This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-033) (NCT04384107), a randomized phase 3 study. The primary outcome is Percentage of Participants With Solicited Injection-Site Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04384107 |
| Phase | Phase 3 |
| Condition | Pneumococcal Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 694 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Healthy Japanese infants with pneumococcal infections listed as the condition of interest. The registry reports enrollment of 694 participants and defines the primary analysis population as randomized participants who received at least 1 dose of study vaccination.
Intervention
V114, given as a 4-dose schedule: a 3-dose primary series followed by a toddler dose. The first dose was administered at 2 to 6 months of age, the second and third at intervals of ≥27 days from the prior dose, and the fourth at 12 to 15 months of age.
Comparator
Pneumococcal 13-valent Conjugate Vaccine (PCV13), administered on the same stated schedule as V114.
Primary question
The registry’s primary outcome asks what percentage of participants experienced solicited injection-site adverse events after any vaccination, from Day 1 to Day 14 post any vaccination, up to a total of 13.5 months. Separately, the study summary describes non-inferiority hypotheses for immune responses after dose 3. Those hypotheses concern response rates for shared and unique serotypes and IgG geometric mean concentrations for shared serotypes.
The record therefore describes both safety and immunogenicity questions, but the designated primary outcome is an injection-site safety measure. The immunogenicity questions are stated in the study summary; their detailed results are not reported in the registry record. The listed secondary outcomes include antibody concentrations and opsonophagocytic activity after dose 3 or dose 4. These outcomes describe different aspects of immune response and should not be treated as interchangeable with the primary safety endpoint.
3. Trial Design
This was a phase 3, multicenter, randomized, double-blind, active-comparator-controlled study of V114 and PCV13 in healthy Japanese infants. The registry lists a parallel-group model and triple masking. Enrollment was 694. The study is marked completed. The recorded start was 2020-07-01, and primary completion was 2021-12-01.
Participants were assigned to receive V114 or PCV13. Both arms followed the same stated four-dose schedule, with the first dose given at 2 to 6 months of age, the second and third doses at intervals of ≥27 days from the preceding dose, and the fourth dose at 12 to 15 months of age. Each dose is described as a single 0.5 mL subcutaneous injection. Using an active comparator means the study compared one vaccine with another rather than with no vaccination.
The study summary states three non-inferiority hypotheses for immune responses measured 30 days following dose 3: response rates for the 13 shared serotypes, response rates for the 2 unique V114 serotypes, and serotype-specific IgG geometric mean concentrations for the 13 shared serotypes. The registry also lists secondary outcomes measuring IgG concentrations, the percentage meeting a stated IgG threshold after dose 4, and opsonophagocytic activity after dose 3 or dose 4.
The primary outcome, however, is the percentage of participants with solicited injection-site adverse events. It includes erythema, induration, pain, and swelling after any injection. The record does not report the randomization procedure, allocation concealment details, the operational definitions of masking, or the analysis plan for the immunogenicity hypotheses. The reason for the planned enrollment is 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: 694 infants were randomized in a 1:1 ratio with stratification into 3 categories by age category (2 months, 3 months and 4 to 6 months of age), to receive either V114 or Pneumococcal 13-valent Conjugate Vaccine (PCV13).
Overall Study
| Stage | V114 | PCV13 |
|---|---|---|
| STARTED | 347 | 347 |
| Dose 1 | 347 | 346 |
| Dose 2 | 344 | 346 |
| Dose 3 | 343 | 346 |
| Dose 4 | 340 | 342 |
| COMPLETED | 338 | 341 |
| NOT COMPLETED | 9 | 6 |
Reasons for not completing this period:
| Reason | V114 | PCV13 |
|---|---|---|
| Withdrawal By Parent/Guardian | 8 | 6 |
| Lost to Follow-up | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All randomized participants who received at least 1 dose of study vaccination 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.
| Characteristic | Unit | V114 | PCV13 | Total |
|---|---|---|---|---|
| Participants analysed | 347 | 347 | 694 | |
| Age, Continuous | months | 2.4 (SD 0.4) | 2.4 (SD 0.4) | 2.4 (SD 0.4) |
| Age, Customized: Preterm newborn infants (gestational age < 37 wks) | Participants | 0 | 0 | 0 |
| Age, Customized: Newborns (0-27 days) | Participants | 0 | 0 | 0 |
| Age, Customized: Infants and toddlers (28 days-23 months) | Participants | 347 | 347 | 694 |
| Age, Customized: Children (2-11 years) | Participants | 0 | 0 | 0 |
| Age, Customized: Adolescents (12-17 years) | Participants | 0 | 0 | 0 |
| Age, Customized: Adults (18-64 years) | Participants | 0 | 0 | 0 |
| Age, Customized: From 65-84 years | Participants | 0 | 0 | 0 |
| Age, Customized: 85 years and over | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 166 | 173 | 339 |
| Sex: Female, Male: Male | Participants | 181 | 174 | 355 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 347 | 347 | 694 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 347 | 347 | 694 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Solicited Injection-Site Adverse Events, measured over Day 1 to Day 14 post any vaccination, up to a total of 13.5 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with solicited injection-site adverse events after any vaccination. The listed events are erythema, induration, pain, and swelling. The observation window is Day 1 to Day 14 post any vaccination, up to a total of 13.5 months. The primary analysis population is randomized participants who received at least 1 dose of study vaccination.
A percentage expresses how often an event was recorded among the participants considered in the analysis. For this endpoint, it gives a compact description of the frequency of specified local reactions during the stated observation period. The endpoint is relevant to a safety assessment because it focuses on events at the injection site and gathers those events across vaccinations, rather than describing immune response.
The study summary’s immune-response hypotheses are distinct from this primary endpoint. They concern response rates and antibody measurements after dose 3, while the primary endpoint concerns injection-site events after any vaccination. The registry record does not report arm-specific results for the primary endpoint, an effect estimate comparing the arms, or a confidence interval. It is therefore not possible from the registry record to describe the observed between-arm difference or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison of V114 with PCV13 and specifies an injection-site adverse-event percentage as the primary outcome. It does not report the outcome values for either arm or a direct comparison. As a result, no conclusion about the observed frequency of solicited injection-site events, the size or direction of a between-arm difference, or the precision of that difference can be drawn from the recorded primary outcome information.
The study summary also describes non-inferiority hypotheses for immune responses after dose 3. A non-inferiority question asks whether the evidence is compatible with the new intervention being no worse than the comparator by more than a prespecified margin. The margin, the analysis results, and the decision criteria are not reported in the registry record. The existence of a stated hypothesis is not itself evidence that the hypothesis was met. The listed secondary outcomes indicate that immune measures were part of the study, but outcome titles alone do not establish what the results were.
The safety entries list 24 participants with serious adverse events among 347 at risk in the V114 group and 23 among 346 at risk in the PCV13 group. The record also lists 340 participants with other adverse events among 347 at risk in the V114 group and 340 among 346 at risk in the PCV13 group. These are counts, not adjusted comparisons, and the registry record does not provide confidence intervals or a statistical test for these group contrasts. The recorded death counts are 0 in each group. The serious-event terms and their listed percentages provide additional descriptive detail, but they do not replace the overall arm-level outcome information.
Interpretation also depends on knowing how outcomes were collected, how missing observations were handled, and which participants contributed to each analysis. The primary population is described, but outcome-specific denominators and missing-data methods are not reported in the registry record. The record lists 10 outcome measures and 98 analyses, but does not describe how multiplicity was addressed. Multiple analyses can make it harder to distinguish prespecified confirmatory findings from exploratory results unless the analysis plan and decision rules are known.
Sample-size calculations in a planning illustration are not observed trial findings and do not establish the study’s actual design rationale. The stated assumptions for that illustration include a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. The record does not report the trial’s own sample-size justification. In particular, those planning assumptions should not be mistaken for a reported power analysis or for evidence that any clinical or immunogenicity objective was achieved.
9. Statistical Methods Explained
What does a percentage measure?
General: A percentage is the share of participants in a defined analysis group who experienced an event during a defined period. It is useful for describing binary outcomes, such as whether a participant had at least one solicited injection-site adverse event. Interpretation requires both the event definition and the population counted in the denominator. The registry defines the primary population as randomized participants who received at least 1 dose, and it specifies an observation period after any vaccination.
The primary endpoint is a participant-level percentage, not a measure of the number of separate reactions per participant or their severity. The listed local events are erythema, induration, pain, and swelling. The description does not state how repeated events were counted or how severity categories were handled, and those details are not reported in the registry record.
What does randomization contribute?
General: Random assignment is intended to make treatment groups comparable, on average, with respect to measured and unmeasured characteristics at the start of a trial. It does not guarantee identical groups in every realized study. The registry describes the study as randomized, double-blind, and parallel-group, and identifies PCV13 as the active comparator. The specific randomization method and details of how assignment was concealed are not reported in the registry record.
Masking is intended to limit the influence of knowledge about assigned treatment on participant experience, clinical care, or outcome assessment. The registry lists triple masking but does not identify which people or roles were masked, or describe how masking was maintained. The label therefore describes the recorded design but does not provide enough detail to evaluate implementation.
How should the non-inferiority hypotheses be understood?
General: A non-inferiority analysis evaluates whether an intervention’s result is not unacceptably worse than a comparator, according to a margin chosen before interpreting the data. The margin is central: it defines how much difference would still count as non-inferior. A confidence interval is an interval estimate that conveys uncertainty around an estimated effect; in a non-inferiority assessment, its position relative to the margin matters. Neither the non-inferiority margin nor the immune-response estimates and confidence intervals are reported in the registry record.
The study summary names hypotheses involving response rates for the shared serotypes, response rates for the unique V114 serotypes, and IgG geometric mean concentrations for the shared serotypes, all after dose 3. The outcomes listed separately include geometric mean concentrations for the unique serotypes and several measures after dose 4. The registry record does not provide the statistical procedures, decision rules, or results for these analyses. It is not possible to infer a non-inferiority finding from a hypothesis statement or an outcome title.
What does a geometric mean represent?
General: A geometric mean is commonly used for measurements that are positive and have a right-skewed distribution, such as antibody concentrations or titers. It is calculated on a logarithmic scale and then expressed on the original scale. It describes a central level, but by itself does not show the spread of individual responses or the proportion of participants above a threshold. The registry lists IgG geometric mean concentrations and opsonophagocytic activity geometric mean titers as outcomes; their values and analysis details are not reported in the registry record.
Why do dispersion and over-dispersion matter?
General: An estimate of a central value is more informative when accompanied by a measure of variability or an interval estimate. If participant outcomes vary more than a chosen statistical model expects, the data may be over-dispersed relative to that model. Ignoring over-dispersion can make uncertainty appear smaller than it is. The registry record does not report dispersion estimates or model diagnostics for the trial outcomes, so this issue cannot be evaluated for the posted analyses.
What is the role of a planning illustration?
General: A sample-size calculation describes the amount of information that a design might need under specified assumptions. It depends on choices such as the target effect, variability, significance level, allocation, and analysis method. A planning calculation based on an observed effect is an illustration, not proof that the original trial had a particular power and not a substitute for the trial’s design justification.
The stated illustration uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect expressed as a fraction of the observed effect. The registry record does not report the trial’s own sample-size justification or its full design assumptions. It also does not report a primary endpoint comparison from which to assess the observed effect in the registry record. No planning illustration should be read as observed power or as a result of the trial.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 10 outcome measures and 98 analyses, alongside several immune-response hypotheses and a primary safety endpoint. When many endpoints, time points, or analyses are examined, the chance of a nominally notable result arising by chance can increase. Statistical approaches to multiplicity may control that risk or define a hierarchy of confirmatory questions. Which approach was used, whether a testing hierarchy was prespecified, and which analyses were considered confirmatory are not reported in the registry record.
The registry identifies the primary analysis population as all randomized participants who received at least 1 dose of study vaccination. It does not describe the analysis populations used for the immune-response outcomes or the safety entries. Outcome-specific participant counts, exclusions, and reasons for missing measurements are not reported in the registry record.
Missing-data handling can affect an estimate when participants without a recorded outcome differ systematically from those with observed outcomes. General: An analysis may use complete observations, imputation, or other assumptions about missing values; each approach relies on assumptions that should be stated and assessed. The registry record does not report the missing-data strategy, sensitivity analyses, or how incomplete follow-up was treated.
The record does not report a statistical analysis plan, the prespecified hypothesis-testing procedure, or whether any interim analyses were planned or conducted. These omissions limit assessment of how the many listed analyses relate to the stated study questions and how robust any reported results would be. Because arm-level primary outcome results are also not reported, no multiplicity-adjusted primary comparison can be interpreted from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| V114 | 24 | 347 | 6.9% |
| PCV13 | 23 | 346 | 6.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| V114 | 0 of 347 |
| PCV13 | 0 of 347 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| V114 | 340 of 347 |
| PCV13 | 340 of 346 |
Most frequent serious adverse event terms
| Event term | Organ system | V114 | PCV13 |
|---|---|---|---|
| Respiratory syncytial virus infection | Infections and infestations | 4 of 347 | 3 of 346 |
| Urinary tract infection | Infections and infestations | 4 of 347 | 1 of 346 |
| Food allergy | Immune system disorders | 3 of 347 | 1 of 346 |
| Pneumonia | Infections and infestations | 3 of 347 | 1 of 346 |
| Bacterial infection | Infections and infestations | 1 of 347 | 2 of 346 |
| Bronchitis | Infections and infestations | 1 of 347 | 2 of 346 |
| Respiratory syncytial virus bronchitis | Infections and infestations | 1 of 347 | 2 of 346 |
| Kawasaki's disease | Vascular disorders | 1 of 347 | 2 of 346 |
| Milk allergy | Immune system disorders | 1 of 347 | 1 of 346 |
| Gastroenteritis norovirus | Infections and infestations | 1 of 347 | 1 of 346 |
Most frequent non-serious adverse event terms
| Event term | Organ system | V114 | PCV13 |
|---|---|---|---|
| Injection site erythema | General disorders | 306 of 347 | 309 of 346 |
| Injection site induration | General disorders | 281 of 347 | 281 of 346 |
| Injection site swelling | General disorders | 263 of 347 | 276 of 346 |
| Pyrexia | General disorders | 227 of 347 | 252 of 346 |
| Irritability | Psychiatric disorders | 231 of 347 | 210 of 346 |
| Somnolence | Nervous system disorders | 194 of 347 | 190 of 346 |
| Injection site pain | General disorders | 108 of 347 | 83 of 346 |
| Decreased appetite | Metabolism and nutrition disorders | 83 of 347 | 84 of 346 |
| Nasopharyngitis | Infections and infestations | 32 of 347 | 37 of 346 |
| Erythema | Skin and subcutaneous tissue disorders | 33 of 347 | 31 of 346 |
Serious events with the highest arm-level rate: respiratory syncytial virus infection (1.2%), urinary tract infection (1.2%), food allergy (0.9%), pneumonia (0.9%), bacterial infection (0.6%).
The safety entries list serious adverse events in both groups: 24 participants among 347 at risk for V114 and 23 among 346 at risk for PCV13. Other adverse events are listed for 340 participants among 347 at risk in the V114 group and 340 among 346 at risk in the PCV13 group. The recorded death count is 0 in each group. These entries are descriptive counts; the registry record does not report a statistical comparison, confidence interval, or adjustment for differences between groups.
The most frequent serious adverse-event terms listed are Respiratory syncytial virus infection and Urinary tract infection, each at 1.2%; Food allergy and Pneumonia, each at 0.9%; and Bacterial infection and Bronchitis, each at 0.6%. These percentages describe the registry’s listed terms, not the overall primary endpoint of solicited injection-site events. The record does not provide further details about event onset, duration, severity, relatedness, recurrence, or participant overlap among terms. Counts and listed percentages alone cannot establish whether events were caused by a study vaccine or support a causal comparison. The primary endpoint results are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record establishes that a randomized, double-blind, active-comparator-controlled phase 3 study evaluated a four-dose V114 schedule against PCV13 in healthy Japanese infants. It specifies a primary safety outcome based on solicited injection-site events and describes non-inferiority hypotheses concerning immune responses after dose 3. It also records safety counts and selected serious adverse-event terms.
Those design details do not establish the study’s findings. The primary endpoint’s arm-specific percentages and comparative estimate are not reported in the registry record. The immune-response results, non-inferiority margin, confidence intervals, and statistical decision criteria are also not reported. Consequently, the stated hypotheses cannot be treated as conclusions, and the registry record does not establish whether either vaccine had a higher or lower observed injection-site event percentage.
The serious adverse-event entries are useful as descriptive information about recorded events and at-risk participants. They are not, by themselves, evidence of a causal effect or a formal comparison between groups. The absence of recorded deaths in the listed entries should be read as a count in this record, not as a general statement about risk outside the study or beyond its reported follow-up.
More broadly, a trial result is interpreted in light of its population, outcome definitions, analysis methods, missing observations, and uncertainty. The registry record describes some of these elements but does not report several essential details, including the statistical analysis plan, multiplicity handling, and outcome-specific missing-data methods. The available information therefore supports a description of the study design and recorded safety entries, but not a conclusion about comparative efficacy, non-inferiority, or the size and precision of the primary safety effect.
13. Why This Trial Matters Statistically
This trial is statistically notable for placing a safety endpoint and several immunogenicity questions within the same study record. The designated primary outcome measures solicited injection-site events, while the study summary describes non-inferiority hypotheses based on immune responses after dose 3. Keeping these questions distinct matters: an event percentage and an antibody response measure different outcomes and require different interpretations.
The active-comparator design also shapes the scientific question. The comparison is between V114 and PCV13, with the same stated dose schedule in both arms. For the immune-response hypotheses, a non-inferiority conclusion would depend on the prespecified margin and the relevant estimate and uncertainty. Those details and results are not reported in the registry record, so the hypothesis statements cannot be evaluated from the available information.
The registry’s safety entries illustrate why denominators and outcome definitions matter. Counts are presented alongside the number at risk, while the primary endpoint description specifies a set of solicited injection-site events and a particular follow-up window. The serious-event entries are a separate descriptive safety presentation and cannot be substituted for the primary endpoint comparison.
Finally, the record lists many analyses but does not report the analysis plan, multiplicity handling, or missing-data methods. These omissions constrain reproducibility and make it difficult to distinguish confirmatory analyses from additional outcome assessments. The trial’s design can be described, but a statistical assessment of its principal comparative findings requires outcome estimates, uncertainty measures, and analysis details that are not reported in the registry record.
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 most consequential limitation for interpreting the trial from the registry record is the absence of reported results for the designated primary endpoint. No arm-specific percentage, comparative effect estimate, or confidence interval for solicited injection-site events is reported. The immune-response estimates and results of the stated non-inferiority hypotheses are also not reported.
The registry record does not report the non-inferiority margin or the statistical analysis plan. It does not specify the procedures used to account for the 10 outcome measures and 98 analyses, or whether any hierarchy or multiplicity adjustment was applied. The analysis populations and denominators for the immunogenicity outcomes are not described, and missing-data methods are not reported.
Some design details are also absent: the randomization procedure, allocation concealment, the roles covered by triple masking, and the trial’s sample-size justification are not reported in the registry record. The listed planning assumptions are not a substitute for that justification. The record does not report interim-analysis plans or whether interim analyses occurred.
For safety, the record gives group-level serious and other adverse-event counts, a death count, and selected serious-event terms. It does not provide detailed event timing, severity, relatedness, participant overlap, or a formal between-group analysis. These omissions mean the safety entries are descriptive rather than a complete statistical comparison. More generally, registry information alone does not provide all the detail needed to assess outcome ascertainment, analysis robustness, or the clinical interpretation of differences.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-033) — NCT04384107.
- Registry record last updated 2023-07-28; status last verified 2023-07.
- Results first posted 2022-11-15.
- 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.
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18. Record Summary
NCT04384107 is a completed phase 3, randomized, parallel-group, triple-masked study comparing V114 with PCV13 in healthy Japanese infants. Enrollment was 694. Both groups followed the stated four-dose schedule, beginning at 2 to 6 months of age and ending with a dose at 12 to 15 months.
The primary outcome is the percentage of participants with solicited injection-site adverse events after any vaccination, assessed from Day 1 to Day 14 post any vaccination, up to a total of 13.5 months. The study summary also states non-inferiority hypotheses for immune responses after dose 3. Primary endpoint and immunogenicity results are not reported in the registry record.
Safety entries list serious adverse events in 24 participants in the V114 group and 23 in the PCV13 group, with 0 deaths recorded in each group. Statistical analysis details, multiplicity handling, and missing-data methods are not reported in the registry record.