Safety and Immunogenicity of the Human Cytomegalovirus (CMV) Vaccine (V160) in Healthy Japanese Men (V160-003): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of the Human Cytomegalovirus (CMV) Vaccine (V160) in Healthy Japanese Men (V160-003) (NCT03840174), a randomized phase 1 study. The primary outcome is Percentage of Participants With a Solicited Injection-site Adverse Event (AE).

2. Clinical Question

This is a descriptive safety question in an early-phase study, not a confirmatory test of a treatment effect. The registry record reports endpoint percentages for each treatment and serostatus group, but does not report confidence intervals or a formal comparison. Those features matter when interpreting apparent differences: the percentages describe the observed groups, while the record does not establish how precise the estimates are or whether a planned inferential test was conducted.

3. Trial Design

The registry identifies NCT03840174 as a Phase I randomized, double-blind, placebo-controlled, parallel-group study. It evaluated V160 in healthy Japanese men and was sponsored by Merck Sharp & Dohme LLC. The record lists the study as completed, with a start date of 2019-03-08 and a primary completion date of 2019-11-07.

Participants were assigned to V160 or placebo, and each intervention was scheduled for intramuscular administration on Day 1, Month 2, and Month 6. The registry describes masking as triple. It does not explain which parties were masked or provide further detail about the masking procedures; those details are not reported in the registry record.

For the primary endpoint, results are split into four groups: V160 recipients who were CMV seronegative at baseline, V160 recipients who were seropositive, placebo recipients who were seronegative, and placebo recipients who were seropositive. The reported group sizes are 6, 6, 3, and 3, respectively. Keeping serostatus groups separate preserves the distinction the registry makes in its study purpose and reporting. It also means that a comparison within one serostatus stratum is not interchangeable with a comparison that pools participants across strata.

The primary endpoint population is described as all randomized participants who received at least 1 vaccination. The enrollment figure is 18, but the record does not provide a participant-flow account or explain whether anyone was excluded from the endpoint population. A detailed protocol, allocation procedure, and statistical analysis plan are not reported in the registry record. The study description explicitly says there was no formal hypothesis, so it should not be read as a trial designed around a stated confirmatory hypothesis test.

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: All randomized participants who received at least 1 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 Percentage of Participants With a Solicited Injection-site Adverse Event (AE), measured over Up to 5 days after each vaccination.

The primary endpoint is the percentage of participants with a solicited injection-site adverse event up to 5 days after each vaccination. The specified events are pain or tenderness, erythema or redness, and swelling. Participants used a vaccination report card to document whether these events occurred.

A percentage is a binary-outcome summary: each participant is classified according to whether the endpoint event was reported, and the result expresses the proportion meeting that definition. In this study, the posted percentages are given separately for the V160 and placebo groups within each baseline CMV serostatus category. The registry identifies the endpoint population as randomized participants who received at least 1 vaccination.

Solicited events are used in safety monitoring because asking about specified symptoms within a defined observation period can capture events of particular interest consistently. That general rationale does not establish that every event was recorded or that the measure captures all possible harms. This endpoint concerns injection-site events; it is not a comprehensive measure of overall safety, and it does not itself assess immune response or vaccine efficacy.

The phrase “after each vaccination” defines the observation window for the endpoint. The registry record does not describe in detail how repeated reports across vaccination visits were combined into the participant-level percentage. That reporting detail is therefore not reported in the registry record and should not be inferred from the percentages alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage represent?

For a binary endpoint, the outcome for each participant is classified as present or absent according to the endpoint definition. A percentage then describes how common the event was in the group being summarized. Here, the event is a solicited injection-site adverse event within the stated observation period. The posted percentages are group summaries, not measurements of severity, duration, or the number of separate symptoms a participant experienced.

Because the endpoint definition includes more than one symptom, the participant-level result concerns whether a qualifying event was reported. The registry record says participants documented pain or tenderness, erythema or redness, and swelling on a vaccination report card. It does not specify in the endpoint description how multiple symptoms or reports across doses were handled when producing the final percentage. That detail is not reported in the registry record.

Why are results separated by serostatus?

The study purpose and results distinguish baseline CMV-seronegative from baseline CMV-seropositive participants. Reporting the groups separately makes the denominators and observed percentages specific to each category. A within-category description answers a different question from a pooled summary. Pooling or adjusting across the categories would require an analysis choice, and the record does not describe such an analysis for this endpoint.

The four groups also differ in size. In general, percentages calculated from smaller groups are more sensitive to the outcome status of individual participants than percentages from larger groups. That is one reason descriptive percentages should be accompanied by uncertainty measures when available. Confidence intervals are not reported for these primary endpoint results in the registry record.

What would a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified method and assumptions. It can show a range of values compatible with the observed data and method, rather than presenting a point estimate alone. It does not guarantee that the true value lies in the interval, and it does not remedy limitations in study design, population size, or measurement.

No confidence interval is reported for the posted injection-site percentages. Therefore, the reader cannot use the registry results to assess the interval-based precision of each group estimate or of a treatment contrast. The absence of an interval should not be replaced by an interval calculated from assumptions that are not part of the posted analysis.

Why is there no recalculated comparison?

The registry analysis information indicates that values are missing or not estimable for a two-arm comparison of this binary-percentage endpoint. As a result, there is no recalculated unadjusted comparison to present alongside the sponsor’s analysis. The displayed endpoint percentages remain descriptive group results; subtracting or otherwise transforming them would create a new calculation not reported in the record.

In general, a statistical comparison for a binary endpoint depends on the chosen estimand, method, handling of the groups, and assumptions. Small group sizes can make estimates and tests especially sensitive to individual observations. The registry record does not state a formal hypothesis, a test method, an adjustment strategy, or an inferential result for this endpoint. Those methods are not reported in the registry record.

How should planning calculations be distinguished from trial results?

Any sample-size values associated with planning illustrations answer a hypothetical design question: how many participants per arm might be needed under stated assumptions to detect a selected effect with a chosen power. Such illustrations are not observations from this trial, do not establish the study’s original design rationale, and are not “observed power.” The record does not report a formal hypothesis or a sample-size justification, so no planning illustration should be treated as evidence that the trial was sized for a particular confirmatory objective.

More generally, power calculations depend on assumed event rates, an effect to detect, a significance level, allocation, and a statistical model. A planning exercise based on an observed effect can be informative as an illustration but is especially dependent on that observed estimate. It cannot turn a descriptive result from small groups into a definitive treatment comparison. The assumptions described for planning illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the illustrations are not the trial’s own design documentation.

The study’s randomized, double-blind, placebo-controlled, parallel-group design describes its broad structure. General statistical reasoning recognizes that random assignment can support comparisons when appropriately analyzed, while masking can reduce some forms of bias. Those design features do not guarantee balance in small groups, remove uncertainty, or establish the details of the analysis. Procedures for allocation, missing outcomes, and the statistical model 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("V160: CMV Seronegative at Baseline", "V160: CMV Seropositive at Baseline", "Placebo: CMV Seronegative at Baseline", "Placebo: CMV Seropositive at Baseline")
n      <- c(6, 6, 3, 3)
events <- c(6, 5, 0, 1)
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  V160: CMV Seronegative at Baseline  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  V160: CMV Seropositive at Baseline  6  5  83.3  35.9  99.6  43.6  97.0  42.1  96.3
ARM  Placebo: CMV Seronegative at Baseline  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Placebo: CMV Seropositive at Baseline  3  1  33.3  0.8  90.6  6.1  79.2  6.8  80.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 7 outcome measures, including 4 secondary outcomes. The secondary outcomes named include CMV-specific neutralizing antibody geometric mean titer and measures of viral detection in plasma, urine, saliva, injection-site swabs, and adhesive tape swabs. The record reports 1 analysis, but the statistical plan and the relationship between that analysis and the full set of outcomes are not described in the information. Numerical results for the secondary outcomes are not reported in the registry record.

When a study examines multiple outcomes or multiple comparisons, general statistical practice considers whether the chance of false-positive findings should be controlled and how the outcomes relate to the study’s objectives. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a prespecified strategy for interpreting multiple results. The brief summary states there was no formal hypothesis. Consequently, the listed outcomes should not be treated as a set of confirmatory tests with a known family-wise error strategy.

The primary endpoint population is described as randomized participants who received at least 1 vaccination. A detailed account of missing endpoint observations, exclusions, withdrawals, or how missing reports were handled is not reported in the registry record. The record also does not provide a participant-flow narrative that would clarify whether all randomized participants contributed to the primary endpoint population.

These gaps do not establish that observations were missing or that any particular handling method was used. They mean that the reader cannot evaluate the effect of missing data or verify analysis-population decisions from the registry record. The stated endpoint population should be distinguished from the enrollment figure, and the group percentages should be interpreted according to the populations and denominators explicitly reported.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event summary reports zero serious adverse events and zero deaths in each of the four treatment-by-serostatus groups. These figures are separate from the primary endpoint, which concerns solicited injection-site events. A zero count in a group means no serious adverse event or death was recorded in that group in the posted summary; it does not establish that the risk is absent.

The adverse-event summary also lists participants with other adverse events, which are not the same category as serious adverse events. Those entries should not be relabeled as serious events, nor do the registry entries provided define them as a complete measure of all non-serious safety outcomes. The primary endpoint percentages concern specified local symptoms after vaccination, while the serious-event summary covers a distinct safety category.

Serious adverse events are uncommon outcomes in many settings, and general interpretation of zero observed events depends on the amount of observation and the size of the group. With the small groups reported in this study, the absence of a recorded serious event cannot rule out events that might occur in a larger or different population. The registry record does not provide a confidence interval for these serious-event figures or detail the duration of safety follow-up in this summary.

Accordingly, the serious-event results are best read as counts recorded in this study, not as a guarantee of safety or an estimate that applies broadly beyond the reported groups.

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

The results describe a narrow question: the percentage of participants who reported a specified injection-site event after vaccination, within a Phase I study of healthy Japanese men. The registry presents the endpoint separately for V160 and placebo and by baseline CMV serostatus. This is useful descriptive information about the groups enrolled and the endpoint definition used.

The percentages do not establish whether V160 caused more or fewer injection-site events than placebo. The study description states that there was no formal hypothesis, the group sizes are small, and no confidence intervals or formal comparison are reported. The registry analysis information also indicates that a two-arm comparison was missing or not estimable. The percentages therefore should not be recast as a statistically established difference.

Nor does this endpoint answer whether V160 produced an immune response or prevented CMV infection. The registry lists immunogenicity and viral-detection outcomes, but their numerical results are not reported in the registry record summarized for this analysis. An injection-site safety measure cannot stand in for those distinct outcomes. Likewise, the record’s serious-adverse-event figures do not establish that uncommon harms are impossible.

General interpretation of an early-phase trial distinguishes a description of observed participants from a conclusion about a broader population. Randomization and masking are important features of the design, but they do not remove the uncertainty associated with small groups or supply missing analysis details. The registry does not report a sample-size justification, formal statistical plan, or detailed missing-data handling for this endpoint.

The reasonable statistical conclusion is limited: the posted results report the observed injection-site event percentages in four small groups defined by treatment and baseline CMV serostatus. They provide a record of these observations, but not a precise or confirmatory estimate of a treatment effect, an immunogenicity conclusion, or a population-wide safety conclusion.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how early-phase safety results can be presented by both intervention and a baseline characteristic. The separation by CMV serostatus preserves a feature that is central to the study description, rather than concealing it in an overall percentage. It also makes clear that each reported estimate belongs to a specific subgroup and has its own denominator.

The study illustrates why percentages require context. A value such as 100.0% or 0.0% can appear definitive when read without its group size, but the reported groups are small. General statistical reasoning cautions that estimates from small groups can be strongly affected by individual outcomes. Without confidence intervals or a reported comparison, the reader cannot judge precision using the registry results alone.

It also matters that the brief summary says there was no formal hypothesis. The primary endpoint can still be described, and its event definition can still be useful, but the record should not be interpreted as if it reports a confirmatory test. Separating descriptive results from inferential claims is especially important when multiple outcomes are listed and the registry does not state a multiplicity strategy.

Finally, the endpoint’s scope is explicit: it concerns solicited injection-site events over the stated period. It is distinct from serious adverse events, immunogenicity, and viral detection. Keeping those outcome types separate helps avoid drawing conclusions that the reported endpoint cannot support. The registry record contributes a bounded description of a Phase I study, not a comprehensive answer to every safety or immune-response question about V160.

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 endpoint groups are small, with reported sizes of 6, 6, 3, and 3. The registry does not provide confidence intervals for the percentages, so the precision of the group estimates cannot be assessed from the posted results. The record also does not provide an estimable two-arm comparison for this binary endpoint.

The outcome is based on participant documentation using a vaccination report card and covers solicited pain or tenderness, erythema or redness, and swelling. The registry does not explain how reports from different vaccination visits were combined into the final participant-level percentage. It also does not report the completeness of report-card data or the handling of missing observations.

Results are stratified by baseline serostatus, but the record does not report a pooled analysis, adjustment for serostatus, or an interaction analysis. The study description states that there was no formal hypothesis, and a detailed statistical analysis plan, sample-size justification, and multiplicity approach are not reported in the registry record.

The study population is described as healthy Japanese men, which limits how directly the descriptive results speak to populations outside that group. The primary endpoint concerns solicited local events and does not measure every aspect of safety. The record’s zero serious-event and death counts are observations in small groups and do not rule out uncommon events. Numerical findings for the listed secondary immunogenicity and viral-detection outcomes are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of the Human Cytomegalovirus (CMV) Vaccine (V160) in Healthy Japanese Men (V160-003) — NCT03840174.
• Registry record last updated 2023-05-06; status last verified 2023-05.
• Results first posted 2021-11-15.
• 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

NCT03840174 is a completed Phase I randomized, double-blind, placebo-controlled, parallel-group study of V160 in healthy Japanese men. The registry lists enrollment of 18 and study dates from 2019-03-08 to primary completion on 2019-11-07. V160 and placebo were each scheduled for intramuscular administration on Day 1, Month 2, and Month 6.

The primary endpoint was the percentage of participants with a solicited injection-site adverse event up to 5 days after each vaccination. The registry reports percentages by treatment and baseline CMV serostatus, with group sizes of 6, 6, 3, and 3. The study summary states that there was no formal hypothesis. Confidence intervals, a formal comparison, detailed missing-data handling, and a full statistical plan are not reported in the registry record.

The results are descriptive and specific to the reported endpoint and groups. They should not be interpreted as a confirmatory treatment-effect estimate or as a conclusion about the secondary immunogenicity outcomes, whose numerical findings are not reported in the registry record summarized for this analysis.