A Study on the Reactogenicity, Safety and Immune Response of a Targeted Immunotherapy Against HSV in Healthy Japanese Participants Aged 18-40 Years: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on the Reactogenicity, Safety and Immune Response of a Targeted Immunotherapy Against HSV in Healthy Japanese Participants Aged 18-40 Years (NCT05989672), a randomized phase 1 study. The primary outcome is Number of Participants Reporting Any Solicited Administration Site Events.

2. Clinical Question

This is principally a short-term reactogenicity question: it concerns the occurrence of specified local events after vaccination, rather than their severity or duration. The endpoint is a participant count, so its interpretation depends on how many exposed participants in each group had the required post-vaccination data and on the registry's event definition.

The study also set out to evaluate safety and immune response. Listed secondary outcomes include anti-HSVTI antibody seropositivity and geometric mean concentration, HSVTI-specific CD4+ and CD8+ T-cell frequencies, and reports of medical events, serious adverse events and potential immune-mediated conditions. These outcomes broaden the questions addressed by the protocol, but the registry record does not report results for the primary endpoint or analyses comparing the groups.

3. Trial Design

The registry describes a Phase 1, randomized, observer-blind, placebo-controlled study with a parallel-group model and quadruple masking. Its official title identifies the participants as HSV-2 seronegative Japanese adults aged 18-40 years. The study condition is herpes simplex, and its stated purpose is to evaluate reactogenicity, safety and immunogenicity of two HSV-targeted immunotherapy formulations. The registry lists GlaxoSmithKline as sponsor.

There were three intervention groups: HSVTI Formulation 1, HSVTI Formulation 2 and placebo. The arm descriptions call Formulation 1 high dose and Formulation 2 low dose. Participants received their assigned intervention at Day 1 and Day 29. The record gives an enrollment of 50. The at-risk counts shown with the posted adverse-event figures are 20 for Formulation 1, 20 for Formulation 2 and 10 for placebo; these figures describe those safety summaries, not necessarily every analysis population.

The registry gives the study start as 2023-08-08, primary completion as 2023-11-29, and status as completed. The primary endpoint concerns solicited administration site events following vaccination at Day 1, within the stated 7-day timeframe. The record also lists 23 outcome measures, including immune-response and safety outcomes.

Random allocation and masking are design features intended to reduce bias in comparisons, but the registry entry does not describe how the random sequence was generated, which roles were masked, or how allocation concealment was implemented. These details are not reported in the registry record. The record likewise does not describe a statistical analysis plan or report an inferential comparison of the groups. Consequently, the design can be characterized from the registry, but the effectiveness of its bias-control procedures and the precision of treatment comparisons cannot be assessed from the posted information.

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: Analysis was performed on the Exposed set (ES), which included all participants who received at least one dose of the study intervention and have post-vaccination data for the specified analysis at specified timepoints.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting Any Solicited Administration Site Events, measured over During the 7 days (including the day of vaccination) following vaccination at Day 1.

The primary endpoint is the number of participants reporting any solicited administration site event during the 7 days (including the day of vaccination) following vaccination at Day 1. The record names erythema (redness), pain and swelling as the solicited events. A participant counts as having an event if any listed symptom occurred, regardless of intensity grade. The measure is therefore a participant count, not a count of every symptom occurrence or a summary of symptom severity.

This endpoint is used to describe local reactogenicity after vaccination. A defined set of solicited symptoms and a specified observation window make the outcome more focused than an open-ended report of any health event. Counting participants with at least one event can also make the result straightforward to interpret, although it does not show which symptom occurred, how often symptoms occurred, or how intense or long-lasting they were.

The timing matters: the endpoint refers to the period following vaccination at Day 1, rather than an overall tally across both scheduled administrations. The record defines the analysis population as the Exposed set, comprising participants who received at least one dose and had post-vaccination data for the specified analysis at specified timepoints. The primary endpoint result, group-specific event counts, and any comparison estimates are not reported in the registry record. Without those results, the endpoint definition alone cannot establish how frequently events occurred or how groups differed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome in substance: a participant either reported at least one solicited administration site event within the defined observation window or did not. The registry describes the reported quantity as a number of participants, not a rate per exposure time. The listed symptoms are erythema (redness), pain and swelling, and any occurrence qualifies regardless of intensity grade. This definition should guide interpretation: it does not encode symptom severity, duration, or the number of distinct symptoms experienced by each participant.

In a trial with available group results, a basic description would report the number of participants with an event and the number assessed in each group. A comparison could then express the difference in observed event proportions or use another prespecified measure. Those are general statistical approaches, not results from this trial. The registry record does not report the primary endpoint counts, a chosen effect measure, or a model for comparing the randomized groups. No such comparison should be reconstructed from unrelated safety counts.

For a binary outcome, uncertainty depends on the observed event information and the number of participants contributing data. A confidence interval is a range of values that reflects sampling uncertainty under the method used; it is not a guarantee that the true value lies within the interval. If intervals for group estimates or a treatment contrast were reported, they would help show how precisely the data distinguish among plausible values. No primary endpoint confidence interval is reported in the registry record, so precision for that result cannot be judged.

Randomization is a design method for making assigned groups comparable in expectation, while masking can reduce the influence of knowledge of assignment on care, reporting or assessment. These are general purposes of trial design features. The record labels the study randomized, observer-blind and quadruple-masked, but does not explain the sequence-generation method, allocation concealment, identities of masked roles, or maintenance of masking. The labels alone do not document how these procedures operated.

The analysis population stated for the primary endpoint is the Exposed set. It includes participants who received at least one dose and had post-vaccination data for the specified analysis at specified timepoints. This differs conceptually from an analysis retaining every randomized participant regardless of exposure or data availability. Excluding participants without the necessary post-vaccination data can affect interpretation if their missingness is related to their symptoms or assigned group. The record does not report how many participants contributed to the primary analysis, whether endpoint data were missing, or how missing observations were handled.

The registry lists secondary immune outcomes such as antibody seropositivity, antibody geometric mean concentration, and geometric mean frequencies of HSVTI-specific CD4+ and CD8+ T cells. A geometric mean summarizes positive measurements on a multiplicative scale and is often used when values are skewed; this is general statistical context, not a description of the actual analysis used in this trial. The record does not give the results, analysis methods, transformations, handling of values below assay limits, or uncertainty estimates for these outcomes. Those details are not reported in the registry record.

Multiple outcomes raise a general interpretive issue: when many hypotheses are examined, the chance of at least one apparently notable finding can increase unless the analysis plan addresses multiplicity. The registry lists 23 outcome measures, but does not report a multiplicity adjustment or identify a hierarchy among outcomes. It is therefore not possible to determine from the record how results across endpoints were intended to be interpreted together. This does not establish that no such plan existed; it means that it is not reported in the registry record.

Over-dispersion is a general concern for count outcomes when the observed variability exceeds what a simple probability model assumes. It can affect standard errors and intervals if the model does not accommodate that extra variation. The primary endpoint is a count of participants with an event, rather than a recurrent-event count per participant, and the registry record does not specify a model or report a dispersion assessment. No claim about over-dispersion in this study can therefore be made.

The registry's primary outcome entry notes several categories or time points and does not reduce the endpoint to one comparison. This prevents a single unadjusted re-calculation from posted summary statistics: no relevant primary endpoint summaries are reported, and no sponsor analysis for that endpoint is posted. If recalculated summaries were ever presented, they would be simple unadjusted calculations from posted statistics, not substitutes for a sponsor's own analysis; where a discrepancy exists, the sponsor's own analysis takes precedence.

Any sample-size illustration based on an observed effect is a planning scenario, not observed power and not evidence that a hypothesis was confirmed. Such an illustration cannot reveal the original design rationale or sample-size justification unless the registry reports those details. The statistical plan and the rationale for the enrollment target are not reported in the registry record. The sample-size assumptions described for planning do not establish what analyses were prespecified or performed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 23 outcome measures spanning reactogenicity, antibody responses, T-cell responses and safety. It also lists 0 analyses. The posted record does not identify a primary-versus-secondary testing hierarchy beyond naming the primary endpoint, nor does it describe a multiplicity adjustment. When several outcomes are assessed, multiplicity matters because examining many results can make isolated patterns harder to distinguish from chance variation. This is general context; without an analysis plan or posted results, the approach used for this study cannot be assessed.

The primary endpoint population is the Exposed set, defined as participants who received at least one dose and had post-vaccination data for the specified analysis at specified timepoints. The record does not report the number with endpoint data, the amount or pattern of missing data, exclusions from the analysis, or any imputation or sensitivity analysis. Missingness can affect a result if the probability of data being absent is related to group assignment or outcome status; that is a general concern, not a finding about this trial.

The registry does not describe an intention-to-treat analysis, an alternative analysis population, or a method for handling missing observations. Those methods are not reported in the registry record. It is therefore not possible to determine whether the posted design and endpoint definition were paired with a prespecified missing-data strategy, or how robust any unposted findings might be to different assumptions. The absence of posted analyses should not be interpreted as a null result.

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 non-serious adverse event terms

The posted serious adverse-event summary lists 0 affected participants in HSVTI F1, 0 in HSVTI F2 and 0 in the placebo group. The corresponding at-risk counts are 20, 20 and 10. Deaths are listed as 0 in all three groups, and the record lists no top serious terms. These figures describe what is posted for the serious-event summary; they are not the primary endpoint counts.

A zero count in a study group means that no affected participant is listed in that summary for that group. It does not demonstrate that the underlying risk is zero, and it does not exclude events that were not captured or reported. The counts also do not provide an interval estimate or a formal comparison between groups. With no serious events listed, a comparative estimate based on those events is not reported in the registry record.

The serious-event summary should also be distinguished from the broader safety and reactogenicity questions. Solicited administration site events include redness, pain and swelling and are assessed over a defined post-vaccination window. The posted serious-event figures do not answer how many participants experienced those solicited symptoms, their intensity, or other non-serious events. The registry's full safety interpretation is limited by the absence of posted analyses and additional details on event ascertainment and missing data.

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

The record establishes that this was a completed, randomized, placebo-controlled Phase 1 study of two HSV-targeted immunotherapy formulations in HSV-2 seronegative Japanese adults aged 18-40 years. It documents the intervention schedule, the primary reactogenicity endpoint, several secondary immune and safety outcomes, and serious adverse-event summary counts. These design and outcome descriptions clarify what the study was intended to examine.

It does not establish the observed frequency of the primary solicited administration site events. The registry record does not report primary endpoint results, group comparisons, confidence intervals or p-values. Nor does it report the listed immune-response results or analyses of the secondary safety outcomes. The serious adverse-event counts are posted, but they are a separate summary and cannot stand in for the missing primary endpoint results or the broader safety analyses.

Consequently, the posted information does not show whether the formulations differed from placebo in local reactogenicity, whether antibody or T-cell measures changed, or how precisely any such differences were estimated. It also does not establish that no events occurred beyond the serious events listed. An unreported result is not equivalent to a result of zero or to evidence of no difference.

In general, a clinical trial's findings are interpreted by considering the outcome definitions, the analysis population, the amount of missing data, the estimates and their uncertainty, and the planned analysis. Here, the endpoint definitions and some design features are available, but the primary results and key statistical details are not. Any conclusion about comparative effects would go beyond what the registry record reports.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly described trial design and a reported analysis. The registry identifies randomized parallel groups, masking, a placebo comparator, an exposed analysis population and a specific primary reactogenicity endpoint. These details establish the intended structure of the comparison and the meaning of the outcome.

At the same time, a defined endpoint is not itself a result. Without participant counts for the primary outcome, an effect estimate and a measure of uncertainty, readers cannot assess either the observed pattern or its precision. This distinction is central when using registry records: design descriptions indicate what investigators planned to evaluate, while results are needed to characterize what the observed data show.

The entry also illustrates why analysis populations and multiplicity matter. The primary analysis population requires exposure and post-vaccination data, while the registry lists a range of immune and safety outcomes. Evaluating those features requires details on missing observations, analysis choices and the treatment of multiple outcomes. Those details are not reported in the registry record.

The posted serious adverse-event counts provide limited safety information, but they do not answer the primary local-event question or replace a full comparative safety analysis. Keeping endpoints distinct prevents a safety summary from being mistaken for a reactogenicity finding. In this record, the most defensible statistical reading is therefore a careful account of what is specified, what safety counts are posted, and which outcome analyses remain unreported.

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 central limitation for interpreting the trial statistically is that the primary endpoint result is not reported in the registry record. The record provides neither group-specific counts for solicited administration site events nor a comparison estimate, confidence interval or p-value. The registry also notes that the primary outcome has several categories or time points and is not reduced to one comparison, limiting any attempt to summarize it as a single contrast.

The analysis population is described, but the number of participants with primary endpoint data is not reported. The record does not state how many observations were missing, why data may have been unavailable, or how missingness was handled. Without this information, the completeness of the endpoint data and the potential effect of exclusions cannot be assessed.

The registry lists 23 outcome measures and 0 analyses. It does not report the statistical analysis plan, the analysis methods used for the immune outcomes, how multiplicity was handled, or a sample-size justification. The labels for randomization and masking are present, but implementation details are not reported in the registry record. These gaps limit assessment of prespecification, bias control and statistical precision.

The posted serious-event figures are limited to the affected and at-risk counts, deaths, and top serious terms. They do not provide detailed event timing, duration, severity, or inferential comparisons. Those figures cannot be generalized to all safety outcomes or substituted for the missing primary endpoint results. These limitations concern the available registry information and should not be read as findings about unreported outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study on the Reactogenicity, Safety and Immune Response of a Targeted Immunotherapy Against HSV in Healthy Japanese Participants Aged 18-40 Years — NCT05989672.
• Registry record last updated 2025-06-12; status last verified 2025-06.
• Results first posted 2025-06-12.
• 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

The registry describes a completed Phase 1 randomized, observer-blind, placebo-controlled parallel-group study of HSV-targeted immunotherapy in HSV-2 seronegative Japanese adults aged 18-40 years. It lists two formulations and placebo, administered at Day 1 and Day 29, and gives an enrollment of 50.

The primary endpoint is the number of participants reporting any solicited administration site event during the 7 days (including the day of vaccination) following vaccination at Day 1. The registry lists 23 outcome measures and 0 analyses. Primary endpoint results and comparative analyses are not reported in the registry record.

The posted serious adverse-event summary lists 0 affected participants in each group, with at-risk counts of 20 for HSVTI F1, 20 for HSVTI F2 and 10 for placebo. No top serious terms are listed. These safety figures do not supply the missing primary reactogenicity results.