 2:2:1: 120 children in the full-dose group, 120 in the half-dose group, and 60 in the control group. Those are planned group sizes in the summary, not the subgroup denominators for the primary outcome. The posted primary outcome data are broken out by age band and treatment group. The denominators vary across those groups; for example, the 7-11-year groups have 40, 43, and 21 participants, respectively. The record does not explain why these outcome denominators differ from the planned enrollment distribution.

The comparison results use the control group aged 7-11 years as the reference, with 7 participants affected among 21 at risk. This is important for reading the age-stratified entries: the comparisons for children aged 1-2 and 3-6 years are not presented against their own age-matched control groups. The record also reports counts for those younger control groups, but does not provide a separate adjusted analysis by age.

The registry record does not report the trial's original sample-size justification, detailed randomization procedure, or statistical analysis plan. The planning illustrations associated with the observed results are separate from the trial's original design assumptions. The record lists no posted analyses, while providing outcome-level counts and comparisons.

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: Safety 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 Number of Participants With Solicited Injection Site Reactions, measured over within 14 days post-vaccination.

The primary endpoint is the number of participants with solicited injection-site reactions within 14 days after vaccination. Its description includes the frequency and severity of solicited injection-site and solicited systemic reactions during that period. The posted primary outcome title, however, is specifically about participants with injection-site reactions. The results presented by group are counts of participants affected, rather than counts of individual reaction episodes.

A participant-based count is useful for describing how many people in each group experienced at least one event in the defined period. It gives a direct summary of the occurrence of reactions without treating multiple events in one participant as multiple affected participants. The endpoint's specified observation window also makes the period of interest explicit.

The primary outcome is a safety and tolerability measure, not a direct measure of immune response or protection from infection. The trial title and summary identify immunogenicity as an area of evaluation, but the posted primary endpoint described in these results concerns reactions. The record does not provide a separate numerical immunogenicity result in the registry record for this analysis.

Counts are reported separately for the three age bands and three study groups. They should be interpreted alongside their denominators: the same count can convey different information in groups of different sizes. The endpoint description mentions severity, but the group results presented for this primary measure do not give a severity breakdown. The registry record does not report the operational criteria used to classify an event as solicited or to grade its severity.

7. Results Posted in the Registry

• VLA1553 Half Dose - 7-11 Years: 30.0% (12/40) versus 33.3% (7/21) on control; risk difference -3.3 percentage points (95% CI -28.0 to 21.3), risk ratio 0.90 (0.42–1.94); unadjusted two-proportion z-test p = 0.789.
• VLA1553 Full Dose - 7-11 Years: 18.6% (8/43) versus 33.3% (7/21) on control; risk difference -14.7 percentage points (95% CI -38.0 to 8.5), risk ratio 0.56 (0.23–1.33); unadjusted two-proportion z-test p = 0.192.
• VLA1553 Half Dose - 3-6 Years: 15.0% (6/40) versus 33.3% (7/21) on control; risk difference -18.3 percentage points (95% CI -41.3 to 4.7), risk ratio 0.45 (0.17–1.17); unadjusted two-proportion z-test p = 0.097.
• VLA1553 Full Dose - 3-6 Years: 17.5% (7/40) versus 33.3% (7/21) on control; risk difference -15.8 percentage points (95% CI -39.2 to 7.5), risk ratio 0.53 (0.21–1.30); unadjusted two-proportion z-test p = 0.162.

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is binary at the participant level: each person is counted as having or not having a solicited injection-site reaction in the defined period. The group summaries therefore give the number affected and the number at risk. This type of outcome differs from a continuous measure, such as a laboratory value, where the analysis would usually focus on means or other summaries of a numerical scale.

A risk difference expresses the difference between the proportions affected in two groups. A negative estimate in the posted comparisons means the proportion in the named group is lower than in the reference group, according to the calculation used for those results. A value near zero would indicate little observed difference in proportions. The confidence interval describes a range of values reasonably compatible with the data under the method used. If it includes zero, the data are compatible with no risk difference as well as with differences in either direction.

The posted results also include unadjusted p-values. A p-value measures how incompatible the observed data are with a specified null hypothesis under the statistical model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. An unadjusted p-value does not account for the fact that several comparisons are being considered. The registry record does not report the inferential method used to calculate these particular confidence intervals and p-values, nor a prespecified threshold or analysis plan for interpreting them.

For all posted risk-difference comparisons, the reference group is the control group aged 7-11 years. This is visible in the same reference count and denominator across the comparisons: 7 affected participants among 21. As a result, the estimates for the younger age bands compare each listed group with that older control group. A comparison between a dose group and its age-matched control would use a different reference group; that is not the contrast represented by these posted estimates. The separate counts for control participants aged 3-6 and 1-2 years are available, but their comparisons with the 7-11-year control group should not be mistaken for treatment contrasts.

Randomization is intended to make treatment groups comparable with respect to measured and unmeasured characteristics, on average, when the allocation and analysis are carried out as planned. It does not ensure that every subgroup is balanced, especially when groups are small. Observer blinding can reduce the influence of knowledge of assignment on observation or assessment, but the registry record does not describe the exact masking procedures or the roles included in the quadruple-masking designation. The record identifies a parallel design, meaning participants were assigned to one study group rather than crossing between interventions.

Age-band results are useful for showing the observed distribution across the trial's stated age categories, but subgroup estimates are typically less precise than an overall comparison because each contains fewer participants. Moreover, comparing each subgroup to one fixed reference age group means age and treatment are not separated in the same way as in a within-age comparison. The posted results do not give a model adjusting for age or a test of whether treatment effects differ by age. Such analyses and their assumptions are not reported in the registry record.

The primary endpoint description refers to both frequency and severity, while the numerical primary results are counts of participants with an event. A count of affected participants does not reveal whether an individual's reaction was mild or severe, nor how many reactions occurred per affected participant. Severity is listed among secondary outcomes for adverse events, but the detailed severity breakdown for the primary injection-site reactions is not part of the registry entries summarized in these results. The operational definitions of solicited reactions, their severity grading, and any handling of missing observations are not reported in the registry record.

The broader safety summary distinguishes serious adverse events from other adverse events and reports participants at risk and affected. These categories should not be conflated with the primary solicited reaction endpoint. An adverse event is not automatically caused by the intervention; establishing a causal relationship requires clinical and analytic assessment beyond a count alone. The registry record's reported group counts can describe what occurred during the reported safety assessment, but the exposure windows and event-attribution rules are not included in the registry record for this interpretation.

The record lists 31 outcome measures and 27 posted secondary outcomes. Considering many outcomes or comparisons raises multiplicity concerns: even when each test is conducted at a nominal significance level, the chance of at least one small p-value across a collection of tests can increase. Methods such as prespecifying a primary contrast, adjusting for multiple comparisons, or treating secondary findings as exploratory can address this issue, but the registry record does not state which approach was used. The absence of a reported analysis plan also means the prespecification of subgroup contrasts and analytic choices cannot be verified from this record.

10. Confidence Intervals and Precision

Precision concerns how narrowly the data locate an estimated effect. A confidence interval conveys this uncertainty: a narrow interval indicates a more precise estimate, while a wide interval leaves a broader range of plausible effects. For the risk differences in this trial, intervals that span zero include the possibility of no difference as well as effects in either direction. That applies to both dose-group comparisons in the 7-11-year band and both dose-group comparisons in the 3-6-year band.

The posted intervals for the 1-2-year dose-group comparisons exclude zero, as do the comparisons of the younger control groups with the 7-11-year control reference. This describes the interval locations, not the clinical importance of the differences. The intervals are based on small subgroup denominators, and the registry record does not specify the confidence-interval method. In particular, the presentation does not provide an adjusted interval that accounts for multiple comparisons or age structure.

Group size affects precision for a binary outcome: when fewer participants contribute information, an estimate can be sensitive to a small number of events. The outcome denominators range across the age and treatment groups, so precision is not identical for every comparison. A point estimate alone can therefore give an incomplete impression of the evidence. The interval and the specific reference group are both necessary to interpret a comparison.

Precision is distinct from bias and from clinical importance. A narrow interval would not correct a systematic problem in how participants or events were measured, while a statistically precise difference would not by itself establish that the difference matters clinically. The registry record does not report a prespecified clinically meaningful threshold for injection-site reactions or an adjusted analysis of these 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 sample-size illustrations are planning calculations based on the observed effect, not the trial's original design assumptions. The registry record does not report the original sample-size justification. For these binary outcome comparisons, the figures are participants per arm, rather than a total number of events. The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario targets the stated fraction of the observed effect.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect, under those assumptions, if that effect were the true one. The 90% power column gives the corresponding per-arm number for a higher chance of detecting it. These are hypothetical planning quantities, not descriptions of the trial's actual group sizes or results.

Each row's effect fraction changes the size of the difference the calculation is designed to detect. Planning for 75% or 50% of the observed effect means targeting a smaller effect than planning for the full observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants. This relationship is also what the sample-size curve is meant to illustrate: required enrollment rises as the effect to be detected becomes smaller, given the stated calculation assumptions.

The estimates are especially sensitive to the observed effect because the calculations use it as their starting point. In a small subgroup, an observed effect may be imprecise, and a planning result based on it can be unstable. These scenarios should therefore be read as illustrations for future planning, not as evidence about the adequacy of the original trial or the probability that its findings are correct. They are not observed power.

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 = 0.333; treatment proportion p₁ = 0.300; average p̄ = 0.317.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6579 = 1.2894.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6574 = 0.5533.
4. n = (1.2894 + 0.5533)² / (-0.0333)² = 3,056.0, rounded up to 3,056 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 <- 0.333333333333333                          # control proportion
p1 <- 0.3                          # 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(6106581)
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 = 3,056 (80% power), 4,091 (90% power)
 75% of observed effect: n per arm = 5,472 (80% power), 7,325 (90% power)
 50% of observed effect: n per arm = 12,397 (80% power), 16,595 (90% power)
power.prop.test: 3056 
Simulated power at n = 3,056 per arm: 0.808 (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 registry record lists 31 outcome measures and 27 posted secondary outcomes, alongside several age-specific comparisons for the primary endpoint. Considering multiple outcomes and contrasts creates a multiplicity issue: the more tests considered, the greater the opportunity for a small p-value to arise by chance, even if no underlying difference exists. The posted p-values are identified as unadjusted. The registry record does not report a multiplicity-control procedure or a hierarchy specifying which comparisons were primary, secondary, or exploratory.

The record does not provide a detailed statistical analysis plan. It therefore does not report whether the age bands or contrasts were prespecified, what model was intended, how confidence intervals were constructed, or what approach was planned for missing endpoint data. These matters affect how strongly the p-values and intervals can support a confirmatory interpretation. The number of outcome measures alone does not establish that every outcome was tested in the same way, and no such assumption is made.

The primary endpoint identifies the Safety Population, but the record excerpt does not define its membership or explain whether all randomized participants were included in each outcome denominator. The posted subgroup denominators are not the same as the enrollment target by arm, and the record does not describe the reasons for exclusions, missing assessments, or any imputation. No conclusion about missingness can be drawn from the event counts alone.

The comparison reference is also relevant to multiplicity and interpretation. The posted dose-group comparisons use the 7-11-year control group, rather than age-matched controls for every band. The record does not report a model that adjusts for age, an interaction analysis, or an age-specific treatment contrast plan. The results should accordingly be read as the comparisons actually posted, without treating them as a complete adjusted analysis of treatment effects across ages.

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: pneumonia (5.0%), cellulitis (2.5%), appendicitis perforated (2.5%), asthmatic crisis (2.4%), drug hypersensitivity (2.4%).

The safety summary reports participants at risk and participants with serious adverse events for each age and treatment group. The serious-event counts were 1 in the half-dose group and 2 in the full-dose group among children aged 7-11 years; 1 and 0, respectively, among children aged 3-6 years; and 0 and 2, respectively, among children aged 1-2 years. The control counts were 0, 0, and 1 in the corresponding age bands. The record reports zero deaths in every listed group.

These are participant counts, not event totals, and the denominators differ across groups. They describe the serious adverse events recorded in the registry results, but do not establish whether an event was caused by a study intervention. The record also lists serious-event terms with percentages, including pneumonia and other terms, but the registry entries do not provide enough context to interpret those percentages as comparative risks across arms. The safety figures should be considered alongside the separate non-serious adverse-event results and the trial's defined observation periods, which are not fully specified in the registry record.

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

The posted data show how many participants in each age and treatment group experienced solicited injection-site reactions within the endpoint's 14-day period. They also show risk-difference comparisons using the 7-11-year control group as the reference. Several of the dose-group intervals include no difference, while the intervals for the two dose groups aged 1-2 years exclude zero. This describes the numerical pattern and its statistical uncertainty; it is not a determination of clinical benefit or harm.

Interpretation is limited by the contrast structure. The younger age-group dose results are not compared with the control groups in their own age bands in the posted risk-difference results. The separate control counts show variation across age groups, reinforcing the need not to interpret an age-related contrast as a vaccine-versus-control contrast. The record does not report an age-adjusted analysis or a treatment-by-age analysis.

The unadjusted p-values do not account for the set of comparisons across age bands and outcomes. The registry record lists multiple outcome measures but does not report a multiplicity procedure, detailed analysis plan, or missing-data approach. Confidence intervals communicate uncertainty for individual comparisons, but they do not by themselves resolve these design and analysis limitations.

These endpoint findings do not establish whether VLA1553 prevents chikungunya infection, nor do they describe immune response results. The trial title refers to immunogenicity, but the endpoint examined is a solicited reaction measure. Likewise, adverse-event counts alone do not establish causal relationships or provide a complete assessment of safety. The results are best understood as reported clinical-trial observations with limited precision in the age-stratified groups.

16. Why This Trial Matters Statistically

This trial is statistically informative because it makes clear how the structure of a comparison can shape interpretation. Although results are separated into age bands, the posted risk differences use the same control reference group aged 7-11 years. That means a contrast labelled by a younger age group is not automatically an age-matched treatment comparison. Keeping the reference group explicit prevents age differences from being mistaken for dose effects.

The outcome is a count of participants with an event, so denominators matter as much as the affected counts. The age-stratified groups are modest in size, and a small number of participants can influence the estimated proportion. Confidence intervals help show that uncertainty, while the unadjusted p-values indicate only how the individual observed contrasts relate to a null hypothesis under the analysis used.

The registry record includes multiple outcomes and comparisons, yet does not report a multiplicity strategy or a detailed analysis plan. This is a useful reminder that individual p-values need context when many results are considered. It also matters that planning calculations derived from observed effects can be highly sensitive to those effects; such illustrations do not replace prospective design assumptions.

Finally, safety endpoints, immunogenicity, and clinical protection answer different questions. Injection-site reaction counts contribute to the description of tolerability, but they do not determine immune response or disease prevention. Separating those questions is essential to a disciplined reading of a Phase 2 trial.

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 available primary endpoint results are stratified by age, but the posted risk-difference comparisons use the control group aged 7-11 years as a common reference. They therefore do not provide the age-matched dose-versus-control contrasts for the 1-2 and 3-6-year groups. The record does not report an adjusted model to account for age or an analysis of whether treatment effects differ by age.

The group denominators are relatively small and differ across age and intervention groups. This constrains precision, particularly when event counts are low. The record does not explain how the primary outcome denominators relate to enrollment, whether any participants were excluded from the Safety Population, or how missing assessments were handled.

The endpoint description includes frequency and severity, but the primary results summarized are participant counts without a severity breakdown. Operational definitions for solicited reactions and severity grading are not reported in the registry record. The record also does not provide detailed outcome observation windows for the broader adverse-event measures.

Several outcomes and comparisons are reported, but the registry record does not state a multiplicity adjustment, a complete statistical analysis plan, or the original sample-size assumptions. The posted planning illustrations are based on observed effects and should not be treated as confirmation of the initial design. These limitations restrict the strength and scope of conclusions that can be drawn from the reported comparisons.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Phase 2 Clinical Trial of VLA1553 in Healthy Children Aged 1 to 11 Years — NCT06106581.
• Registry record last updated 2026-08-13; status last verified 2025-08.
• Results first posted 2026-08-13.
• 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

NCT06106581 is a completed, randomized, observer-blinded, parallel-group Phase 2 trial of full-dose VLA1553, half-dose VLA1553, and a control in healthy children aged 1 to 11 years. The registry record reports enrollment of 304 and describes a planned distribution of 120 participants in each vaccine group and 60 in control.

The primary outcome counts participants with solicited injection-site reactions within 14 days after vaccination. Results are reported across age bands, and the posted risk-difference comparisons use the 7-11-year control group as the reference. Estimates vary across groups and have differing precision; several intervals include no difference. The record also reports serious adverse-event counts and zero deaths in each group. Detailed analysis-plan, missing-data, and multiplicity methods are not reported in the registry record.