Immunogenicity and Safety of BPZE1 Intranasal Pertussis Vaccine in Healthy School-age Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety of BPZE1 Intranasal Pertussis Vaccine in Healthy School-age Children (NCT05116241), a randomized phase 2 study. The primary outcome is Geometric Mean Fold Rise (GMFR) of Mucosal Immunogenicity S-IgA Against Whole Cell Extract at Day 29.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, quadruple-masked, parallel-group study. Its official title identifies it as a Phase 2b placebo-controlled randomized study, while the phase classification in the record is Phase 2. It is described as multi-center and as including both placebo and active comparators. The study status is completed, with enrollment of 368.

The three regimens allow the posted results to be read in relation to different vaccine combinations: BPZE1 with intramuscular placebo; BPZE1 with Boostrix; and intranasal placebo with Boostrix. Thus, one group received BPZE1 without Boostrix, one received both active vaccines, and one received Boostrix without BPZE1. The registry record describes the primary immunogenicity outcome for the two BPZE1-containing arms, but posted arm results also include the Boostrix comparator group.

The primary endpoint is a mucosal S-IgA geometric mean fold rise against whole cell extract at Day 29. Its stated population is the per protocol immunogenicity analysis set. The posted endpoint results list 105 participants for BPZE1 with intramuscular placebo, 113 for BPZE1 with Boostrix, and 111 for intranasal placebo with Boostrix. These endpoint denominators should not be treated as the full enrollment, nor as the number analyzed for every other outcome.

The study description states that safety follow-up continued for 6 months after the first vaccination. The registry record also lists serum and mucosal immunogenicity measures, reactogenicity and adverse events, and colonization in a substudy. Further details about allocation procedures, masking implementation, site structure, eligibility criteria, and the full visit schedule 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.

Study

Reasons for not completing this period:

Optional Attenuated Challenge Substudy

Analysis population for the primary outcome, as defined in the registry: Per protocol immunogenicity analysis set

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Fold Rise (GMFR) of Mucosal Immunogenicity S-IgA Against Whole Cell Extract at Day 29, measured over Day 29.

The primary endpoint is the geometric mean fold rise (GMFR) in mucosal secretory IgA, or S-IgA, against whole cell extract, measured at Day 29. It is reported separately for treatment arms and uses a 95% confidence interval. The analysis population is the per protocol immunogenicity analysis set.

A fold-rise measure describes the change in an antibody measure relative to its starting level. A geometric mean summarizes fold changes on a multiplicative scale, which is often useful when individual immune measurements are skewed and changes are naturally expressed as ratios. This is a general explanation of the measure; the registry record does not give the precise calculation procedure, including any transformation or handling of values below assay limits.

Mucosal S-IgA is an immune marker measured at a mucosal site. The study description frames the vaccine evaluation around immunogenicity and safety, and its brief summary says the vaccine is intended to prevent nasopharyngeal colonization and pertussis disease. The endpoint itself is an antibody response, not a direct measure of disease prevention or clinical protection. A larger fold-rise estimate describes a greater average relative rise in this immune measure within the stated analysis population; it does not on its own establish the meaning of that response for illness or transmission.

Day 29 identifies the time point for the primary outcome. The record does not report a later primary immunogenicity assessment, a threshold for a clinically meaningful response, or a validated relationship between this outcome and protection.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a geometric mean fold rise, a summary designed for measurements whose changes are naturally expressed as folds or ratios. In a general statistical explanation, a geometric mean is obtained by working on a logarithmic scale, averaging there, and transforming back. This can make a summary less dominated by a small number of unusually large values than an arithmetic mean of raw fold changes. The registry record reports the geometric mean fold rise but does not describe the exact computation, baseline handling, assay processing, or any rules for values outside the measurable range.

What does a confidence interval communicate?

Each arm estimate is accompanied by a 95% confidence interval. In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval on the same scale, while the interval limits mark values compatible with the data and method at the stated confidence level. It is not a guarantee that the true value lies within the particular interval, and it does not by itself measure clinical importance.

The posted intervals are 3.1 to 4.7 for BPZE1 with intramuscular placebo, 2.9 to 4.3 for BPZE1 with Boostrix, and 1.0 to 1.5 for intranasal placebo with Boostrix. These intervals describe uncertainty in separate arm summaries. To assess a comparative question, the most direct statistical quantity would ordinarily be an estimate of the contrast between arms, with its uncertainty and a test or other inferential procedure specified. Those comparative results are not reported in the registry record. Comparing the separate interval limits by eye does not account for the uncertainty in a contrast in the same way.

Why distinguish an arm estimate from a treatment contrast?

An arm-specific GMFR summarizes the response within that arm. A treatment contrast instead addresses how outcomes differ between groups under the chosen analysis. Even when the arm estimates look different, the statistical uncertainty of their difference depends on the variability and relationship between the estimates and on the analysis method. Those details cannot be reconstructed from the arm summaries alone. In particular, no new difference, ratio, or p-value should be inferred from the posted figures.

The randomized parallel-group design supports comparison of assigned regimens, but the record’s primary endpoint is explicitly described for the per protocol immunogenicity analysis set. Per protocol analyses can exclude participants who do not meet specified criteria. In general, such an analysis may describe responses among participants meeting the protocol requirements, while an analysis of all randomized participants answers a different question and can preserve the original randomized comparison. The criteria for this study’s per protocol set and any complementary analysis are not reported in the registry record.

What does the endpoint population mean for interpretation?

The reported denominators differ by arm: 105, 113, and 111. Those counts belong to the primary endpoint results, not necessarily to safety analyses or other immunogenicity endpoints. Enrollment was 368, but the registry record does not provide a participant flow accounting for the difference between enrollment and endpoint denominators. It also does not report how missing endpoint values were handled, whether imputation was used, or whether sensitivity analyses assessed alternative missing-data assumptions.

Missingness matters because an analysis of observed measurements may be biased if the chance of having a result is related to the participant’s response or other relevant features. This is a general statistical concern, not evidence that such bias occurred in this trial. Without reasons for missing data and the analysis procedures, the direction or size of any possible effect cannot be assessed from the registry record.

How should sample-size calculations be understood?

Any sample-size illustration based on an observed effect is a planning exercise, not a description of the trial’s original design or an estimate of observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. The record says that non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations give a total number of events. The calculated planning values and the effect fractions are not reported in the registry record described for this analysis.

These assumptions are not evidence that the trial was designed using them. The protocol’s sample-size justification, target power, anticipated effect, allowance for attrition, and any planned sample-size re-estimation are not reported in the registry record. A planning illustration using observed data can be useful for exploring what a future study might require under specified assumptions, but it should not be described as the power achieved by the completed trial.

Why can variability affect the analysis?

Immune measurements can vary substantially between participants. In general, greater variability reduces precision and makes estimates less certain for a given amount of information. A logarithmic analysis can be appropriate for multiplicative measurements, but its validity depends on the distribution and analysis assumptions. The posted summary statistics do not give participant-level variability, the model used, covariate adjustments, or diagnostic checks. These analytical details are not reported in the registry record.

Overall, the record supplies arm-level estimates and confidence intervals for the primary endpoint but not enough detail to reproduce the analysis or evaluate all of its assumptions. The numerical results should therefore be interpreted as the posted summaries for the stated endpoint population, with the limitations of absent comparative and analytic details kept in view.

10. Multiplicity, Missing Data and Analysis Populations

The study lists multiple immunogenicity and safety outcomes, including serum IgG and IgA measures, mucosal S-IgA measures, reactogenicity and adverse events, and colonization in a substudy. The registry record lists 10 outcome measures and 8 posted secondary outcomes. Testing many outcomes or time points can increase the chance of a seemingly notable result arising by chance. In general, multiplicity can be addressed by prespecifying a primary outcome, using a testing hierarchy, adjusting significance thresholds, or emphasizing estimation rather than isolated p-values.

The record identifies the Day 29 mucosal S-IgA GMFR as the primary endpoint, but a multiplicity strategy for the primary and secondary outcomes is not reported in the registry record. The number and ordering of planned comparisons, any family-wise error or false-discovery procedure, and any hierarchy among outcomes are also not reported. The registry record contains no posted analyses for a two-arm comparison, so the arm summaries should not be read as a set of confirmed pairwise findings.

The primary population is the per protocol immunogenicity analysis set. The record does not describe the inclusion criteria for that set, an intention-to-treat immunogenicity analysis, or the handling of participants with missing endpoint measurements. It also does not report reasons for missing data, imputation procedures, or sensitivity analyses. These omissions limit assessment of how closely the analyzed participants represent all randomized participants and whether missing observations could affect the estimated responses.

Likewise, the protocol’s statistical analysis plan, interim analyses, and any changes to planned outcomes or analyses are not reported in the registry record. Absence of those details does not show that a particular procedure was or was not used; it means the posted record does not permit that assessment.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (0.8%), campylobacter gastroenteritis (0.8%), dyspnea (0.8%).

The registry lists safety counts for all participants post-vaccination and for optional substudy participants post-challenge. These are distinct groups and should be read separately. Among all participants post-vaccination, the serious-event counts are 1 among 123 for BPZE1 with intramuscular placebo, 0 among 121 for BPZE1 with Boostrix, and 2 among 122 for intranasal placebo with Boostrix. Deaths are listed as 0 in each of these groups.

For optional substudy participants post-challenge, serious-event counts are 0 among 38, 0 among 36, and 0 among 46, in the same treatment order. Deaths are listed as 0 in each substudy group. The registry also lists appendicitis, Campylobacter gastroenteritis, and dyspnea as serious-event terms, each at 0.8%. The record does not assign these listed terms to a particular treatment group in the posted summary.

These counts do not describe event timing, duration, relatedness to vaccination, or severity beyond the registry’s serious-event classification. No inference about comparative safety should be made from the small number of serious events alone. In general, rare events are estimated imprecisely, and differences in counts can arise from chance. The record also lists other adverse events, but the count summaries do not provide a complete clinical account of each event or participant.

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

The primary endpoint results describe mucosal S-IgA fold rise at Day 29 among participants in the per protocol immunogenicity analysis set. The reported GMFR is 3.8 for BPZE1 with intramuscular placebo, 3.5 for BPZE1 with Boostrix, and 1.2 for intranasal placebo with Boostrix. Their corresponding 95% confidence intervals are 3.1 to 4.7, 2.9 to 4.3, and 1.0 to 1.5. These values characterize the posted antibody-response summaries, not clinical outcomes.

They do not establish whether any regimen prevents pertussis, reduces nasopharyngeal colonization, or provides clinical protection. Although the study description states that BPZE1 is intended to prevent colonization and pertussis disease, the primary endpoint is an immune marker. The registry record does not give a validated correlate of protection or a threshold for interpreting these GMFR values as a level of protection.

The arm-level summaries also do not, on their own, establish a statistically significant difference between regimens. No direct comparative estimate, p-value, or adjusted analysis for the primary endpoint is reported in the registry record. The separate confidence intervals are useful for describing precision, but they are not a substitute for inference on a prespecified contrast. The record does not report the analysis plan, multiplicity approach, or full handling of missing measurements, all of which matter when assessing confirmatory claims.

The endpoint denominators are smaller than the total enrollment, and the analysis population is per protocol. Without participant flow and missing-data details, the extent to which these estimates represent all randomized children cannot be assessed. The findings are specific to the studied healthy school-age children, the regimens described, the mucosal antibody measure, and the Day 29 assessment. The registry record does not provide a basis for extrapolating to other ages, populations, outcomes, or follow-up periods.

The safety counts are descriptive. A small number of serious events and no listed deaths in these groups do not establish absence of risk, nor do they determine whether one regimen is safer than another. Interpretation requires attention to the study’s size, follow-up, event definitions, and the uncertainty around uncommon outcomes.

13. Why This Trial Matters Statistically

This trial is statistically informative as a comparison of three related regimens within a randomized parallel-group study. The groups separate an intranasal BPZE1 regimen from a Boostrix regimen and include a group receiving both. That structure makes the arm-specific immune response summaries relevant to different vaccine combinations, while the randomized design provides a framework for comparing assigned groups.

The primary endpoint also illustrates the distinction between an immune-response measure and a clinical outcome. A fold-rise summary can capture relative change in a mucosal antibody measure, and its confidence interval communicates uncertainty. But its interpretation as protection depends on evidence beyond the endpoint value itself. The registry record does not report a validated clinical threshold or a direct link between this measure and disease prevention.

Statistically, the posted results invite careful separation of estimation from hypothesis testing. The arm-specific GMFR estimates and their confidence intervals describe the observed response summaries. They do not supply a formal contrast, and they do not reveal a multiplicity strategy or the details of the analysis model. Readers can recognize the pattern in the arm estimates without treating it as a confirmed between-group effect.

The study also highlights the importance of analysis populations. Enrollment was 368, while the primary endpoint has arm-specific denominators of 105, 113, and 111 in the per protocol immunogenicity set. The registry record does not explain participant flow or missing measurements. Those details are important when judging precision and the scope of conclusions.

Finally, immunogenicity and safety are both listed, but the posted primary result cannot answer every question raised by the study. Secondary outcome results and colonization substudy findings are not fully available in the registry record. The statistical value of the record lies in what it can describe clearly, alongside explicit limits on comparative and clinical interpretation.

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 arm-specific primary endpoint estimates and 95% confidence intervals, but does not report a formal comparison between treatment arms. It does not give the primary hypothesis test, a comparative effect estimate, an adjustment for covariates, or the statistical model used. As a result, the strength and precision of a direct treatment contrast cannot be assessed from the posted summaries.

The primary endpoint population is per protocol. Criteria for inclusion in this set, participant flow by arm, and reasons for exclusion are not reported in the registry record. The endpoint denominators therefore cannot be reconciled with total enrollment from the information posted. Missing-data handling, assay failure rules, and sensitivity analyses are also not reported.

The record does not state the sample-size justification, target statistical power, planned effect size, or any interim analysis plan. Any sample-size planning illustrations based on the observed effect should not be taken as the trial’s design rationale or observed power. The multiplicity approach for multiple immunogenicity and safety outcomes is not reported.

The primary result concerns a Day 29 mucosal antibody measure. The registry record does not report a threshold for clinical relevance, a validated correlate of protection, or a direct clinical efficacy outcome within this primary endpoint. Although the study description refers to intended prevention of colonization and disease, the posted primary result alone cannot establish either. The complete results for secondary outcomes and the colonization substudy are not reported in the registry record.

Safety summaries are counts for specified post-vaccination and post-challenge groups. The record does not provide detailed event narratives, timing, relatedness, or comparative uncertainty for uncommon events. Consequently, the safety figures are descriptive and do not support a definitive comparative safety conclusion.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety of BPZE1 Intranasal Pertussis Vaccine in Healthy School-age Children — NCT05116241.
• Registry record last updated 2025-11-06; status last verified 2025-10.
• Results first posted 2025-11-06.
• 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.

18. Record Summary

The registry record describes a completed randomized, quadruple-masked, parallel-group Phase 2 study of BPZE1 in healthy school-age children, with enrollment of 368. Its official title identifies the study as Phase 2b. The three regimens were BPZE1 with intramuscular placebo, BPZE1 with Boostrix, and intranasal placebo with Boostrix. The study description states that safety follow-up continued for 6 months after the first vaccination.

The primary endpoint was day-29 mucosal S-IgA geometric mean fold rise against whole cell extract in the per protocol immunogenicity analysis set. Posted GMFR estimates were 3.8, 3.5, and 1.2 across the three arms, with 95% confidence intervals of 3.1 to 4.7, 2.9 to 4.3, and 1.0 to 1.5, respectively. No formal between-arm analysis is reported in the registry record.

Safety counts include serious events and deaths for post-vaccination groups and optional substudy participants post-challenge. Details on missing data, analysis methods, multiplicity, and the study’s sample-size justification are not reported in the registry record.