Long Term Immunity and Safety Following Vaccination With the JEV IC51 (IXIARO®, JESPECT®) in Pediatric Population In Non Endemic Countries. Uncontrolled, Ph3 FU-Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long Term Immunity and Safety Following Vaccination With the JEV IC51 (IXIARO®, JESPECT®) in Pediatric Population In Non Endemic Countries. Uncontrolled, Ph3 FU-Study (NCT01246479), a na phase 3 study. The primary outcome is Rate of Subjects With PRNT50 Titers of ≥ 1:10 at Month 12 After the First IC51 Vaccination (in Study IC51-322).

2. Clinical Question

3. Trial Design

This was an uncontrolled, Phase 3 follow-up study of long-term immunity and safety after pediatric participants received IC51 vaccination in parent study IC51-322. The registry record lists a single-group design, no masking, and allocation as not applicable. Enrollment was 23. The study is marked completed; its recorded start was 2010-10 and its primary completion was 2012-10.

The follow-up arm is named “No treatment,” and its description says participants would be followed for immunity through blood-sample analysis and for safety. This does not mean the participants had no vaccine exposure: IC51 had been given in the parent study. The intervention listing includes blood draw as a procedure and IC51 as a biological intervention given in IC51-322. The follow-up record therefore addresses later measurements and observations, rather than a new assigned vaccine treatment.

The primary outcome concerns the rate of participants whose PRNT50 titer reached the threshold of ≥ 1:10 at Month 12 after the first IC51 vaccination. The listed population is the intention-to-treat population, described in relation to seroprotection about one year after the primary vaccination series in IC51-322. Secondary outcomes cover geometric mean titers at Months 12, 24 and 36; the rate with titers of ≥ 1:10 at Months 24 and 36; and adverse-event and serious-adverse-event rates over follow-up periods extending to Months 12, 24 and 36.

Because there is only one follow-up group, the design can describe observations among participants in that group but cannot estimate a concurrent between-group treatment contrast. Details such as participant age range, eligibility criteria, exact visit windows, and the operational definition of the safety observation periods 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

Analysis population for the primary outcome, as defined in the registry: intention to treat population; assessment of seroprotection \~1 year post primary vaccination series in parent study IC51-322

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 Rate of Subjects With PRNT50 Titers of ≥ 1:10 at Month 12 After the First IC51 Vaccination (in Study IC51-322), measured over Month 12.

The primary endpoint is the rate of participants with PRNT50 titers of ≥ 1:10 at Month 12 after the first IC51 vaccination in parent study IC51-322. It is expressed as a percentage of participants. PRNT50 refers to a neutralization assay outcome: the endpoint classifies participants according to whether their measured neutralizing-antibody titer reaches the stated threshold. The record describes the assessment as seroprotection about one year after the primary vaccination series.

A threshold-based outcome makes a group-level summary understandable as the proportion meeting a prespecified antibody criterion. It does not show the full spread of individual titers, and it does not by itself establish how long any individual remains above the threshold beyond the assessment time. The registry record also lists geometric mean titers and threshold rates at later follow-up times as secondary outcomes, but numerical results for these outcomes are not reported in the registry record.

The endpoint’s listed precision measure is a 95% confidence interval. In general, a confidence interval conveys uncertainty around an estimated population quantity: narrower intervals indicate greater statistical precision, while wider intervals indicate greater uncertainty. The primary rate and its interval are not reported in the registry record, so the endpoint’s magnitude and precision cannot be assessed from the posted results.

As a single-group follow-up endpoint, the rate describes the participants assessed after vaccination in the parent study. Without a concurrent comparator, it cannot isolate the effect of vaccination from other influences or establish what the rate would have been without prior vaccination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s design and outcome definitions determine what statistical conclusions are available. It is a single-group, uncontrolled follow-up, with no masking and allocation not applicable. The primary endpoint is a percentage of participants crossing a stated PRNT50 threshold at a defined follow-up time. That endpoint can describe the observed group if the count and denominator are reported, but it does not provide a randomized treatment contrast. The registry record does not report the primary estimate, interval, or analysis details.

What does a threshold-rate endpoint measure?

A threshold-rate endpoint converts a laboratory measurement into a classification: each participant is counted as meeting or not meeting the specified criterion. The primary criterion is PRNT50 titers of ≥ 1:10 at Month 12 after the first IC51 vaccination. The resulting rate would describe the proportion meeting that criterion in the defined population and at the stated assessment time. It would not show the distribution of titers among participants, nor would it indicate how far above or below the threshold individual results fell.

The registry record lists geometric mean titers as secondary outcomes at Months 12, 24 and 36. A geometric mean is a summary of measurements on a multiplicative scale and can be useful for antibody titers, which are commonly interpreted through dilution steps. A group summary and a threshold rate answer different questions: the former summarizes the level of measurements, while the latter reports how many meet a criterion. No numerical geometric mean results are reported in the registry record.

How should the confidence interval be understood?

The primary outcome’s listed dispersion measure is a 95% confidence interval. In general, a confidence interval expresses sampling uncertainty around an estimate under the statistical method used. It is not a guarantee that the true value falls within the particular interval, and it does not measure all sources of uncertainty, such as limitations in outcome ascertainment or study design. The interval’s width helps readers judge statistical precision: a wider interval leaves more uncertainty about the underlying rate than a narrower one. Neither the primary interval nor the method used to calculate it is reported in the registry record.

For a percentage based on a limited group, the interval can be important because the observed rate may be imprecise. The enrollment was 23, but the number with an evaluable Month 12 result is not reported in the registry record. Enrollment should not automatically be treated as the denominator for an endpoint. A missing measurement or a population definition can change the denominator, and the record does not give the endpoint-specific count.

What does the single-group structure allow?

A single-group follow-up can describe measurements and events observed among those followed. It cannot, by itself, separate changes associated with prior vaccination from other influences over time. A comparator group would be needed for a direct contemporaneous contrast, and this registry record identifies none. The “No treatment” label should be read in context: IC51 had been administered in parent study IC51-322, while this follow-up monitored immunity and safety. It is not a randomized untreated arm.

The follow-up times are part of the estimand—the quantity the study intends to describe. The primary time point is Month 12 after the first vaccination in the parent study. Secondary immune outcomes extend to Months 24 and 36, while safety outcomes are listed through those same months. Estimates at different visits would concern different observation times and potentially different sets of participants. The record does not report whether the same participants contributed at each time or how changes in follow-up were handled.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variation is greater than a statistical model assumes. If a model expects outcomes to vary less than they actually do, standard errors may be too small and confidence intervals may be too narrow. Appropriate modeling can account for additional variability when the data and analysis call for it. The registry record does not report a model for the primary binary endpoint, any over-dispersion assessment, or a reason to apply a particular adjustment. These are general considerations, not a description of analyses documented for this study.

What can be inferred from safety counts?

Safety counts are descriptive unless a comparison and suitable analysis support a contrast. The record reports 2 participants with serious adverse events among 23 at risk and 8 with other adverse events among 23 at risk. These categories should not be added together: a participant may be represented in more than one event category, and the record does not clarify overlap. The serious-event terms listed are Staphylococcal infection and Tonsillitis, each at 4.3%. The record does not identify event-level timing, relatedness, or a comparative analysis.

The posted sample-size assumptions describe 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. Those assumptions are not evidence that the follow-up trial was designed or analyzed as a two-arm study. The record identifies this study as single-group and gives no trial-specific sample-size justification. Any planning illustrations are not observed power and do not replace the missing outcome estimate. Trial-specific choices about sample size, interim analyses, or statistical models 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("No Treatment")
n      <- c(19)
events <- c(17)
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  No Treatment  19  17  89.5  66.9  98.7  68.6  97.1  68.3  96.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists five outcome measures, including the primary threshold rate at Month 12 and secondary immune and safety outcomes at later follow-up times. When a study examines multiple outcomes or time points, the chance of at least one apparently notable result can increase if each is tested independently. In general, multiplicity procedures can control the interpretation of multiple statistical tests, or investigators can identify one primary outcome and treat the rest as supportive or descriptive. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or any adjustment for multiple testing.

The primary population is identified as the intention-to-treat population, but the record does not report how that population was defined in practice, how many participants were analyzed, or whether every enrolled participant had an evaluable result. The number enrolled was 23; the endpoint-specific denominator is not reported in the registry record. Thus, enrollment cannot be assumed to be the analysis denominator.

Missing-data handling is not reported in the registry record. The record does not describe whether missing measurements were excluded, imputed, or addressed through another approach, nor does it state how participants who missed follow-up assessments contributed to the different time-point outcomes. This matters because the people with observed measurements at later visits may not be identical to those assessed at the primary visit.

The registry record lists zero analyses, and the numerical primary outcome is not reported. It also does not report analysis populations for secondary outcomes, protocol deviations, or sensitivity analyses. These omissions prevent assessment of how the planned endpoint was translated into an analysis and how robust any estimate might be to missing data or analytic choices.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: staphylococcal infection (4.3%), tonsillitis (4.3%).

The safety figures are descriptive observations from the single follow-up group. The record reports 2 participants with serious adverse events among 23 at risk, and 8 participants with other adverse events among 23 at risk. It lists Staphylococcal infection and Tonsillitis as serious-event terms, each reported as 4.3%. The registry record does not report deaths.

These counts should not be interpreted as comparative risks because there was no concurrent control group. The follow-up group had received IC51 in parent study IC51-322, and the listed “No treatment” arm refers to observation without a new treatment assignment in the follow-up. The figures alone cannot establish whether an event was caused by vaccination, nor do they show how rates compare with another group.

Serious adverse events and other adverse events are distinct reporting categories; the record does not specify whether the participants overlap across categories. The term-level percentages should not be treated as a complete description of event severity, timing, recurrence, or relatedness. Those details are not reported in the registry record. The figures therefore describe recorded events in this group, not a stand-alone comparative safety assessment.

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

This study was designed to follow immunity and safety in pediatric participants who had received IC51 in parent study IC51-322. Its primary endpoint asks what proportion had PRNT50 titers of ≥ 1:10 at Month 12 after the first vaccination. The registry record gives the endpoint definition and the intended analysis population, but does not report the resulting rate or its 95% confidence interval. It is therefore not possible to judge the numerical level of the primary outcome or its statistical precision from the registry record.

The listed secondary outcomes would add information about antibody levels and threshold rates at Months 12, 24 and 36, along with adverse-event observations over follow-up. Their numerical results are not reported in the registry record. Without those results, the record cannot show the observed course of antibody measurements across visits or the frequency of each listed safety outcome over time.

The safety information that is reported consists of 2 participants with serious adverse events among 23 at risk, 8 participants with other adverse events among 23 at risk, and two named serious-event terms, each at 4.3%. These counts describe the follow-up group. Because the study has no concurrent comparator, they do not provide a comparative estimate or establish that an event was caused by vaccination. The registry record does not report deaths.

More broadly, an antibody threshold is a laboratory outcome, not a direct measure of clinical protection against disease in this study. The registry record does not report a clinical disease endpoint or a comparison capable of establishing clinical benefit. The study’s design can support descriptive follow-up if outcome results are available, but the missing numerical estimates and analysis details limit what can be concluded from this record. Neither a positive nor a negative conclusion about the primary endpoint can be drawn from an outcome result that is not reported.

14. Why This Trial Matters Statistically

Long-term follow-up asks a different question from measurement immediately after vaccination: whether laboratory markers and safety observations are recorded at later intervals. This registry record specifies antibody outcomes at Months 12, 24 and 36 after the first vaccination in IC51-322, and safety outcomes over periods extending to those months. Such time-specific definitions help clarify what a follow-up study intends to describe.

Statistically, the key feature is the single-group design. It can document outcomes among participants who were followed, but it does not provide a contemporaneous control for separating the contribution of prior vaccination from other factors. That distinction matters when interpreting any apparent persistence in an antibody measure or the occurrence of an adverse event.

The record also illustrates why outcome definitions and result reporting must be considered together. The primary outcome is stated as a threshold rate, with a 95% confidence interval designated as its precision measure. Yet the estimate, interval, and endpoint-specific denominator are not reported. A precisely worded endpoint is not enough to assess the result without its data and uncertainty.

The safety counts make a separate statistical point: event totals should be interpreted in their stated denominator and design context. In an uncontrolled follow-up with 23 enrolled participants, counts can describe what was recorded but do not supply a comparative risk estimate. The listed serious-event terms and percentages should not be treated as causal evidence.

Finally, the registry record leaves important analytic details unreported, including missing-data handling and multiplicity strategy. These details influence how outcome estimates should be understood when several outcomes and time points are considered. The study is therefore statistically informative as a defined follow-up design, while the missing results and methods prevent a fuller assessment of its intended questions.

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 most immediate limitation is that the numerical primary endpoint result is not reported in the registry record. Neither the Month 12 rate of participants with PRNT50 titers of ≥ 1:10 nor its 95% confidence interval is available. The listed secondary immune and safety outcomes likewise do not have numerical results in the record, despite the outcome definitions and follow-up times being specified.

The study is uncontrolled and single-group. Participants had received IC51 in parent study IC51-322, but there is no concurrent comparator in this follow-up. Consequently, the design cannot provide a randomized contrast, and recorded antibody or safety observations cannot be compared with an untreated group from this record. The “No treatment” arm label should not be mistaken for a no-vaccine history.

Enrollment was 23, but the record does not report the endpoint-specific numbers assessed or the number included in each analysis. This prevents confirmation that the enrolled count equals the denominator for any outcome. Missing-data procedures, follow-up completeness, and handling of incomplete observations are not reported in the registry record.

Other details needed to assess generalizability and analysis are also absent, including participant age range and baseline characteristics, the statistical model, sample-size justification, multiplicity handling, and sensitivity analyses. The registry record lists five outcome measures and zero analyses. It does not report deaths. The available safety counts and serious-event terms are descriptive, and information on timing, relatedness, recurrence, and overlap between event categories is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Long Term Immunity and Safety Following Vaccination With the JEV IC51 (IXIARO®, JESPECT®) in Pediatric Population In Non Endemic Countries. Uncontrolled, Ph3 FU-Study — NCT01246479.
• Registry record last updated 2020-03-18; status last verified 2020-03.
• Results first posted 2015-04-29.
• 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

This completed, uncontrolled Phase 3 follow-up study enrolled 23 pediatric participants in non-endemic countries who had received IC51 in parent study IC51-322. The recorded study period began in 2010-10, with primary completion in 2012-10. The follow-up used blood draws to assess immunity and monitored safety; it had a single group, no masking, and allocation listed as not applicable.

The primary outcome was the rate with PRNT50 titers of ≥ 1:10 at Month 12. Secondary outcomes included antibody measures at Months 12, 24 and 36 and safety outcomes over follow-up. The primary rate, its 95% confidence interval, and numerical secondary results are not reported in the registry record. Safety counts include 2 participants with serious adverse events and 8 with other adverse events among 23 at risk; deaths are not reported in the registry record.