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 Safety, Tolerability, and Immunogenicity of Vaxelis™ in Children Previously Vaccinated With Vaxelis™ or Hexyon™ (V419-016) (NCT05289271), a non-randomized phase 4 study. The primary outcome is Percentage of Participants With a Solicited Injection-site Adverse Event (AE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05289271 |
| Phase | Phase 4 |
| Condition | Vaccines, Combined, Hexavalent Vaccine |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 168 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Healthy children previously vaccinated with a 2-dose primary infant series of either Vaxelis™ or Hexyon™. The study objective describes a booster at ~11 to 13 months of age.
Intervention
A booster dose of Vaxelis™. The registry record describes the study as open-label and identifies Vaxelis™ as the study intervention.
Comparator
There is no randomized control group. The two groups differ by their prior infant vaccine: one received Vaxelis™ and the other Hexyon™; both received a Vaxelis™ booster.
Primary question
What percentage of vaccinated participants had a solicited injection-site adverse event through 5 days postvaccination? The registry record does not report the result for this primary endpoint.
The study also aimed to evaluate safety, tolerability, and immunogenicity after the booster. The listed secondary outcomes include pertactin and fimbriae 2/3 vaccine responses, but their results are not reported in the registry record. The design therefore frames two descriptive questions: what was observed after the booster in each prior-vaccination group, and how do the reported safety observations differ across those groups? Because allocation was non-randomized and both groups received the same booster, the groups do not form a like-for-like randomized comparison. Differences in observed outcomes cannot be attributed to prior vaccine history alone on the basis of this design. The posted information is useful for understanding the endpoint definitions, follow-up window, group structure, and recorded safety counts, but it does not establish a comparative effect or provide the primary endpoint estimates.
3. Trial Design
This was a Phase 4, open-label, multicenter, parallel study with non-randomized allocation. It enrolled 168 participants and is listed as completed. The registry record gives a start date of 2022-03-25 and a primary completion date of 2022-08-30. Participants were healthy children who had previously received a 2-dose primary infant series of Vaxelis™ or Hexyon™.
The study had two groups. Group 1, described as V, V, V, comprised participants who had received a 2-dose Vaxelis™ regimen as infants and then received a Vaxelis™ booster at ~11 months of age. Group 2, described as H, H, V, comprised participants who had received a 2-dose Hexyon™ regimen as infants and then received a Vaxelis™ booster at ~11 months of age. Both groups therefore received Vaxelis™ as the booster. The difference between the groups is the previously received primary series, not the booster intervention.
Open-label means that the study was not masked. Non-randomized means that participants were not assigned to the two groups by random allocation. The registry record does not describe how participants entered each group, so the basis for group membership beyond prior vaccination is not reported in the registry record. These design features matter when interpreting differences between groups: the record specifically cautions that the arms are not a like-for-like control comparison.
The stated primary objectives were to evaluate safety, tolerability, and immunogenicity of the booster. The primary listed outcome was the percentage of participants with a solicited injection-site adverse event through 5 days postvaccination. The population named for that outcome is all participants who received study vaccination. The registry record lists 15 outcome measures and 0 analyses. Details of the statistical analysis plan, including any prespecified group comparisons, are 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.
Overall Study
| Stage | Group 1: V, V, V | Group 2: H, H, V |
|---|---|---|
| STARTED | 86 | 82 |
| Treated | 85 | 82 |
| COMPLETED | 85 | 82 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Group 1: V, V, V | Group 2: H, H, V |
|---|---|---|
| Mistakenly allocated, untreated | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants who received study 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.
| Characteristic | Unit | Group 1: V, V, V | Group 2: H, H, V | Total |
|---|---|---|---|---|
| Participants analysed | 86 | 82 | 168 | |
| Age, Continuous | Days | 348.8 (SD 18.8) | 344.7 (SD 16.4) | 346.8 (SD 17.7) |
| Sex: Female, Male: Female | Participants | 44 | 33 | 77 |
| Sex: Female, Male: Male | Participants | 42 | 49 | 91 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 45 | 60 | 105 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 34 | 21 | 55 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 7 | 1 | 8 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 |
| 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 | 85 | 82 | 167 |
| 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 a Solicited Injection-site Adverse Event (AE), measured over Up to 5 days postvaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with a solicited injection-site adverse event through 5 days postvaccination. The events are predefined local events at the injection or administration site: swelling, redness (erythema), and pain or tenderness. A participant’s legally authorized representative was specifically questioned about these events and used a Vaccination Report Card to report them. The stated analysis population is all participants who received study vaccination.
This endpoint expresses the number of participants with at least one qualifying event as a percentage of the participants in the relevant population. It is a binary outcome at the participant level: a participant either met the event definition or did not. The endpoint description does not specify how multiple event types or repeated reports for one participant were combined, beyond defining the outcome as the percentage of participants with a solicited injection-site adverse event; further rules are not reported in the registry record.
General statistical context: solicited outcomes are collected by asking about specifically defined events rather than relying only on spontaneous reporting. A defined follow-up window helps delimit the period to which the percentage applies. It does not describe events outside that window, and the percentage is not a measure of event severity. The record says that 95% confidence intervals were calculated using the exact binomial method proposed by Clopper and Pearson. However, the primary endpoint estimate and its interval are not reported in the registry record, so the frequency and precision of the outcome cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the primary endpoint and method but does not report the endpoint’s percentage or confidence interval. It is therefore not possible to state how many participants had a solicited injection-site adverse event, or how precisely that percentage was estimated. The primary outcome results are not reported in the registry record. The record also lists 0 analyses, so it does not provide a reported statistical comparison for this outcome.
The safety figures that are present are counts of participants with serious adverse events and other adverse events in each group. In Group 1, 85 participants were at risk for serious adverse events, 0 were recorded with a serious adverse event, 85 were at risk for other adverse events, and 83 were recorded with other adverse events. In Group 2, the corresponding figures are 82 at risk for serious adverse events, 1 with a serious adverse event, 82 at risk for other adverse events, and 75 with other adverse events. Deaths are recorded as 0 in both groups. The registry lists “Gastroenteritis adenovirus” as a top serious adverse event term at 1.2%; it does not identify the group for that term in the posted information.
These counts are descriptive. The study did not randomize participants to prior-vaccine groups, and both groups received the Vaxelis™ booster. The registry record cautions that the arms are not a like-for-like control comparison. Thus, the counts do not establish that one prior-vaccination history caused a difference in adverse events, and they should not be read as a randomized estimate of comparative risk.
The stated secondary outcomes include pertactin and fimbriae 2/3 vaccine responses, but outcome results are not reported in the registry record. The record’s aim includes immunogenicity, yet the posted information does not permit an interpretation of vaccine-response frequencies, their precision, or differences between groups. No estimate should be inferred from the study objectives or from the existence of listed outcomes.
For statistical interpretation, the key distinction is between a study objective and a reported result. The objectives explain what the trial was intended to evaluate. The group counts show some recorded safety information. Neither substitutes for the missing primary endpoint estimate, confidence interval, or analysis results. As a result, the registry supports a description of the design and selected safety counts, but not a complete quantitative assessment of the stated objectives.
9. Statistical Methods Explained
The primary outcome is a percentage, with each vaccinated participant classified according to whether a solicited injection-site adverse event was reported during the specified follow-up window. The event definition includes swelling, redness (erythema), and pain or tenderness at the injection or administration site. The participant’s legally authorized representative was specifically asked about these predefined events and used a Vaccination Report Card to report them. The endpoint population is all participants who received study vaccination. The registry record does not report the primary estimate or the number of participants meeting this endpoint.
What does a confidence interval describe?
General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity. For a percentage, its width depends in part on the amount of information available and on how common the event is. A narrower interval indicates greater statistical precision for the estimate; a wider interval indicates less precision. A confidence interval does not show that the estimate is free of bias, and it does not account automatically for limitations such as non-random group formation or incomplete outcome reporting.
The endpoint description states that 95% confidence intervals were calculated using the exact binomial method proposed by Clopper and Pearson. General statistical explanation: this method constructs an interval for a binomial proportion, such as the percentage of participants with an event. It is termed exact because it uses the binomial distribution rather than relying on a normal approximation for that interval. This method is relevant to a binary participant-level outcome, especially when event counts may be small. No confidence limits for the primary outcome are reported in the registry record, so the method alone does not reveal the estimated percentage or its precision.
What does the design permit?
The study is open-label, parallel, and non-randomized. Group membership reflects the previously received primary series: Vaxelis™ in Group 1 and Hexyon™ in Group 2. Both groups received a Vaxelis™ booster. General statistical explanation: random allocation helps balance measured and unmeasured participant characteristics across treatment groups on average. Without random allocation, group differences may reflect factors associated with group membership as well as any effect related to the prior vaccine. The record does not describe adjusted analyses that might address measured differences, and it reports 0 analyses. The registry record explicitly cautions that the groups are not a like-for-like control comparison.
The study’s parallel structure means that outcomes are described across separate groups rather than as repeated treatment periods for the same participants. The record does not report a randomized assignment procedure or masking. Since the study was open-label, participants and study personnel were not masked according to the registry description. General statistical explanation: awareness of group or treatment can influence reporting or assessment for outcomes that rely on observation or participant reporting. The use of predefined local events and a Vaccination Report Card specifies how the solicited endpoint was collected, but does not remove all possible reporting effects.
How should the planning illustrations be understood?
The stated planning illustrations are based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the stated sample-size convention is participants per arm; time-to-event illustrations would use total events, but the primary endpoint is a percentage. The registry record does not report the numerical planning outputs in the registry record for this analysis.
General statistical explanation: a sample-size calculation is conditional on its assumptions about the effect to detect, variability, allocation, and statistical error rate. An illustration built from an observed effect is a planning exercise, not evidence that the study had a particular probability of detecting an effect. It is not observed power. The trial’s own sample-size justification and design assumptions are not reported in the registry record. No inference about the adequacy of enrollment for the primary or secondary endpoints can be made from the enrollment count alone.
Finally, analysis choices affect how percentages and comparisons are interpreted. The endpoint population is described as participants who received study vaccination, but the registry record does not explain the handling of missing reports, withdrawals, or participants with incomplete follow-up. It also does not report a statistical analysis plan, any adjustment for covariates, or inferential results for group comparisons. These omissions limit assessment of the exact analysis population and the robustness of any potential estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome and secondary outcomes, including the percentage of participants with a pertactin vaccine response and the percentage with a fimbriae 2/3 vaccine response. It lists 15 outcome measures overall and 0 analyses. The posted record does not provide results for those vaccine-response outcomes or state how multiple outcomes were handled statistically.
General statistical explanation: when a study evaluates multiple outcomes or makes multiple statistical comparisons, the chance of at least one apparently unusual result can increase if each is assessed separately. A prespecified multiplicity strategy can control or describe this issue. Whether such a strategy was planned for this study is not reported in the registry record. There are no reported analysis results from which to assess whether an adjustment was applied.
The primary endpoint identifies the population as all participants who received study vaccination. The registry record does not specify how missing Vaccination Report Card entries, incomplete follow-up, or other missing outcome data were handled. It does not report whether participants with incomplete records were excluded, counted as having no event, or treated through another approach. Those details are not reported in the registry record, so the completeness of the primary endpoint data cannot be assessed.
The record also does not describe analysis populations for the listed immunogenicity outcomes or explain whether those populations differed from the safety population. It is therefore not possible to determine which participants contributed to any unreported vaccine-response analyses. The absence of an analysis description does not show that a particular method was or was not used; it means that the approach is not reported in the registry record. Consequently, the posted information supports only limited descriptive interpretation and does not allow evaluation of multiplicity control or missing-data sensitivity.
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 |
|---|---|---|---|
| Group 1: V, V, V | 0 | 85 | 0.0% |
| Group 2: H, H, V | 1 | 82 | 1.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1: V, V, V | 0 of 86 |
| Group 2: H, H, V | 0 of 82 |
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 |
|---|---|
| Group 1: V, V, V | 83 of 85 |
| Group 2: H, H, V | 75 of 82 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1: V, V, V | Group 2: H, H, V |
|---|---|---|---|
| Gastroenteritis adenovirus | Infections and infestations | 0 of 85 | 1 of 82 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1: V, V, V | Group 2: H, H, V |
|---|---|---|---|
| Irritability | Psychiatric disorders | 66 of 85 | 48 of 82 |
| Injection site pain | General disorders | 63 of 85 | 46 of 82 |
| Somnolence | Nervous system disorders | 55 of 85 | 39 of 82 |
| Injection site erythema | General disorders | 45 of 85 | 41 of 82 |
| Injection site swelling | General disorders | 45 of 85 | 33 of 82 |
| Pyrexia | General disorders | 34 of 85 | 40 of 82 |
| Decreased appetite | Metabolism and nutrition disorders | 37 of 85 | 30 of 82 |
| Vomiting | Gastrointestinal disorders | 5 of 85 | 8 of 82 |
| Diarrhoea | Gastrointestinal disorders | 1 of 85 | 6 of 82 |
| Injection site induration | General disorders | 0 of 85 | 6 of 82 |
Serious events with the highest arm-level rate: gastroenteritis adenovirus (1.2%).
The registry record reports serious and other adverse event counts by group, alongside the participants at risk. In Group 1, 0 of 85 participants at risk were recorded with a serious adverse event, and 83 of 85 were recorded with other adverse events. In Group 2, 1 of 82 participants at risk was recorded with a serious adverse event, and 75 of 82 were recorded with other adverse events. There were 0 deaths in each group. These are the posted counts; they should not be taken as a complete account of the primary solicited injection-site endpoint, whose result is not reported in the registry record.
The listed top serious adverse event term is “Gastroenteritis adenovirus” at 1.2%. The registry record does not state which group this term belongs to in the posted information, nor does it provide further details about the event. The one serious adverse event recorded in Group 2 cannot be linked to that term from the information reported.
General statistical explanation: safety counts describe events observed during the recorded study period and depend on how events were defined, collected, and classified. The registry record does not provide additional detail about the collection window for these serious and other adverse event counts. Also, because the groups were not randomized and are not a like-for-like control comparison, the counts are descriptive rather than evidence of a causal difference between prior-vaccination groups.
12. What the Result Does, and Does Not, Mean
The posted information establishes that this completed Phase 4 study evaluated a Vaxelis™ booster in healthy children previously given a 2-dose primary infant series of either Vaxelis™ or Hexyon™. It specifies the primary safety endpoint, its follow-up window, the event types included, and the stated confidence-interval method. It also reports selected serious and other adverse event counts and deaths by group.
It does not report the primary endpoint percentage or its 95% confidence interval. It does not report results for the listed pertactin and fimbriae 2/3 vaccine-response outcomes. Although the study objectives included safety, tolerability, and immunogenicity, the objectives are not evidence of the outcome results. The registry lists 15 outcome measures but 0 analyses, so the posted information does not give a quantitative analysis of the primary question or the secondary response questions.
The study also does not establish a randomized comparison of the two prior-vaccination histories. Group membership was non-randomized, and both groups received Vaxelis™ as a booster. The registry record cautions that the arms are not a like-for-like control comparison. Any observed difference in the reported safety counts could reflect factors associated with group membership or other features of the study, and cannot be attributed to prior vaccination on the basis of these counts alone.
General statistical explanation: a point estimate describes an observed frequency, while an interval conveys its sampling uncertainty. Neither by itself resolves bias from design or data collection. Here, the missing primary estimate and interval prevent assessment of both the frequency of solicited injection-site events and its precision. The available counts can be described as recorded safety observations, but they cannot establish comparative safety, immunogenicity, or a causal effect. The registry record also does not report details needed to assess missing outcomes, multiplicity, or the full analysis population.
13. Why This Trial Matters Statistically
This study raises a clear statistical distinction between describing outcomes in two cohorts and making a controlled comparison. Each group received the same Vaxelis™ booster, while prior vaccination differed: Vaxelis™ in one group and Hexyon™ in the other. Because allocation was non-randomized, the groups do not constitute a like-for-like control comparison. That design feature is central to interpreting any difference in the recorded outcomes.
The primary endpoint is also specific and time-bounded: the percentage of vaccinated participants with solicited injection-site events through 5 days postvaccination. Defining the events and collection method makes the question more concrete, while the reported Clopper and Pearson method identifies how the confidence interval was intended to be calculated. Yet those methods do not supply the missing estimate or interval. The registry record does not report the primary result, so readers cannot assess the event frequency or its precision.
The record illustrates why objectives, outcome definitions, and results must be distinguished. Safety, tolerability, and immunogenicity are stated aims, and vaccine-response outcomes are listed, but the registry provides no results for them and lists 0 analyses. The safety counts that are posted are informative as descriptions of events recorded in the groups; they do not fill in the missing primary endpoint or immunogenicity analyses.
General statistical explanation: a well-defined estimand and analysis plan help readers connect an outcome, population, and comparison to the reported estimate. The registry record identifies the primary population as participants who received study vaccination, but does not describe missing-data handling, multiplicity, or the full analysis plan. These details matter for understanding exactly what a reported percentage would represent. In this trial, their absence together with the absence of endpoint results limits the statistical conclusions that can be drawn from the public 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 direct limitation for interpretation is that the registry record does not report the primary endpoint result, its confidence interval, or analyses. This prevents assessment of the percentage of participants with solicited injection-site adverse events and the precision of that estimate. The listed vaccine-response outcomes also lack reported results.
The study was open-label and non-randomized. Its groups differed in their prior infant vaccine, but both received a Vaxelis™ booster. The registry explicitly cautions that the arms are not a like-for-like control comparison. This limits causal interpretation of between-group differences and means that the safety counts should be read descriptively.
The registry record describes the primary endpoint population as all participants who received study vaccination, but does not report how missing or incomplete endpoint reports were handled. The full analysis populations for other outcomes are not described. It also does not report the statistical analysis plan, multiplicity approach, adjusted analyses, or the study’s own sample-size justification. These omissions leave uncertainty about analysis choices and the intended basis for statistical inference.
The safety information is limited to the counts reported by group, deaths, and a listed top serious adverse event term. Further detail about the serious event term and its group is not reported in the posted information. The record does not give enough information to characterize event timing or other details for those counts. Finally, although enrollment is listed as 168, that number alone does not establish how many participants contributed data to each outcome. The outcome-specific denominators and results are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, and Immunogenicity of Vaxelis™ in Children Previously Vaccinated With Vaxelis™ or Hexyon™ (V419-016) — NCT05289271.
- Registry record last updated 2024-07-29; status last verified 2024-07.
- Results first posted 2023-09-06.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT05289271 is a completed Phase 4, open-label, multicenter, parallel, non-randomized study of a Vaxelis™ booster in healthy children previously vaccinated with a 2-dose primary infant series of Vaxelis™ or Hexyon™. Enrollment is listed as 168. The study start date is 2022-03-25, and the primary completion date is 2022-08-30.
The primary listed outcome is the percentage of vaccinated participants with a solicited injection-site adverse event through 5 days postvaccination. The registry record describes the event types and states that 95% confidence intervals were calculated using the exact binomial method proposed by Clopper and Pearson. The primary outcome result and its interval are not reported in the registry record. The record lists 15 outcome measures and 0 analyses.
Reported safety counts include serious and other adverse events in each group and 0 deaths in both groups. The record cautions that the non-randomized groups are not a like-for-like control comparison. Results for the listed vaccine-response outcomes are not reported in the registry record.