Safety, Tolerability, and Immunogenicity Study of a 24-Valent Pneumococcal Conjugate Vaccine (VAX-24) in Older Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, and Immunogenicity Study of a 24-Valent Pneumococcal Conjugate Vaccine (VAX-24) in Older Adults (NCT05297578), a randomized phase 2 study. The primary outcome is Percentage of Participants Reporting Solicited Local Reactions Within 7 Days After Vaccination.

2. Clinical Question

The study also evaluates safety and tolerability and includes secondary immune-response outcomes: serotype-specific OPA geometric mean titers and serotype-specific IgG geometric mean concentrations. These are distinct questions from the primary local-reaction question. The posted results do not provide values for those immune outcomes, so they cannot be interpreted from the registry record.

The comparison is between dose groups in a randomized, controlled study, not a comparison of vaccination with no vaccination. The registry describes a dose-finding study in healthy older adults; it does not establish that the groups were intended to represent every older adult population or clinical setting.

3. Trial Design

This was a randomized, parallel-group, controlled Phase 2 study of the safety, tolerability, and immunogenicity of VAX-24 in healthy adults 65 years and older. The registry lists enrollment as 207 and the study status as completed. The recorded start date is 2022-06-15, and the primary completion date is 2023-02-15.

Four groups are described: VAX-24 low dose, VAX-24 mid dose, VAX-24 mixed dose, and PCV20. Each group received a single intramuscular injection on Day 1. The registry identifies the study as quadruple-masked and observer-blind. It does not further describe who was masked or how masking was maintained.

The stated objective was to evaluate the safety and tolerability of a single injection of VAX-24 at 3 dose levels compared with PCV20. The primary outcome concerns solicited local reactions during the 7 days after vaccination. Secondary outcomes concern pneumococcal serotype-specific immune measures. Although the registry lists those outcome types, numerical results for the immune measures are not reported in the registry record.

The registry record does not report the randomization procedure, allocation ratio, eligibility criteria beyond the description of healthy adults 65 years and older, or the planned analysis methods in enough detail to reconstruct them. Those omissions limit how fully the design and analysis can be assessed from the record alone.

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: 230 participants were screened; 21 did not meet eligibility criteria and 2 were excluded for other reasons. 1 participant was randomized to VAX-24 2.2 mcg but was administered and included in the analysis for VAX-24 2.2/4.4 mcg dose. 1 participant in the PCV20 group was lost to follow up at day 1 without any solicited or unsolicited AEs collected. A 66-year-old male did not finish due to sudden cardiac death not considered related to vaccine due to risk factors of hypertension and BMI=47.4

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population, defined as all participants exposed to study 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.

Population: Randomized population

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Reporting Solicited Local Reactions Within 7 Days After Vaccination, measured over 7 days after vaccination.

The primary endpoint is the percentage of participants reporting solicited local reactions within 7 days after vaccination. The listed reactions are redness/erythema, swelling/induration, and pain at the injection site. The endpoint uses the safety population, defined as all participants exposed to study vaccine.

A percentage is a way to express how commonly an event was reported within a defined group. For a safety endpoint, this makes the observed frequency of reactions interpretable in relation to the number of exposed participants. The specified observation window also identifies the period in which reactions were solicited; it does not describe reactions outside that window.

Local reactions are relevant to a vaccine safety and tolerability assessment because they capture reported responses at the injection site after vaccination. The registry endpoint, however, combines several reaction types, and the posted record does not provide a single numerical result for this endpoint. A category-by-category or time-point-specific account is not reported in the registry record in a form that supports one overall comparison. Consequently, the primary endpoint’s observed percentages and precision cannot be assessed from the record alone.

The endpoint is not an immune-response measure. OPA geometric mean titers and IgG geometric mean concentrations are listed separately as secondary outcomes, and their results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

These results are most naturally read as a randomized-group safety comparison with a binary outcome: a participant either reported an event in the defined period or did not. A percentage expresses the observed proportion of participants with an event. The denominator matters because it identifies how many exposed participants contributed to that proportion. The primary endpoint’s stated population is the safety population, defined as all participants exposed to study vaccine.

What does randomization contribute?

In general, random assignment is intended to make groups comparable, on average, with respect to factors present before treatment assignment. It provides a basis for comparing outcomes between assigned groups, but it does not guarantee that every realized group is identical in size or characteristics. The registry identifies this study as randomized and parallel-group. The randomization method, allocation ratio, and details of implementation are not reported in the registry record, so those features cannot be evaluated further.

How should a percentage be interpreted?

A reported percentage describes the observed frequency in the analyzed group; it is not automatically a measure of the underlying frequency in all people who might receive a vaccine. In general, a confidence interval conveys the range of values compatible with the observed data under the statistical method used. It helps communicate precision: a more uncertain estimate should not be read as if it were exact. Confidence intervals for the primary local-reaction results are not reported in the registry record, and no single primary percentage is available for interpretation.

The outcome includes redness/erythema, swelling/induration, and injection-site pain. When an endpoint includes multiple event categories or time points, a combined percentage and separate category-specific percentages answer different questions. A combined value can conceal variation across components, while separate values require attention to the number of comparisons being made. The registry record notes that the primary outcome has several categories or time points and does not reduce it to one comparison.

What do the safety counts show?

The serious adverse-event counts are small descriptive totals in the four groups. Counts can identify what was recorded, but the count alone does not show whether events were caused by study treatment or whether differences between groups exceed what might occur by chance. A comparative assessment would require clearly defined outcomes, suitable statistical methods, and uncertainty estimates. Those details are not available for the serious-event counts in the registry record. The same caution applies to the counts of other adverse events.

The registry also lists percentages beside several serious-event terms. Those entries are reported as Sudden cardiac death, 2.0%; Urinary tract infection, 1.9%; Uterine Cancer, 1.9%; Hysterectomy, 1.9%; Pneumonia, 1.9%; and Heart rate irregular, 1.9%. The record does not explain the denominators or the method used for these term-level percentages, nor does it connect each listed term to a particular treatment group. They should therefore be read as registry entries, not as group-specific comparative risks.

What does the planning illustration mean?

In general, a sample-size planning calculation describes the number of participants needed under specified assumptions to target a chosen statistical power for a planned effect. The registry’s stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it defines the target effect as a stated fraction of the observed effect. It is described as a planning illustration computed from the observed effect, not as the trial’s own design.

Such an illustration is conditional on its assumptions and does not establish the study’s actual power after completion. It is not observed power, and it does not replace estimates of the outcomes and their precision. The record does not report the trial’s sample-size justification, so the illustration should not be interpreted as the rationale used to plan enrollment.

For count or percentage outcomes, uncertainty depends on the number of participants and how frequently the event occurs. General statistical methods can account for this uncertainty, but the registry record does not report the specific inferential analysis, confidence intervals, or adjusted comparisons for the primary local-reaction endpoint. The number of analyses is listed as zero. That means the posted record does not furnish a set of statistical tests that can be evaluated for assumptions, multiplicity handling, or model fit.

10. Multiplicity, Missing Data and Analysis Populations

The study includes a primary local-reaction outcome and secondary immunogenicity outcomes involving serotype-specific OPA geometric mean titers and IgG geometric mean concentrations. Multiple outcomes, reaction categories, time points, or serotypes can create multiplicity: the more comparisons considered, the greater the chance that some results appear noteworthy by chance alone. In general, a prespecified analysis plan can clarify which outcomes are confirmatory and whether any adjustment or hierarchy is used. Such a plan and any multiplicity procedure are not reported in the registry record.

The registry lists zero analyses. It does not report a statistical analysis plan, the handling of missing observations, imputation methods, or sensitivity analyses. The primary endpoint specifies the safety population as all participants exposed to study vaccine, but the record does not explain how missing reaction reports or incomplete follow-up within the 7-day period were treated. It also does not report endpoint-specific analyzed denominators for the local reactions.

These omissions matter because a percentage can depend on who is included and how incomplete observations are handled. The safety population definition gives a broad inclusion rule based on exposure, but it does not answer every question about endpoint-level data completeness. The registry record also does not report whether analyses were adjusted for baseline characteristics or how any subgroup analyses were selected. Without those details, the posted counts are best interpreted descriptively, and the exact analytical choices cannot be reconstructed.

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: sudden cardiac death (2.0%), urinary tract infection (1.9%), uterine cancer (1.9%), hysterectomy (1.9%), pneumonia (1.9%).

The serious adverse-event counts are 1 in the VAX-24 low-dose group, 1 in the VAX-24 mid-dose group, 1 in the VAX-24 mixed-dose group, and 0 in the PCV20 group. The corresponding at-risk counts are 52, 51, 53, and 50. The registry also records 1 death in the VAX-24 mid-dose group and 0 in each of the other groups.

These figures describe what the registry record reports; they do not establish causation. The record does not report whether the serious events or death were considered related to vaccination, or provide enough clinical detail to interpret their circumstances. A count of zero in a group means no such event is recorded for that group in this entry, not that the event is impossible.

The listed serious-event terms and percentages do not identify treatment groups or explain their denominators in the registry record. They should not be read as group-specific rates. The separate counts of other adverse events also do not indicate severity, relatedness, or whether a participant could have more than one event. These limitations make the counts useful as a descriptive safety record but insufficient for a causal or comparative conclusion.

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

The posted data establish the basic design and describe several safety counts for a randomized Phase 2 study in healthy adults 65 years and older. They show that the study compared three VAX-24 dose groups with PCV20 after a single injection. They also show the recorded serious adverse-event counts, other adverse-event counts, and deaths by group. These are observations from the registry record, not estimates of treatment effect with reported uncertainty.

The record does not provide a single numerical result for the primary endpoint of solicited local reactions within 7 days. It therefore does not allow a reader to assess the observed percentage in each group or the precision of a group comparison. The secondary immune-response outcomes are named but their numerical results are not reported in the registry record. No efficacy conclusion follows from the safety counts or from the stated study objective.

One serious adverse event was recorded in each VAX-24 dose group, none in the PCV20 group, and one death was recorded in the VAX-24 mid-dose group. These counts alone do not establish that vaccination caused an event or death, or that groups differ in underlying risk. The registry entry does not provide the attribution, event timing, statistical comparison, or uncertainty needed to answer those questions.

The study’s completed status does not resolve these evidentiary gaps. A completed trial can have results that are incompletely reported in a registry record. Interpretation should stay within the available descriptive information and should not substitute missing endpoint estimates or analysis details with assumptions.

13. Why This Trial Matters Statistically

This study raises several useful statistical issues in a compact dose-finding setting. It compares three VAX-24 dose groups with an active vaccine comparator and focuses on both local safety outcomes and immunogenicity. Those outcome types answer different questions: the primary endpoint records solicited local reactions, whereas the secondary outcomes concern serotype-specific immune measures. Keeping them distinct avoids treating a safety observation as if it were an immune-response result.

The primary endpoint is a percentage, but the registry does not present one numerical result for it. The stated reason is that the outcome involves several categories or time points and was not reduced to one comparison. This illustrates why outcome definitions, component-level reporting, and a clearly identified primary contrast matter: without them, readers cannot see the group-specific frequencies or evaluate precision.

The study also illustrates the distinction between planned sample size and observed evidence. A planning illustration based on an observed effect and stated assumptions is not the study’s design justification and is not observed power. Statistical interpretation depends instead on the actual outcome estimates, denominators, and measures of uncertainty. Those are not reported for the primary endpoint in this record.

Finally, serious adverse-event counts need context. Event attribution, definitions, timing, and analytic methods affect what can be inferred, and the registry record does not report enough of these details for a causal interpretation. Careful separation of description from inference is therefore central to reading these results.

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 registry record gives a limited account of the primary outcome results. It identifies solicited local reactions and a 7-day timeframe, but does not report a single numerical percentage or a clear numerical comparison across groups. The outcome includes several reaction categories or time points, and results by category or time point are not available in a form that supports a complete assessment of the endpoint.

Although the study is described as randomized, parallel, and quadruple-masked, the registry does not report the randomization procedure, allocation ratio, masking implementation, or detailed eligibility criteria. It does not give the sample-size justification, planned statistical analysis, multiplicity approach, missing-data methods, or sensitivity analyses. These omissions prevent a full appraisal of the intended and completed analyses.

Safety information is also limited. The record gives counts of serious and other adverse events and records a death, but does not report event relatedness, timing, severity details, or enough information to determine how term-level percentages were calculated. The listed serious-event terms are not linked to treatment groups in the available entry.

Finally, the secondary immune outcomes are named but their results are not reported in the registry record. The reported enrollment and completion status do not fill these gaps. The findings described in the registry should therefore be treated as incomplete descriptive information rather than a comprehensive account of trial outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Tolerability, and Immunogenicity Study of a 24-Valent Pneumococcal Conjugate Vaccine (VAX-24) in Older Adults — NCT05297578.
• Registry record last updated 2024-10-09; status last verified 2024-09.
• Results first posted 2024-04-16.
• 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

NCT05297578 is a completed randomized, quadruple-masked, parallel-group Phase 2 study sponsored by Vaxcyte, Inc. It enrolled 207 healthy adults 65 years and older and compared three single-injection VAX-24 dose groups with PCV20. The recorded start date is 2022-06-15, and the primary completion date is 2023-02-15.

The primary endpoint is the percentage reporting solicited local reactions within 7 days after vaccination. The registry does not report a single numerical result for that endpoint. It records serious adverse-event counts of 1, 1, 1, and 0 across the low-dose, mid-dose, mixed-dose, and PCV20 groups, respectively, and one death in the mid-dose group. These are descriptive entries and do not establish causation. Numerical results for the listed secondary immune outcomes are not reported in the registry record.