Safety and Immunogenicity of Pneumococcal Conjugate Formulations in Healthy Adults 18 Through 49 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of Pneumococcal Conjugate Formulations in Healthy Adults 18 Through 49 Years of Age (NCT05489328), a randomized phase 1 study. The primary outcome is Percentage of Participants With Local Reactions Within 7 Days After Administration of Study Intervention.

2. Clinical Question

The study is registered as a phase 1 randomized, open-label, parallel trial in healthy adults, with Pneumococcal Disease listed as the condition. Its stated purpose is to describe the safety and immunogenicity of pneumococcal conjugate formulations. That descriptive purpose is consistent with examining local reactions and immune-response measures across several arms, rather than treating the record as a report of one definitive comparison.

A secondary outcome concerns serotype-specific pneumococcal opsonophagocytic activity, or OPA, geometric mean titers one month after administration, comparing each candidate group with Candidate Control. Numerical OPA results are not reported in the registry record. The record identifies five outcome measures overall, but does not supply result values or analysis details for those measures in the information available.

3. Trial Design

This was a phase 1, randomized, open-label trial with a parallel-group model. The registry lists enrollment of 394 participants and records the study as completed. The start date was 2022-08-15, and the primary completion date was 2022-10-07. The sponsor was Pfizer.

The arm descriptions specify a single injection for each listed group: Candidate-1, Candidate-2, Candidate-3, Candidate-4, Candidate-5, Candidate-6, Candidate Control, 13-valent pneumococcal conjugate vaccine (13vPnC), and 15-valent pneumococcal conjugate vaccine (PCV15). The intervention listings also include Candidate-1 through Candidate-6, Candidate Control, and 13vPnC. The registry does not explain the difference in how the intervention list and arm descriptions identify the products, nor does it provide the randomization ratio or participant counts assigned to each arm.

Randomization is intended to assign participants to study groups by chance, which can help balance measured and unmeasured characteristics across groups. In an open-label design, participants and study personnel are not masked to assigned intervention. This can matter when outcomes involve symptoms reported by participants, since knowledge of assignment may influence how symptoms are noticed or recorded. The registry does not report additional procedures intended to mitigate that possibility.

The primary endpoint measures local reactions within 7 days after intervention. The safety population is defined as all participants who received study intervention. The record also identifies a one-month immune-response outcome based on serotype-specific OPA geometric mean titers. Further details about follow-up beyond the stated endpoint timeframes, allocation procedures, and the planned statistical analysis are not reported in the registry record.

Although the trial is completed, completion status alone does not indicate how complete the posted outcome results are. The registry lists five outcome measures and zero analyses. It does not report a protocol-level sample-size justification, planned interim analyses, or a detailed statistical analysis plan. The sample-size assumptions recorded for a planning illustration are not identified as the trial’s design assumptions.

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: A total of 394 participants were enrolled and randomized in the study of which 3 participants were not vaccinated and, 391 were administered study intervention. One participant randomized to Candidate-Control received Candidate-4.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who received the study intervention.

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.

Population: Analysis was performed on safety population which included all participants who received the study intervention. Participants were summarized according to the study intervention they received.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Local Reactions Within 7 Days After Administration of Study Intervention, measured over Within 7 days after study intervention.

The primary endpoint is the percentage of participants with local reactions within 7 days after administration of study intervention. The listed reactions are redness, swelling, and pain at the injection site. Redness and swelling were measured and recorded in measuring-device units, with one unit equal to 0.5 centimeter. The registry describes severity categories for redness and swelling and separate severity categories for pain. Pain grading is based on interference with activity; the case-report-form severity definition also describes interference with usual function.

Local reactions are useful safety outcomes in a vaccine study because they capture symptoms occurring at the injection site over a defined period after administration. Reporting the percentage of participants affected expresses the event frequency relative to the safety population, rather than only giving an event count. The endpoint’s stated timeframe is within 7 days, and the registry says the safety population includes all participants who received study intervention.

The registry specifies an exact two-sided 95% confidence interval based on the Clopper and Pearson method for this endpoint. A confidence interval conveys uncertainty around an estimated event percentage: it gives a range of values compatible with the observed data under the method’s assumptions. It is not, by itself, a measure of clinical importance, and interval overlap is not a substitute for a prespecified between-group comparison.

The numerical primary-endpoint results are not reported in the registry record in a form that reduces the multiple categories or time points to one comparison. Consequently, the listed safety counts for other adverse-event summaries should not be read as primary local-reaction percentages.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial record identifies randomization, an open-label design, parallel groups, a percentage endpoint, and a confidence-interval method. It does not report a full statistical analysis plan. The following explanations describe the general meaning of the named methods, while distinguishing them from analyses or procedures not documented for this trial.

What does randomization contribute?

In general, random assignment is used to reduce systematic differences between intervention groups at the start of a trial. It does not guarantee that every characteristic will be balanced, especially in a study with several arms and modest group sizes. The registry states that allocation was randomized but does not report the sequence-generation method, concealment procedure, allocation ratio, or stratification factors. Those details therefore cannot be assessed from the registry record.

What does an open-label design imply?

In general, open-label means that intervention assignment is not masked from participants or study personnel. For an endpoint involving redness, swelling, and pain, reports can be influenced by awareness of the assigned intervention, expectations, or observation practices. Standardized definitions and measurement instructions can promote consistency, but the record does not report whether assessors were independent or whether any additional steps were taken to reduce ascertainment differences.

How should a percentage endpoint be interpreted?

A percentage of participants with an event is a binary-outcome summary: each participant is classified as having or not having the event according to the endpoint definition. The denominator is important because the same event count can imply different estimated frequencies in groups of different sizes. The registry identifies the safety population as participants who received study intervention, and the adverse-event summary gives group-specific numbers at risk. It does not provide a single set of primary-endpoint numerators and denominators that resolves the several categories or time points.

The primary endpoint specifies a 95% confidence interval using the exact Clopper and Pearson method. In general, this method calculates an interval for a binomial proportion without relying on the same large-sample normal approximation used by some simpler methods. Exact intervals can be useful when event counts are small or when a proportion is near a boundary. An interval describes statistical uncertainty under the method; it does not establish that an observed difference matters clinically. The actual primary-endpoint intervals are not reported in the registry record.

Why distinguish descriptive counts from comparisons?

Counts within separate arms describe what was recorded in those groups. A comparison requires a defined contrast, such as a difference in proportions, and an analysis method specifying how uncertainty is assessed. When a trial has multiple candidate arms and more than one possible comparator, the comparison must be made explicit. The registry does not identify one primary pairwise contrast for the local-reaction endpoint or report analyses for it. Comparing counts informally across arms would not account for uncertainty, multiplicity, or differences in group denominators.

The registry lists zero analyses. Thus, the posted information does not establish that hypothesis tests, adjusted estimates, or prespecified comparisons were carried out or reported. A missing analysis result should not be interpreted as evidence of no difference.

What can the planning assumptions tell readers?

The record describes a planning illustration based on an observed effect, with 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. These are assumptions for an illustration, not evidence of the trial’s original design calculation. No resulting participant-per-arm values are stated in the record information available for this analysis, and none can be inferred. Sample-size illustrations are planning tools; they are not observed power and do not establish the probability that this completed study detected an effect.

The registry does not report the trial’s sample-size justification, target power, or a prespecified effect size. It also does not report interim analyses or rules for stopping early. Those omissions prevent assessment of whether the enrolled number was selected to answer a particular confirmatory question.

What statistical approach is used for immune-response outcomes?

The secondary outcome names serotype-specific OPA geometric mean titers one month after intervention. A geometric mean is generally used for measurements that are positive and can vary multiplicatively; it summarizes values after applying a logarithmic transformation and then returning to the original scale. The registry does not report the transformation details, handling of values below assay limits, confidence intervals, or statistical comparisons for this outcome. No numerical OPA results are reported in the record.

Overall, the methods information is sufficient to identify the endpoint scale and the stated confidence-interval procedure, but not to reconstruct the full analysis. General statistical principles can explain what these methods mean, but they cannot substitute for undocumented protocol decisions or missing outcome estimates.

10. Multiplicity, Missing Data and Analysis Populations

The study includes multiple intervention arms and multiple outcome measures. The registry identifies five outcome measures, including the primary local-reaction endpoint and a secondary OPA geometric mean titer outcome. With several groups, serotypes, outcome categories, and time points, a family of possible comparisons can arise. In general, testing many contrasts increases the chance of finding at least one apparently unusual result by chance if no adjustment or prespecified hierarchy is used.

The registry does not report a multiplicity-control procedure, a hierarchy of endpoints, or a prespecified set of primary pairwise comparisons. It also does not describe interim analyses. These details are not reported in the registry record, so it is not possible to determine how the study planned to control or interpret multiple comparisons.

Missing-data handling is also not reported in the registry record. The definition of the safety population includes participants who received study intervention, but that definition alone does not state how missing diaries, incomplete reaction assessments, withdrawals, or unavailable immune-response measurements were handled. The record does not give numbers of participants with missing endpoint data or describe imputation, censoring, or sensitivity analyses.

Because the registry lists zero analyses and does not provide a complete set of numerical primary results, readers cannot assess whether the posted results reflect all planned outcomes or how missing observations affected estimates. The distinction matters: an endpoint’s analysis population, missing-data rules, and multiplicity plan can change the interpretation of estimated percentages and uncertainty.

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: cellulitis (2.2%).

The serious-event summary reports affected participants by group and the number at risk. Candidate-5 has 1 serious event among 45 participants at risk. Each other listed group has 0 serious events: Candidate-1, Candidate-2, Candidate-3, Candidate-4, Candidate-6, Candidate Control, PCV15, and 13vPnC. The summary reports 0 deaths for all groups.

The registry also lists Cellulitis at 2.2% among the top serious-event terms. The record does not provide further detail in this summary to establish the clinical course, timing, or attribution for that term. These figures should be read as a description of events reported during the study, not as a formal test of differences between interventions.

Rare outcomes are difficult to compare reliably when few events are observed. In general, a zero count does not prove that an event cannot occur, and a nonzero count in one arm does not by itself establish a difference from another arm. The registry does not report confidence intervals or inferential comparisons for these serious-event counts. They also should not be confused with the primary endpoint, which concerns local reactions within 7 days.

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

This trial addresses early safety and immunogenicity descriptions for several pneumococcal conjugate formulations in healthy adults aged 18 through 49. The design is randomized and parallel, with open-label assignment and a single injection described for each arm. The primary endpoint focuses on local reactions over a defined period, while the secondary outcome concerns serotype-specific OPA geometric mean titers one month after intervention.

The registry record does not report a consolidated numerical result for the primary local-reaction endpoint, and it does not report numerical immune-response results. As a result, the available information cannot establish how the candidate formulations compare with Candidate Control, PCV15, or 13vPnC on either endpoint. The adverse-event summaries provide descriptive counts, but do not replace endpoint-specific analyses or uncertainty estimates.

These results also cannot establish equivalence or non-inferiority. Such conclusions require a defined comparison, a prespecified margin, and an appropriate analysis with uncertainty estimates. Those elements are not reported in the registry record. Similarly, no reported test supports a claim of statistical significance or lack of significance for the primary endpoint.

The adverse-event data indicate that serious-event counts were zero in most groups and one in Candidate-5, with zero deaths recorded across the groups. This is a description of the recorded events, not proof that serious events are absent or that risks are equal. Small numbers of observed serious events generally leave considerable uncertainty about rare outcomes.

In general, findings from a phase 1 study in healthy adults do not automatically apply to other populations or settings. The registry identifies this study population and purpose, but does not report evidence that would support extrapolation beyond it. The record is most informative about the trial’s stated design, endpoint definitions, and descriptive safety counts; it is not a complete statistical report of comparative primary or immunogenicity outcomes.

13. Why This Trial Matters Statistically

This trial illustrates why a registry record’s design details and numerical results need to be read separately. Randomization and a parallel structure describe how groups were organized, while the primary endpoint definition describes what was intended to be measured. Neither alone establishes what the trial found. A reader needs the endpoint estimates, denominators, uncertainty intervals, and prespecified contrasts to evaluate the strength and precision of evidence.

The endpoint is a percentage of participants with local reactions, and the registry names an exact confidence-interval method. That information makes clear how uncertainty was intended to be represented. Yet the lack of a consolidated primary result means that the estimation and comparison cannot be evaluated from the registry record. The distinction is important: a stated method is not the same as a reported analysis.

The multiple arms also make the choice of comparator statistically consequential. Candidate formulations, Candidate Control, PCV15, and 13vPnC create several plausible contrasts. Without a reported comparison plan or multiplicity procedure, readers should not treat informal differences among arm summaries as confirmatory findings.

The record also shows why safety counts require context. Serious events are sparse in the posted summary, while the other adverse-event counts are more numerous. These summaries refer to different event groupings and should not be substituted for the local-reaction endpoint. Reporting denominators helps make the descriptive counts interpretable, but formal comparative claims need uncertainty estimates and a stated analysis.

Finally, a planning illustration based on an observed effect should not be mistaken for the original trial design or for observed power. The registry does not report the sample-size justification or analysis plan. This limits what can be inferred about the study’s intended precision and its ability to answer a specific comparative question.

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 of the available record is that it does not provide a consolidated numerical result for the primary local-reaction endpoint, despite defining its timeframe, population, and confidence-interval method. The outcome is described across several categories or time points, and the record does not reduce it to one comparison. Numerical OPA results for the named secondary outcome are also not reported in the registry record.

The study has several arms, but the allocation ratio and randomized participant counts by arm are not reported. The adverse-event summary gives numbers at risk for its listed groups, but it does not supply endpoint-specific denominators or analysis details for the primary local-reaction outcome. The registry also does not identify a single primary comparator for that endpoint.

The record does not report the original sample-size justification, a detailed analysis plan, multiplicity handling, missing-data methods, or interim analyses. It also does not provide inferential comparisons or confidence intervals for the adverse-event summaries. These omissions limit assessment of precision, potential selection among analyses, and the role of incomplete data.

The open-label design is relevant to participant-reported symptoms such as pain, and the registry does not describe masking of outcome assessors or additional safeguards against differences in reporting. The single-injection arm descriptions and stated endpoint timeframes provide useful context, but do not answer questions about longer follow-up or outcomes outside those timeframes. Such details are not reported in the registry record.

Finally, the enrolled population consists of healthy adults aged 18 through 49. The record does not provide evidence for applying the reported safety summaries to other populations. These limitations concern the scope and completeness of the registry information and do not, by themselves, establish that the trial was conducted improperly.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of Pneumococcal Conjugate Formulations in Healthy Adults 18 Through 49 Years of Age — NCT05489328.
• Registry record last updated 2024-04-18; status last verified 2024-04.
• Results first posted 2024-04-18.
• 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

NCT05489328 is a completed, randomized, open-label, parallel phase 1 trial sponsored by Pfizer. It enrolled 394 healthy adults aged 18 through 49 to evaluate the safety and immunogenicity of pneumococcal conjugate formulations. The registry lists single-injection arms for Candidate-1 through Candidate-6, Candidate Control, PCV15, and 13vPnC.

The primary endpoint is the percentage of participants with local reactions within 7 days after intervention; the stated interval method is the exact two-sided Clopper and Pearson method. A secondary outcome concerns serotype-specific OPA geometric mean titers one month after intervention. Numerical primary-endpoint and OPA results are not reported in a form that supports a consolidated comparison.

The serious-event summary records 1 affected participant in Candidate-5 and 0 in the other listed groups, with 0 deaths in every group. The registry does not report a full statistical analysis plan, missing-data methods, multiplicity procedures, or the trial’s sample-size justification.