Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-028): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-028) (NCT03848065), a randomized phase 1 study. The primary outcome is Percentage of Participants With a Solicited Injection-site Adverse Event (AE).

2. Clinical Question

The trial was designed to evaluate safety, tolerability, and immunogenicity of V114 in this population. The primary endpoint addresses a specific, actively solicited aspect of short-term local reactogenicity. It does not by itself summarize all adverse events, serious events, or immune responses. The record lists secondary immune outcomes, including serotype-specific IgG thresholds and concentrations, as well as responses to DTaP-IPV. Those broader outcomes address different questions from the primary injection-site endpoint.

3. Trial Design

This was a Phase I, randomized, multicenter, parallel-group trial in healthy Japanese infants. The registry record classifies the masking as triple; the official title describes the trial as double-blind. It lists enrollment as 133 and status as completed. The study began on 2019-04-02, with primary completion on 2020-06-24.

The three named groups were V114-SC, V114-IM, and PCV13-SC. The planned schedules described V114 or PCV13 at visits around 3, 4, 5, and 12 to 15 months of age. DTaP-IPV was included as a concomitant study vaccine. The V114-IM description specifically says it was administered at the same time as V114-IM. The descriptions for the V114-SC and PCV13-SC arms are truncated in the registry record, so details beyond their visible text are not reported in the registry record.

The endpoint population included randomized participants who received at least one trial-vaccine dose. This is narrower than an analysis of everyone randomized: participants who did not receive a dose would not meet the stated population definition. The record does not report further details about randomization procedures, allocation concealment, masking procedures, or the number of participants analyzed in each arm.

The primary endpoint focused on solicited injection-site events during the specified period after vaccination. Secondary outcomes concerned immune responses to pneumococcal serotypes and protective responses to DTaP-IPV. These outcomes differ in measurement and interpretation, so the primary safety question should not be treated as a substitute for the immunogenicity assessments.

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 population consisted of all randomized participants who received at least one dose of trial vaccine.

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 Day 1 to Day 14 post each vaccination.

The primary endpoint is the percentage of participants with a solicited injection-site adverse event from Day 1 to Day 14 after each vaccination. The record defines the solicited events as injection-site erythema (redness), induration (a hard lump), pain, and swelling. It defines an adverse event broadly as an untoward medical occurrence temporally associated with study treatment, whether or not considered related to treatment.

A percentage expresses how common an event was in the population being assessed. For a solicited endpoint, events are actively sought according to a specified list rather than limited to events that participants happen to mention spontaneously. This can make the outcome more structured and consistent, while still depending on how events are collected and recorded. The timeframe specifies the post-vaccination period included in the endpoint; it does not describe longer-term safety.

Injection-site events are relevant to a trial comparing vaccine products or routes because they capture local reactions following administration. However, this endpoint does not measure every kind of adverse event, establish whether an event was caused by vaccination, or summarize immune response. The registry record does not report the primary endpoint percentages or a statistical comparison, so the relative frequency of these solicited events across arms cannot be described from the recorded results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint measure?

The primary outcome is binary at the participant level: a participant either met the endpoint definition by having at least one specified solicited injection-site adverse event in the assessment period, or did not. The endpoint is reported as a percentage of participants. The listed event types are redness, induration, pain, and swelling. The specified period is Day 1 to Day 14 post each vaccination.

General statistical explanation: binary outcomes are often summarized by the number of participants meeting the definition and the denominator assessed, then expressed as a percentage. The denominator matters because a percentage is meaningful only in relation to the population from which it was calculated. The registry record describes the primary analysis population as randomized participants who received at least one dose of trial vaccine, but primary endpoint denominators and percentages are not reported in the registry record.

Why does endpoint definition matter?

A solicited event is collected through active assessment of a prespecified symptom list. This differs from an unsolicited event, which is not defined by the same checklist. Standardized collection can make assessments more comparable, but interpretation still depends on how symptoms were elicited, recorded, and handled when data were missing. Those collection details are not reported in the registry record. The broad adverse-event definition also does not imply that an event was caused by the vaccine; it includes events temporally associated with study treatment whether or not considered related.

What can a comparison show?

General statistical explanation: a between-group comparison estimates how the outcome differs between groups under the chosen analysis. The estimate should be considered alongside its uncertainty, commonly expressed with a confidence interval. A confidence interval describes a range of values compatible with the data and statistical assumptions; it does not establish causality or clinical importance by itself. No primary endpoint comparison estimate or confidence interval is reported in the registry record. The record notes that the primary outcome has several categories or time points and was not reduced to one comparison.

How should multiple outcomes be considered?

The registry lists 6 outcome measures and 135 analyses. When many outcomes, time points, or comparisons are assessed, the chance of obtaining apparently notable results by chance can increase. General statistical approaches may address this through prespecified outcome hierarchies or adjustment for multiple testing, but the registry record does not report whether such an approach was used. The analysis count alone does not reveal which analyses were prespecified, how they were related, or whether any multiplicity adjustment was applied.

What do the planning assumptions mean?

The registry record describes a sample-size planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. For time-to-event outcomes, the record says the illustration uses a total number of events; other illustrations use participants per arm. The actual sample-size values and the exact effect fractions are not reported in the registry record in the registry record for this analysis.

General statistical explanation: a planning calculation asks what amount of information might be needed to detect an assumed effect under specified conditions. Observed power, calculated after a study from its estimated effect, is generally not a substitute for examining the estimate and its uncertainty. Planning assumptions should not be mistaken for the trial’s actual analysis plan. The registry record does not report the trial’s sample-size justification, its statistical analysis plan, or whether interim analyses were conducted.

How should the immune outcomes be distinguished?

The listed secondary immunogenicity outcomes include the percentage meeting the serotype-specific IgG threshold of ≥0.35 µg/mL and serotype-specific IgG geometric mean concentrations. A threshold percentage describes the share meeting a defined cut point; a geometric mean concentration summarizes concentration measurements on a multiplicative scale. The record also lists protective-response thresholds for DTaP-IPV antigens. These outcome types answer different questions and require outcome-specific definitions and analysis methods. Their results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 6 outcome measures and 135 analyses. That is a substantial set of assessments relative to the single primary endpoint named in the record, but the counts alone do not establish that the analyses were exploratory or that the trial’s conclusions were affected by multiplicity. The record does not report which analyses were prespecified, whether outcomes were prioritized in a hierarchy, or whether statistical adjustments were used to account for multiple comparisons.

General statistical explanation: when many hypotheses are tested, some results may appear statistically notable by chance even if there is no corresponding underlying effect. A prespecified analysis plan and transparent reporting help readers distinguish primary confirmatory questions from additional analyses. The registry record does not report a detailed statistical analysis plan, interim analyses, or a multiplicity-control strategy.

Missing-data handling is also not reported in the registry record. The stated primary analysis population consists of randomized participants who received at least one dose. The record does not explain how missing endpoint assessments, incomplete follow-up, withdrawals, or participants with no usable outcome data were handled. It does not report the extent or pattern of missing data.

These omissions matter because the percentage for a binary endpoint depends on who is included in the denominator and how unavailable assessments are treated. The stated population definition provides some context, but it is not enough to reconstruct the analysis. Without the analysis population counts, missing-data procedures, and outcome estimates, the primary endpoint’s precision and susceptibility to incomplete follow-up cannot be assessed from the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hand-foot-and-mouth disease (2.3%), respiratory syncytial virus infection (2.3%), cardio-respiratory arrest (2.2%), pneumonia respiratory syncytial viral (2.2%).

The registry record lists serious adverse-event counts by group alongside counts at risk. For V114-SC, it records 1 serious adverse event among 44 at risk; for V114-IM, 3 among 45; and for PCV13-SC, 2 among 43. These are descriptive counts and denominators, not evidence that an event was caused by a vaccine. The record does not report a statistical comparison of serious adverse events between groups.

Deaths are listed as 0 for V114-SC, 1 for V114-IM, and 0 for PCV13-SC. The record does not provide a causal attribution for the death, and the counts should not be interpreted as establishing a treatment relationship. A serious event and a death are distinct safety summaries; the record’s serious-event counts should not be added to, or treated as equivalent to, death counts.

The listed serious-event terms include hand-foot-and-mouth disease and respiratory syncytial virus infection at 2.3% each, and cardio-respiratory arrest and pneumonia respiratory syncytial viral at 2.2% each. The registry record does not identify an arm for these term-specific percentages in the information. The figures therefore should not be used to compare groups. Serious-event counts and term listings do not replace the missing primary solicited injection-site outcome percentages.

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

The record identifies a randomized Phase I study of V114 administered by two routes in healthy Japanese infants, with a PCV13-SC group. It describes safety, tolerability, and immunogenicity as the study’s aims. The primary endpoint is clearly defined as the percentage of participants with a solicited injection-site adverse event during Day 1 to Day 14 after each vaccination. These details establish what the primary safety question was intended to assess.

The record does not report the primary endpoint percentages or a single comparison for that endpoint. It therefore does not support a conclusion about how frequently the solicited events occurred in each group, how groups differed, or how precisely any difference was estimated. The fact that the primary outcome was not reduced to one comparison is especially relevant: a reader should not treat an unspecified collection of categories or time points as one reported result.

Serious-event and death counts are available by group, but they remain descriptive. They do not establish causation, and the record does not provide a statistical comparison. The listed serious-event percentages are not assigned to a study group in the information, so they cannot be interpreted as group-specific rates.

The secondary outcomes address immunogenicity and responses to DTaP-IPV, which are separate from injection-site safety. Their outcome definitions are listed, but their results are not reported in the registry record. No conclusion about immune response or comparative immunogenicity follows from the endpoint definitions alone.

The record also does not report the detailed statistical plan, missing-data handling, multiplicity procedures, or uncertainty estimates for the primary endpoint. These limits do not erase the design information or the recorded safety counts; they restrict how far those details can be interpreted. The most defensible reading is that the registry describes the study and some safety observations but does not report enough primary outcome information to assess comparative injection-site event rates.

13. Why This Trial Matters Statistically

This trial raises several useful statistical issues in a compact clinical setting. It has a defined primary safety endpoint, multiple vaccine groups, a repeated vaccination schedule, and secondary outcomes that include both threshold-based immune responses and concentration summaries. Each feature affects how results should be organized and interpreted.

The endpoint is a participant-level percentage, while the assessment period follows each vaccination. When an outcome can be assessed at multiple time points, the choice of summary matters: an analysis may describe each assessment separately or apply another prespecified rule. The registry record notes several categories or time points but does not reduce the primary outcome to one comparison. Without reported estimates and denominators, readers cannot assess the endpoint’s frequency or precision across groups.

The trial also illustrates why safety counts need context. Serious events and deaths are important to report, but descriptive counts do not establish comparative risk or causation. Their interpretation depends on denominators, follow-up, event definitions, and a suitable analysis. The record lists counts at risk and affected, but does not report a statistical comparison for these outcomes.

Finally, the registry lists 6 outcome measures and 135 analyses. That underscores the importance of distinguishing a prespecified primary question from secondary assessments and of describing any approach to multiplicity. The registry record does not report those methodological details. For biostatisticians and clinical researchers, the central lesson is that a clear endpoint definition and trial design are necessary, but they are not substitutes for complete reporting of estimates, uncertainty, analysis populations, and missing-data procedures.

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 main limitation for interpreting this trial is that the primary endpoint’s outcome percentages and comparison are not reported in the registry record. The record states that the primary outcome has several categories or time points and was not reduced to one comparison. As a result, the frequency of solicited injection-site events cannot be described by arm from the recorded information, and no estimate of comparative precision is available.

Although serious adverse-event counts and deaths are listed by group, the registry record does not report statistical comparisons or causal attribution. The term-specific serious-event percentages are not assigned to a group in the information. The counts should therefore be read as descriptive rather than comparative.

The endpoint population is defined as randomized participants who received at least one dose. The record does not report the number analyzed in each arm, the extent of missing outcome data, how missing assessments were handled, or reasons participants may not have contributed data. Those details are needed to evaluate the denominators and potential effects of incomplete follow-up.

The record does not report a detailed statistical analysis plan, a multiplicity strategy, interim analyses, or a sample-size justification. It lists many analyses, but the prespecification and relationship among them are not described. The arm descriptions for V114-SC and PCV13-SC are truncated, limiting the available detail about concomitant vaccination in those groups. Together, these reporting gaps constrain assessment of the primary safety question and the broader secondary outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-028) — NCT03848065.
• Registry record last updated 2025-01-15; status last verified 2025-01.
• Results first posted 2023-10-11.
• 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

This completed Phase I, randomized, multicenter, parallel-group trial evaluated V114 in healthy Japanese infants. The registry record classifies masking as triple, while the official title describes the study as double-blind. The groups were V114-SC, V114-IM, and PCV13-SC, with DTaP-IPV included as a concomitant study vaccine.

The primary endpoint was the percentage of participants with solicited injection-site adverse events from Day 1 to Day 14 after each vaccination. The registry record does not report the primary endpoint percentages or a single comparison. It lists serious adverse-event counts of 1, 3, and 2 by group and deaths of 0, 1, and 0, respectively, without a reported statistical comparison or causal attribution.

Secondary outcomes concerned pneumococcal serotype-specific IgG and protective responses to DTaP-IPV. Their results, along with details of missing-data handling and multiplicity procedures, are not reported in the registry record.