A Study on the Immune Response and Safety of Various Potencies of an Investigational Chickenpox Vaccine Compared With a Marketed Chickenpox Vaccine, Given to Healthy Children 12 to 15 Months of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on the Immune Response and Safety of Various Potencies of an Investigational Chickenpox Vaccine Compared With a Marketed Chickenpox Vaccine, Given to Healthy Children 12 to 15 Months of Age (NCT05084508), a randomized phase 2 study. The primary outcome is Concentrations of Anti-varicella Zoster Virus (VZV) Glycoprotein E (gE) Antibodies.

2. Clinical Question

3. Trial Design

This was a Phase II, randomized, controlled study with a parallel-group design. The registry describes the study as triple-masked and observer-blind. The planned enrollment was 800, and the record lists the study as completed. The recorded start date was 2022-02-03 and the primary completion date was 2024-02-09.

The study compared three investigational varicella vaccine potencies—low, medium, and high—with a pooled group receiving a licensed varicella vaccine from Lot 1 or Lot 2. All groups received the same listed co-administered vaccines on Day 1: measles, mumps, and rubella vaccine; hepatitis A vaccine; and 13-valent pneumococcal conjugate vaccine. The record does not describe how participants were allocated among the groups, or whether the two licensed vaccine lots were assigned in equal proportions.

The primary immunogenicity endpoint was assessed at Day 43 in the Per Protocol Set. The group-specific analysis counts were 171 for low potency, 159 for medium potency, 158 for high potency, and 161 for the pooled licensed-vaccine group. These counts describe the primary analysis population, not the planned enrollment. The registry record does not report a detailed participant-flow account explaining exclusions or the relationship between enrollment and the analysis populations.

The listed secondary outcomes include VZV gE seroresponse and solicited administration-site and systemic events, as well as unsolicited adverse events and serious adverse events. The record lists seven outcome measures, while the posted secondary results include seroresponse values and safety outcomes. The protocol’s allocation ratio, detailed masking procedures, follow-up schedule beyond the stated outcome timeframes, and reasons for completion 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.

Before assignment: * The Prevnar 13 vaccine was administered only to participants enrolled in the US and in countries where pneumococcal conjugate vaccine is recommended at 12- 15 months as per national immunization schedule. * As described in the protocol and analysis plan, participants in the varicella vaccine (VV) group are randomized into two lots (VV\_Lot1 and VV\_Lot2) and analyzed as pooled throughout the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Per Protocol Set (PPS), which included participants who received all study interventions as per protocol, were not unblinded, had immunogenicity results post-dose, complied with blood draw intervals, without intercurrent medical conditions that may interfere with immunogenicity and without prohibited concomitant medication/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 Concentrations of Anti-varicella Zoster Virus (VZV) Glycoprotein E (gE) Antibodies, measured over At Day 43.

The primary endpoint measures the concentration of antibodies against varicella zoster virus glycoprotein E, abbreviated VZV gE, at Day 43. These antibodies are one laboratory measure of the immune response after vaccination. The registry reports the outcome as a geometric mean concentration (GMC) for each group, with a 95% confidence interval. The unit is described as milli-international units per milliliter.

A geometric mean is used for measurements that are analyzed on a logarithmic scale and then expressed on the original scale. In general, this can be a useful summary when values are positive and their distribution is skewed, because a small number of very large measurements can pull an arithmetic mean upward. The geometric mean describes a group’s central antibody concentration; it does not describe every participant’s result or the spread of individual responses.

The registry reports GMCs of 960.0 for the low-potency group, 1071.0 for the medium-potency group, 1555.0 for the high-potency group, and 1284.0 for the pooled licensed-vaccine group. Their respective 95% confidence intervals are 843.0 to 1093.0, 952.0 to 1204.0, 1407.0 to 1718.0, and 1136.0 to 1453.0. These are group summaries at one stated timepoint. They do not, by themselves, establish a formal between-group difference, and the registry record does not report a primary statistical comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous laboratory measurement summarized as a geometric mean concentration. In general, geometric means are calculated by transforming positive measurements to a logarithmic scale, averaging on that scale, and transforming the result back. This approach can make a summary less sensitive to right-skew than an arithmetic mean. The posted results identify GMCs and confidence intervals, but the registry record does not report the precise transformation, handling of values below an assay threshold, or detailed estimation procedure.

A 95% confidence interval describes the uncertainty associated with an estimated group mean under the statistical model used. In general, it is a range produced by a method that, over repeated comparable studies and under its assumptions, would cover the corresponding true quantity at the stated rate. It is not a range containing 95% of individual participants’ antibody measurements, and it does not assign a 95% probability to the fixed true value. The posted intervals are specific to each group’s GMC. Because the record does not report a direct primary contrast, those intervals should not be used as though they were confidence intervals for differences between groups.

The primary analysis population is the Per Protocol Set. The record says this set included participants who received all study interventions as per protocol, were not unblinded, had post-dose immunogenicity results, and met blood-draw interval requirements. It also mentions excluding participants with intercurrent medical conditions that may interfere with the assessment, but the available wording is incomplete. In general, a per-protocol analysis can describe outcomes among participants meeting specified protocol requirements, but it may be affected by exclusions after randomization. The registry record does not report a complementary intention-to-treat primary analysis or the detailed rules used to determine analysis-set membership.

The secondary seroresponse outcome is binary: each participant either met the response criterion or did not, according to a definition. The registry reports percentages and 95% confidence intervals for each group. The definition and timing rules for seroresponse are not reported in the registry record. In general, a percentage is easier to interpret as a proportion of participants meeting a criterion, while a risk difference compares two such proportions by subtraction. The recalculated risk differences are unadjusted comparisons against the low-potency group. They are not identified as sponsor-reported analyses, and they do not account for multiple testing.

The medium-potency comparison has a risk difference of 0.027 and a 95% confidence interval from -0.021 to 0.074, with an unadjusted p-value of 0.275. The high-potency comparison has a risk difference of 0.052 and a 95% confidence interval from 0.011 to 0.092, with an unadjusted p-value of 0.016. A p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that null and the analysis assumptions were true. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. Because these comparisons are unadjusted secondary analyses, the p-values should not be read as confirmatory evidence.

The registry record lists no reported analyses for the outcome set. The recalculated contrasts are simple unadjusted calculations from the posted summary statistics, not a substitute for a sponsor’s prespecified analysis. The discrepancy flag is false, so there is no flagged disagreement between a posted sponsor estimate and a recalculation. However, the record does not give a sponsor-reported primary comparison for the antibody concentration endpoint.

The sample-size illustrations use the observed secondary seroresponse effects as planning inputs. The registry’s stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations consider detecting 100%, 75%, or 50% of the observed effect and give participants per arm for 80% and 90% power. In general, these are planning calculations: they show how required sample sizes can change when the effect targeted for detection is smaller. They are not observed power, do not describe the trial’s original design justification, and do not establish that the original study was adequately powered for a particular contrast. The actual sample-size justification and its assumptions are not reported in the registry record.

General statistical caution is warranted when outcomes are numerous or participants contribute repeated observations. Over-dispersion, when present, means that variability exceeds what a simple model assumes and can make standard errors too small if not handled appropriately. The available results do not establish that over-dispersion was present, and the registry record does not report a model that would permit judging how it was assessed. Details on missing-data handling, multiplicity adjustment, interim analyses, and the complete statistical analysis plan are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists several immunogenicity and safety outcomes, including the primary GMC endpoint and secondary seroresponse and adverse-event outcomes. It does not report how the family of outcomes was defined for hypothesis testing, whether any outcomes were designated as confirmatory beyond the primary endpoint, or whether an adjustment for multiple comparisons was planned. A multiplicity strategy is not reported in the registry record.

In general, repeated testing can increase the chance of at least one small p-value even when there is no real effect. Adjustments or a prespecified testing hierarchy can address that concern, but their purpose and consequences depend on the analysis plan. The unadjusted secondary seroresponse comparisons therefore have less evidential weight than a result from a prespecified, multiplicity-controlled analysis. The record does not report a primary GMC comparison that could be used to judge the trial’s central between-group hypothesis.

Missing-data methods are not reported in the registry record. The primary analysis is described as a Per Protocol Set and requires post-dose immunogenicity results and compliant blood-draw intervals. The record does not explain how missing antibody measurements were handled, how participants with incomplete follow-up were treated, or whether sensitivity analyses assessed the impact of missingness. It also does not report a full accounting of the participants excluded from the primary analysis.

The stated primary analysis population is not the same as every randomized participant: protocol adherence and available post-dose results are part of its description. In general, excluding participants after randomization can affect comparability if exclusion is related to treatment assignment or outcomes. The registry record does not report enough detail to assess that possibility or to compare the per-protocol findings with an analysis including all randomized participants.

Interim analyses, stopping rules, and the full statistical analysis plan are not reported in the registry record. The record also does not provide the sample-size justification used when the trial was planned. These omissions limit assessment of prespecification and the role of the posted results in the original testing strategy.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchiolitis (1.1%), respiratory syncytial virus bronchiolitis (1.0%), adenovirus infection (0.5%), croup infectious (0.5%), respiratory syncytial virus infection (0.5%).

The serious adverse event counts were 2 among 203 participants at risk in the low-potency group, 4 among 195 in the medium-potency group, 4 among 203 in the high-potency group, and 6 among 190 in the pooled licensed-vaccine group. The registry reports no deaths in any group. These are observed counts, not estimates of causal risk attributable to a vaccine.

Serious adverse events are different from solicited or other adverse events: seriousness generally reflects regulatory criteria such as outcomes or consequences, not necessarily the intensity of a symptom. The registry’s listed serious-event terms include bronchiolitis, respiratory syncytial virus bronchiolitis, adenovirus infection, infectious croup, respiratory syncytial virus infection, and dehydration. The record does not establish that these events were caused by study vaccination.

Interpretation is limited by the absence of a reported safety follow-up window, detailed event definitions, exposure-adjusted analyses, and information about event relatedness. The group counts should therefore be read descriptively. They do not establish that the groups have equal safety profiles, and they do not show that any listed event was caused by a particular intervention.

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

The posted results describe immune-response measurements and safety observations after vaccination in healthy children 12 to 15 months of age. For the primary endpoint, the reported Day 43 GMCs differ numerically across groups, with the largest estimate in the high-potency group. Those estimates are accompanied by group-specific confidence intervals, but the registry record does not report a formal primary between-group test. The observed ordering is therefore descriptive, not a conclusion of superiority or equivalence.

The secondary seroresponse results describe the proportion meeting a response criterion. Recalculated unadjusted comparisons show a positive estimated risk difference for each comparison against the low-potency group, with different degrees of uncertainty. They are secondary results and are not adjusted for multiple testing. The seroresponse definition and a clinical threshold for an important difference are not reported in the registry record, so statistical contrasts alone cannot establish clinical meaning.

The study also reports adverse-event counts, including serious events and no deaths. These figures describe what was recorded in the groups; they do not establish causation. A safety comparison requires information about observation periods, case definitions, event relatedness, and the statistical approach, which is not fully reported in the registry record.

These results do not establish how long the antibody response lasts, whether antibody levels predict protection against chickenpox, or how the vaccines compare on clinical disease outcomes. The posted primary endpoint is an antibody concentration at Day 43, not a measure of chickenpox cases. The registry record also does not report a clinical efficacy endpoint in the posted results.

Accordingly, the evidence supports a descriptive account of short-term immunogenicity and reported safety outcomes in the study populations. It does not by itself settle comparative clinical effectiveness, durability, clinical importance, or rare-event safety. Such conclusions would require additional outcome definitions, follow-up, and prespecified analyses beyond what is reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why the choice of summary measure matters in immunogenicity research. A geometric mean concentration summarizes the level of antibody response, whereas a seroresponse percentage summarizes how many participants cross a specified criterion. Those outcomes answer related but distinct questions. Reporting both can be informative, but interpretation depends on a clearly defined response threshold and an analysis plan that explains how the endpoints relate.

The registry reports group-specific primary estimates and confidence intervals, but no formal primary comparison. This distinction is important: estimates may have an apparent ordering while the record does not provide an inferential contrast designed to quantify the difference. A direct estimate of the between-group effect, with its uncertainty, is more useful for evaluating a comparative question than comparing separate confidence intervals by eye.

The secondary analyses illustrate another important principle. A nominal p-value from an unadjusted comparison does not account for the number of outcomes and comparisons examined. Statistical evidence should be interpreted in light of prespecification, multiplicity, effect size, and uncertainty. Here, the record does not report a multiplicity strategy, and the comparisons are recalculated from posted summary data rather than reported sponsor analyses.

The study also highlights the interpretive role of analysis populations. The primary endpoint uses a per-protocol population requiring protocol adherence and post-dose measurements. This can be relevant to immunogenicity summaries, but it makes transparent participant flow and sensitivity analyses important. The registry record does not provide enough detail to assess the influence of exclusions or missing measurements.

Finally, the planning illustrations based on observed secondary effects should not be confused with evidence of power in the completed study. They show how hypothetical future planning depends on the effect size selected, but the original design justification is not reported. Together, these points make the record useful for statistical appraisal while also showing where reporting detail is needed for stronger comparative conclusions.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation is that the registry record reports group GMC estimates and confidence intervals but no formal primary comparison. Consequently, the central comparative question cannot be evaluated from a reported contrast, standard error, or p-value. The confidence intervals describe group estimates and do not directly quantify differences between groups.

The primary analysis uses a Per Protocol Set, with requirements concerning interventions received, masking, post-dose measurements, and blood-draw intervals. The record does not give a complete participant-flow account, detailed exclusion counts, or a comparison with an analysis including all randomized participants. The full description of the population criteria is incomplete, and missing-data methods are not reported.

The secondary seroresponse outcome is difficult to interpret without its response definition. Its recalculated comparisons are unadjusted, and the record does not report a multiplicity plan or a prespecified hierarchy. The statistical analysis plan, sample-size justification, interim-analysis procedures, and missing-data sensitivity analyses are not reported in the registry record.

The primary measurement is at Day 43. The posted result does not establish durability of antibody response or clinical protection against chickenpox. The record does not report a clinical disease outcome alongside the primary immunogenicity measure. Safety interpretation is also limited by the absence of detailed follow-up windows, event definitions, relatedness assessments, and exposure-adjusted analyses.

Finally, the study population is described as healthy children 12 to 15 months of age. The posted results alone do not establish whether the findings apply to populations with different ages, health status, or vaccination histories. These are limits on interpretation of the registry results, not evidence that the results are invalid.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study on the Immune Response and Safety of Various Potencies of an Investigational Chickenpox Vaccine Compared With a Marketed Chickenpox Vaccine, Given to Healthy Children 12 to 15 Months of Age — NCT05084508.
• Registry record last updated 2025-02-28; status last verified 2025-02.
• Results first posted 2025-02-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT05084508 is a completed randomized, controlled Phase II study of investigational varicella vaccine potencies compared with a pooled licensed-vaccine group in healthy children 12 to 15 months of age. The design was parallel-group, and the record describes masking as triple and observer-blind. Planned enrollment was 800.

The primary outcome was anti-VZV gE antibody concentration at Day 43, reported as geometric mean concentrations with 95% confidence intervals in the Per Protocol Set. Secondary outcomes included seroresponse and adverse events. The registry reports no formal primary comparison, and the secondary contrasts discussed are unadjusted recalculations from posted summary results. Multiplicity procedures, missing-data methods, and the original sample-size justification are not reported in the registry record.