Evaluation of the Immunogenicity and Safety of VARIVAX™ in Healthy Russians (V210-058): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Immunogenicity and Safety of VARIVAX™ in Healthy Russians (V210-058) (NCT03843632), a na phase 3 study. The primary outcome is Varicella Zoster Virus (VZV) Antibody Response Rate at 6 Weeks Post Last Vaccination in Participants Who Were Seronegative at Baseline.

2. Clinical Question

The study asked whether participants who were seronegative at baseline had a VZV antibody response after vaccination with VARIVAX™. The primary endpoint defined response as a post-vaccination antibody titer of at least 5 gpELISA units/mL among participants whose baseline titer was <1.25 gpELISA units/mL. The registry describes this endpoint for children after Vaccination 1 and for adults and adolescents after Vaccination 2.

The study enrolled healthy Russian children, adolescents, and adults aged 12 months and older. Participants were grouped by age: 12 months to 6 years, 7 to 12 years, 13 to 17 years, and 18 to 75 years. The planned intervention was VARIVAX™, given subcutaneously. Children were assigned one dose in the study schedule described in the record; adults and adolescents aged 13 years and older were assigned a second dose as well.

This was a single-arm study, not a comparison of VARIVAX™ with a placebo or another vaccine. It therefore addresses the observed antibody response and safety experience in the enrolled groups, rather than a between-treatment difference. The brief summary states that no formal hypothesis was tested. The registry record does not report the primary response rate, its confidence interval, or age-specific response estimates, so the magnitude and precision of the antibody response cannot be assessed from the record’s reported results.

3. Trial Design

This was a Phase 3, open-label, multicenter, single-arm study of VARIVAX™ in healthy Russian individuals aged 12 months and older. The registry lists an enrollment of 150 and describes four age groups: adults aged 18 to 75 years, adolescents aged 13 to 17 years, children aged 7 to 12 years, and children aged 12 months to 6 years. The study was completed. The record gives a start date of 2019-03-01 and a primary completion date of 2020-06-19.

All participants were to receive one subcutaneous dose on Day 1. Adults and adolescents aged 13 years and older were also to receive a second subcutaneous dose on Day 43. The primary antibody-response assessment was scheduled 6 weeks after the last vaccination: after Vaccination 1 for children and after Vaccination 2 for adults and adolescents. The stated timeframes were up to approximately 43 days for children and up to approximately 86 days for adults and adolescents.

Open-label means participants and study personnel were not masked to the assigned intervention. A single-arm design has no concurrent randomized control group, so outcomes cannot be interpreted as a direct comparison with another intervention or with no vaccination. The registry lists allocation as not applicable and masking as none. The brief summary says that no formal hypothesis was tested. Further details about recruitment, conduct across centers, protocol deviations, and the statistical analysis plan are not reported in the registry record.

The registry’s safety groups include 50 adults, 30 adolescents, 33 children aged 7 to 12 years, and 37 children aged 12 months to 6 years at risk for the reported events. These are the denominators stated for the safety summaries; they should not be assumed to be the analysis denominators for the primary immunogenicity endpoint.

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: 150 participants were enrolled and received VARIVAX™ on study. Adults and Adolescents received 2 vaccinations on study and children received 1 vaccination.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All allocated participants without deviations from the protocol that would substantially affect the results of the immunogenicity outcome measures (Per-Protocol population) who were seronegative at baseline and who received Vaccination 1 (children) or Vaccination 1 and Vaccination 2 (adults and adolescents) were analyzed.

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 Varicella Zoster Virus (VZV) Antibody Response Rate at 6 Weeks Post Last Vaccination in Participants Who Were Seronegative at Baseline, measured over Adults and Adolescents: 6 weeks post Vaccination 2 (up to approximately 86 days), Children: 6 weeks post Vaccination 1 (up to approximately 43 days).

The primary endpoint was the VZV antibody response rate among participants who were seronegative at baseline. Blood antibody titers were measured with a glycoprotein enzyme-linked immunosorbent assay, or gpELISA. A participant counted as a responder if the post-vaccination titer was at least 5 gpELISA units/mL and the baseline titer was <1.25 gpELISA units/mL. The outcome is a percentage of participants, with a 95% confidence interval specified as the measure of uncertainty.

The endpoint was assessed 6 weeks after the last scheduled vaccination. For children, that meant 6 weeks after Vaccination 1; for adults and adolescents, it meant 6 weeks after Vaccination 2. The stated timeframes were up to approximately 43 days and up to approximately 86 days, respectively. These different schedules matter when interpreting age-group results: the endpoint follows the last dose specified for each group rather than a common dose number for every participant.

An antibody-response endpoint provides a laboratory measure of immune response under the study’s defined assay and threshold. It is not itself a comparison of clinical outcomes between treatments. The registry record does not report the response rate or its 95% confidence interval. It also does not provide the age-specific primary endpoint results in the registry entries, so neither the observed response level nor its precision can be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response summarized as a percentage: each eligible participant either meets the antibody threshold or does not. The registry defines a responder as having a post-vaccination VZV antibody titer of at least 5 gpELISA units/mL, provided the baseline titer was <1.25 gpELISA units/mL. The assay is identified as gpELISA. The outcome therefore depends on both the laboratory measurement and the threshold chosen in the endpoint definition.

What does the response percentage represent?

In general, a response percentage describes the proportion of participants in a defined analysis population who meet the response rule. Its interpretation depends on the population used in the denominator, the handling of missing measurements, and the timing of assessment. The registry describes the primary population as per-protocol participants who were seronegative at baseline and received the vaccination schedule relevant to their age group. The full population wording is incomplete in the record, and further details about how participants were selected for this analysis are not reported in the registry record.

The primary endpoint has different last-dose timing by age group. Children were assessed 6 weeks after Vaccination 1, while adults and adolescents were assessed 6 weeks after Vaccination 2. A response percentage for one group would therefore describe that group at its specified assessment point; it should not automatically be treated as a result at an identical dose schedule across all age groups.

How should the confidence interval be understood?

In general, a confidence interval conveys the statistical uncertainty around an estimated quantity, such as a response percentage. A narrower interval indicates greater precision under the method and assumptions used; a wider interval indicates less precision. The registry specifies a 95% confidence interval for the primary endpoint, but no interval or response estimate is reported. It is therefore not possible to assess the endpoint’s precision from the available record.

A confidence interval does not address every source of uncertainty. It does not, by itself, account for limitations such as selection into a per-protocol population, incomplete outcome measurement, or the lack of a control group. Those issues concern how the study was conducted and how broadly its results can be interpreted, not just the sampling uncertainty represented by an interval.

What does a single-arm design allow?

In general, a single-arm study summarizes outcomes observed among participants receiving one intervention. Without a concurrent control arm, it does not estimate a randomized between-group difference. Here, the registry describes one VARIVAX™ intervention and lists allocation as not applicable. The study can therefore be read as an evaluation of immunogenicity and safety in its enrolled participants, not as a direct comparative efficacy analysis.

Open-label means the study was not masked. For a laboratory outcome, the measurement method and threshold remain central to defining response, while the lack of masking is part of the design context. For safety outcomes, reporting and assessment may also be influenced by the open-label setting. The record does not report further procedures for blinded laboratory assessment or safety-event adjudication.

How should safety counts be read?

The safety summaries give age-group denominators at risk and counts affected. They report zero serious adverse events in the adult, adolescent, and both child groups. Separate counts are listed for other adverse events: 40 adults, 17 adolescents, 15 children aged 7 to 12 years, and 16 children aged 12 months to 6 years. In general, a count tells how many participants met the record’s event definition; it does not describe event duration, severity, recurrence, or causality unless those details are separately reported.

The registry also lists Headache, 3.0%, among its top serious terms. The relationship between that term listing and the age-group serious-event summaries is not specified in the record. No group attribution or further interpretation should be inferred from that listing alone.

General planning calculations based on an observed effect are not the same as observed trial outcomes or observed power. The registry describes sample-size assumptions for planning illustrations, including a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not describe this single-arm trial’s allocation, and the record does not report a formal hypothesis test. Planning illustrations should therefore be read as hypothetical design calculations, not as evidence that the study had a particular probability of detecting an effect.

What statistical details are not available?

The registry record does not report the primary result, the confidence interval, the method used to calculate that interval, or the handling of missing primary measurements. It also does not report interim analyses or a complete statistical analysis plan. These omissions prevent a fuller assessment of how the endpoint was analyzed and how robust the reported result would be; in this case, the endpoint result itself is not reported.

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("VARIVAX Adults (18 to 75 Years)", "VARIVAX™ Adolescents 13 to 17 Years of Age", "VARIVAX™ Children 7 to 12 Years of Age", "VARIVAX™ Children 12 Months to 6 Years of Age")
n      <- c(26, 18, 22, 34)
events <- c(26, 18, 21, 34)
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  VARIVAX Adults (18 to 75 Years)  26  26  100.0  86.8  100.0  87.1  100.0  87.2  99.9
ARM  VARIVAX™ Adolescents 13 to 17 Years of Age  18  18  100.0  81.5  100.0  82.4  100.0  82.4  99.9
ARM  VARIVAX™ Children 7 to 12 Years of Age  22  21  95.5  77.2  99.9  78.2  99.2  78.1  98.9
ARM  VARIVAX™ Children 12 Months to 6 Years of Age  34  34  100.0  89.7  100.0  89.8  100.0  90.0  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures and describes several secondary safety outcomes, including solicited and unsolicited injection-site adverse events, elevated temperature, and varicella- and herpes zoster-like rashes after each vaccination. However, the analysis count is zero, and the brief summary states that no formal hypothesis was tested. A multiplicity adjustment strategy, if any, is not reported in the registry record.

Multiplicity arises when several outcomes, time points, or subgroups are examined. In general, making many statistical comparisons can increase the chance of at least one apparently notable result occurring by chance if each is interpreted as a separate confirmatory test. This general concern does not establish that any particular result in this study is false; the record does not provide inferential results or a testing plan that would permit such an assessment.

The primary population is described as per-protocol participants who were seronegative at baseline and received the vaccination schedule relevant to their age group. The registry’s full description is incomplete, and the numbers included in the primary analysis are not reported in the registry record. The safety denominators are available by age group, but they should not be substituted for the primary endpoint denominators.

Missing-data rules, reasons for missing measurements, and sensitivity analyses are not reported in the registry record. In general, missing outcome data can affect an estimated response percentage if participants with missing assessments differ from those with observed measurements. Without the analysis rules and missingness details, the effect of missing data cannot be evaluated. The available information also does not establish whether any secondary outcome analyses were adjusted for multiplicity or whether subgroup analyses were prespecified.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: headache (3.0%).

The registry reports serious adverse-event counts and numbers at risk for each age group. Among adults aged 18 to 75 years, 0 of 50 participants were reported with a serious adverse event. Among adolescents aged 13 to 17 years, the count was 0 of 30. Among children aged 7 to 12 years, it was 1 of 33; among children aged 12 months to 6 years, it was 0 of 37. No deaths were reported in any of these groups.

These are counts observed in the study, not comparisons with another group. A zero count means no event of that category was recorded among the stated participants at risk; it does not establish that the event is impossible or that its underlying frequency is zero. The record does not provide further detail about event timing, duration, attribution, or the criteria used to classify events as serious.

The registry separately reports other adverse-event counts of 40 adults, 17 adolescents, 15 children aged 7 to 12 years, and 16 children aged 12 months to 6 years. It also lists Headache, 3.0%, among its top serious terms. The record does not explain how that term listing relates to the age-group serious-event counts, so no age-specific interpretation should be assigned to it.

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

The study’s design and endpoint definition make clear what the investigators intended to assess: a VZV antibody response among participants who were seronegative at baseline, measured with gpELISA at a specified time after the last scheduled dose. The response threshold was at least 5 gpELISA units/mL, with baseline titer <1.25 gpELISA units/mL. The record also describes safety monitoring in four age groups.

However, the primary response rate and its 95% confidence interval are not reported in the registry record. The central immunogenicity result therefore cannot be quantified or assessed for precision from the available information. The record’s statement that no formal hypothesis was tested also means the study should not be read as a reported formal test of a treatment effect.

The single-arm, open-label design supports description of outcomes observed among participants who received VARIVAX™. It does not provide a randomized comparison, so it cannot isolate a difference attributable to the intervention relative to another treatment or a control condition. The age-specific vaccination schedules also differ: children were assessed after Vaccination 1, while adults and adolescents were assessed after Vaccination 2.

The safety summaries document the reported serious-event counts, other adverse-event counts, and absence of deaths in the listed groups. Those summaries do not establish comparative safety, explain whether an event was caused by vaccination, or characterize unreported details such as event duration and recurrence. Zero serious events in most groups is an observation from the stated study denominators, not proof that serious events cannot occur.

Overall, the registry record supports an understanding of the study’s intended question, design, endpoint definition, and reported safety counts. It does not supply the primary immunogenicity estimate or enough statistical detail to reconstruct its analysis. Conclusions should therefore be limited to what the record documents, without treating missing results as evidence for or against a particular response.

14. Why This Trial Matters Statistically

This trial illustrates how an endpoint’s definition determines what a result would mean. The response rule combines a baseline seronegative criterion with a post-vaccination antibody threshold measured by a named laboratory assay. It also specifies different assessment points by age group, following the last scheduled vaccination. Those details are essential for interpreting any response percentage and for understanding which participants belong in the analysis denominator.

The single-arm design is another key statistical feature. It can describe outcomes in participants who received the intervention, but it cannot estimate a randomized contrast against a control group. This distinction helps separate an observed antibody response from a comparative treatment effect. The record’s statement that no formal hypothesis was tested further frames the trial as an evaluation rather than a documented confirmatory test.

The record also shows why result availability matters. It names a 95% confidence interval for the primary outcome but does not report the estimate or interval. Without those values, the endpoint’s magnitude and precision cannot be evaluated, even though the outcome definition and assessment schedule are clear. A named statistical measure is not a substitute for the numerical result needed to interpret it.

Finally, the safety information demonstrates the difference between counts and comparative evidence. Serious-event counts and other adverse-event counts describe observations in the study groups; they do not establish differences between interventions. The age-group denominators provide context for those counts, while the absence of a control group limits comparative interpretation. Together, these features make the record useful for understanding the design and reporting boundaries, even though the main immunogenicity result is not available.

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 primary limitation for interpreting immunogenicity is that the registry record does not report the primary response estimate or its 95% confidence interval. Although the outcome definition, assay, baseline criterion, and timing are described, the central numerical result is absent. The number included in the per-protocol primary analysis is also not reported in the registry record.

The study was single-arm and open-label, with no randomized control group. As a result, the record does not support a direct comparison with another intervention or a control condition. The study’s age groups also followed different vaccination schedules and assessment timings: children were assessed after one vaccination, while adults and adolescents were assessed after two. These distinctions should be retained when interpreting any age-specific results, if available elsewhere.

The primary population description is truncated, and details about protocol deviations, missing measurements, endpoint analysis methods, confidence-interval construction, and sensitivity analyses are not reported in the registry record. The record also does not report interim analyses or a complete statistical analysis plan. These gaps limit assessment of how participants entered the analysis, how incomplete data were handled, and how the endpoint estimate was obtained.

For safety, the record supplies age-group counts but not event timing, duration, recurrence, attribution, or the criteria used for seriousness. It lists Headache, 3.0%, among top serious terms without explaining the relationship between that listing and the group-level serious-event summaries. The reported counts therefore offer only a limited account of safety outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of the Immunogenicity and Safety of VARIVAX™ in Healthy Russians (V210-058) — NCT03843632.
• Registry record last updated 2021-04-06; status last verified 2021-03.
• Results first posted 2021-04-06.
• 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

NCT03843632 is a completed Phase 3, open-label, multicenter, single-arm study evaluating VARIVAX™ in healthy Russian participants aged 12 months and older. The registry lists enrollment of 150 and describes one subcutaneous dose on Day 1, with a second dose on Day 43 for adults and adolescents aged 13 years and older. Children were assessed 6 weeks after Vaccination 1; adults and adolescents were assessed 6 weeks after Vaccination 2.

The primary endpoint was the VZV antibody response rate among participants seronegative at baseline, using gpELISA and a response threshold of at least 5 gpELISA units/mL. The response estimate and 95% confidence interval are not reported in the registry record. The brief summary states that no formal hypothesis was tested.

The safety record reports zero deaths in each age group and serious adverse-event counts of 0 of 50 adults, 0 of 30 adolescents, 1 of 33 children aged 7 to 12 years, and 0 of 37 children aged 12 months to 6 years. Other adverse-event counts are also listed by group. The single-arm design permits descriptive interpretation, not a randomized comparison.