One Year Antibody Persistence After a Fourth Dose Boost or Two Catch-Up Doses of Novartis Meningococcal B Recombinant Vaccine Administered Starting From 12 Months of Age and Response to a Third Dose Boost or Two Catch-Up Doses Starting at 24 Months of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for One Year Antibody Persistence After a Fourth Dose Boost or Two Catch-Up Doses of Novartis Meningococcal B Recombinant Vaccine Administered Starting From 12 Months of Age and Response to a Third Dose Boost or Two Catch-Up Doses Starting at 24 Months of Age (NCT01139021), a non-randomized phase 3 study. The primary outcome is Geometric Mean Titers (GMTs) to Assess Antibody Persistence at 12 Months After a Booster Dose of rMenB+OMV NZ Vaccination..

2. Clinical Question

3. Trial Design

NCT01139021 is recorded as a phase 3, open-label, multicenter extension study of rMenB+OMV NZ. Allocation was non-randomized, masking was absent, and the study model was parallel. The registry lists enrollment as 508 and the status as completed. Meningococcal disease is the recorded condition.

The study addressed antibody persistence after a fourth dose or two catch-up doses, and responses after later booster or catch-up schedules. The primary endpoint focused on children who had received a three-dose primary series at 2, 4, and 6 months of age. One group received MMRV at 12 months along with the fourth rMenB+OMV NZ dose; the other received MMRV at 13 months, separately from the vaccine at 12 months. The primary assessment was 12 months after the booster vaccination.

Other described groups had received two catch-up doses at different ages. The record describes assessments 12 months after those doses and at intervals after later booster doses. A separate group of naive children received catch-up doses at 24 and 26 months, with assessments after vaccination. These schedules make the study a set of related immunogenicity assessments rather than a single randomized treatment comparison.

Because allocation was non-randomized and groups differed in vaccination timing and history, comparisons across groups may reflect those differences as well as any difference in antibody measurements. The registry record does not report a randomized control group or a like-for-like control comparison. It also does not report further details about the recruitment process or the rationale for the enrollment target.

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: The eligible subjects from V72P13E1 (NCT00847145) who originally participated in the open-label, immunogenicity subset of parent study V72P13 (NCT00657709) and a naïve group, at 24 months of age, who did not previously participate in V72P13 (or V72P13E1) were enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was done on Modified Intention-To-Treat (MITT) population (Primary).

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Titers (GMTs) to Assess Antibody Persistence at 12 Months After a Booster Dose of rMenB+OMV NZ Vaccination., measured over 12 months post booster (fourth) vaccination..

The primary endpoint was the geometric mean titre (GMT) measured by human serum bactericidal assay (hSBA), assessed 12 months after a fourth rMenB+OMV NZ vaccination. It was intended to describe antibody persistence in groups that had received a three-dose primary series at 2, 4, and 6 months of age. The population named for this primary analysis was the modified intention-to-treat population.

As a general statistical explanation, a GMT summarizes measurements that are analyzed on a logarithmic scale and then expressed back on the original scale. This is useful for antibody titres because such measurements are commonly distributed asymmetrically, with some values much higher than others. A GMT describes the central level on a multiplicative scale; it is not the same as an arithmetic average.

The hSBA assay measures bactericidal antibody activity in a laboratory test. In this study, the endpoint was used to quantify immunogenicity and persistence, not to count cases of meningococcal disease. The registry record gives a 95% confidence interval as the endpoint’s dispersion measure, but does not report numeric GMT estimates or confidence interval limits. Thus the endpoint definition is available, while its reported result and precision are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean titre describe?

As a general statistical explanation, antibody titres are often summarized using a geometric mean because the measurement scale can be multiplicative and the distribution can be right-skewed. The usual calculation takes logarithms of individual titres, averages those transformed values, and converts the average back to the original scale. The resulting GMT represents a central value on a multiplicative scale. It does not describe the full spread of individual responses, and it should not be read as the titre of every participant.

The registry identifies GMT as the primary parameter and a 95% confidence interval as its dispersion measure. In general, a confidence interval conveys uncertainty about an estimated population quantity under the assumptions of the analysis. It is not a range containing a stated proportion of individual participants’ titres. The actual GMT and interval limits for the primary outcome are not reported in the registry record, so neither the level nor the precision of that estimate can be interpreted.

What does the hSBA assay contribute?

The human serum bactericidal assay is the laboratory measure used for the antibody endpoint. In general, assay results provide a measurable immune response rather than a direct count of clinical disease events. Here, the registry frames the endpoint as antibody persistence after vaccination. It does not report clinical disease incidence as the primary outcome. The distinction matters: an immunogenicity measurement describes an assay result, while a clinical outcome would describe events experienced by participants.

The secondary outcomes include titre summaries, concentration summaries, threshold-based proportions, and proportions with at least a four-fold increase. These answer different questions. A GMT summarizes the central antibody level; a geometric mean concentration summarizes a concentration measure; a threshold proportion counts the share meeting a specified assay threshold; and a fold-rise proportion describes change relative to an earlier titre. The registry record does not report numeric results for these outcomes, and the thresholds are listed in the outcome descriptions rather than accompanied by reported percentages.

How does the design affect comparisons?

The study was non-randomized and open-label, with parallel groups. As a general statistical principle, randomization reduces systematic differences between groups at assignment, while non-randomized comparisons can be affected by participant characteristics, clinical decisions, or schedule differences. Open-label status means masking was absent; the registry does not describe further procedures for limiting measurement or reporting bias. These design features do not invalidate descriptive antibody measurements, but they limit how confidently between-group differences can be attributed to one schedule feature.

The primary endpoint description contrasts MMRV at 12 months concomitantly with the booster and MMRV at 13 months separately. The registry does not describe a randomized assignment to those timings or provide a formal comparison estimate. The comparison should therefore be treated as a descriptive contrast between groups with different schedules, not as a randomized causal effect.

What does the analysis population mean?

The primary analysis is identified as modified intention-to-treat (MITT). In general, an analysis population defines which participants’ data are included in an estimate. Intention-to-treat approaches are commonly intended to retain participants according to assigned groups, while modified versions can apply additional inclusion rules. The exact MITT criteria used in this study are not reported in the registry record. It is therefore not possible to determine from the record which participants were excluded from that population or how missing measurements were handled.

The registry record gives enrollment as 508, but does not report the number included in the primary endpoint analysis or the analysis-specific denominators. Enrollment and an endpoint analysis population are not necessarily identical. Without the analysis counts, the amount of available primary endpoint data and the extent of any exclusions cannot be assessed.

How should the planning illustrations be read?

General statistical explanation: a sample-size planning calculation describes the number of participants that a hypothetical design would require under stated assumptions. It is not a measure of how much power the completed trial achieved. The planning assumptions recorded for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. These are planning assumptions, not evidence that the trial used that design or analysis.

The illustrations are based on an observed effect and are not the trial’s own design justification. They should not be called observed power. The registry record does not report the trial’s sample-size justification, and the primary observed effect is not numerically reported there. Any interpretation of a planning illustration must remain separate from inference about the completed study.

Finally, the registry record does not report a statistical analysis plan, model details for the primary endpoint, transformations or adjustments used in the analysis, or a specified approach to multiplicity. General statistical methods can explain what these choices would mean, but cannot establish which choices were made in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary GMT endpoint and several secondary antibody measures. These include GMTs and geometric mean concentrations at different assessment times, proportions meeting hSBA thresholds of 1:5 and 1:8, and proportions with at least a four-fold increase in titre. Considering many outcomes can raise the chance of obtaining a nominally unusual result by chance if each is tested separately. As a general statistical principle, multiplicity procedures can control or characterize that risk, but the registry record does not report whether any such procedure was planned or used.

The registry record lists 0 analyses. It does not report a statistical analysis plan, the number of planned comparisons, any hierarchy among secondary outcomes, or whether reported inferences were adjusted for multiple testing. No assumptions about those choices can be made from the outcome list alone.

Missing-data handling is also not reported in the registry record. The primary population is named as modified intention-to-treat, but the record does not give the population criteria, endpoint-specific denominators, reasons for missing measurements, or methods for handling incomplete data. Consequently, the extent to which missing results might affect the endpoint estimate cannot be assessed.

The enrollment figure is not a substitute for an analysis denominator. The registry record does not report how many participants contributed primary endpoint measurements or whether the analysis population differed from enrollment. These reporting gaps limit assessment of both the statistical precision and the robustness of the primary result.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: oral herpes (5.6%), bronchitis (1.5%), laryngitis (1.5%), cholesteatoma (0.9%), adenoidal hypertrophy (0.9%).

The registry lists serious adverse event information for three groups: B13 15 27, B12 14 26, and B24 26. It records 2 serious adverse events among 67 at risk for B13 15 27, 1 among 18 at risk for B12 14 26, and 6 among 112 at risk for B24 26. These are the recorded group counts and denominators; they should be read as descriptive entries, not as a randomized comparison of schedules.

The registry also lists selected serious-event terms with percentages: Oral Herpes, 5.6%; Bronchitis, 1.5%; Laryngitis, 1.5%; Cholesteatoma, 0.9%; Adenoidal Hypertrophy, 0.9%; and Enteritis, 0.9%. The record does not provide further context for interpreting these terms or percentages in relation to the primary antibody endpoint. The listed percentages should not be treated as comparative risk estimates without corresponding group-specific details and a suitable design.

Death counts are not reported in the registry record. The serious adverse event entries do not establish that all events were caused by vaccination, and the record does not provide a causal attribution analysis. They should be interpreted as recorded safety information, separate from the immunogenicity results.

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

The registry record establishes that the study examined antibody persistence and response after several rMenB+OMV NZ schedules in young children. It identifies the primary outcome as hSBA GMT 12 months after a fourth dose in groups that had received a three-dose primary series. It also describes additional antibody measurements and selected serious adverse event information.

However, numeric primary GMT estimates and their 95% confidence intervals are not reported in the registry record. The same is true for the listed secondary antibody outcomes. Without those results, the antibody levels, their uncertainty, and any differences across groups cannot be evaluated from this record. Completion status alone does not supply those missing estimates.

The design also limits what a group contrast could establish. Allocation was non-randomized, masking was absent, and the groups differed in vaccine histories and timing. As a general interpretation principle, observed differences in such groups may reflect differences in the participants or schedules, not solely the feature being contrasted. The registry record does not report a formal primary comparison or an adjustment strategy.

The listed serious-event counts and terms are descriptive safety entries. They do not answer the primary immunogenicity question, and they do not establish a causal relationship between vaccination and an event. The record does not report death counts or additional analysis details needed for a comparative safety assessment.

Accordingly, the available registry information supports a description of the study’s design and intended measurements, but not a conclusion about the magnitude of antibody persistence, the precision of the primary estimate, or a causal difference between schedules. It also does not support claims about clinical protection against meningococcal disease, because the primary endpoint is an antibody assay measure and clinical disease outcomes are not reported as the primary endpoint.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a defined endpoint and a reported result. The registry record specifies a primary hSBA GMT, the assessment time, the relevant vaccination history, a confidence interval measure, and the analysis population. Those details identify what the study intended to quantify. But without the numerical estimate and interval, readers cannot judge the observed antibody level or the estimate’s precision.

The study also illustrates why design labels matter when interpreting group differences. Non-randomized parallel groups can be useful for describing responses under different schedules, but they do not provide the same protection against confounding as randomized allocation. The groups’ differing vaccination histories and MMRV timing further reinforce that contrasts need cautious interpretation.

Another statistical lesson is that immune outcomes answer distinct questions. GMTs, geometric mean concentrations, threshold proportions, and fold-rise proportions summarize different features of the response. Their definitions should not be treated as interchangeable, and a list of outcomes does not reveal which findings were strongest or most precise. The registry record does not report numeric results for these measures.

Finally, the entry shows the importance of transparent reporting about analysis populations, missing measurements, multiplicity, and sample-size rationale. The primary population is named, but its criteria and analysis denominator are not reported. The analysis plan and multiplicity handling are also not reported. This leaves substantial uncertainty about how the intended measurements were converted into inferential conclusions.

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 for interpreting efficacy-related statistics is that the registry record does not report the numeric primary GMT result or its 95% confidence interval. It also does not report numeric results for the secondary antibody outcomes. The central question can therefore be described, but its observed magnitude and precision cannot be evaluated from the registry record.

The study was non-randomized and open-label. The groups followed different vaccination schedules and histories, and the primary groups differed in MMRV timing. This makes direct causal interpretation of between-group contrasts inappropriate without additional design and analysis information. The registry record does not report a formal between-group estimate or adjustment for potential differences.

The record identifies the modified intention-to-treat population but does not state the exact inclusion criteria or the number analyzed for the primary endpoint. It does not report endpoint-specific missingness, reasons for unavailable measurements, or missing-data methods. The enrollment figure cannot establish how many participants contributed to each endpoint analysis.

The statistical analysis plan, sample-size justification, multiplicity strategy, and detailed analysis methods are not reported in the registry record. Although planning illustrations are described as based on the observed effect, they are not the trial’s design justification and should not be interpreted as observed power. The registry also does not report death counts. These omissions constrain assessment of both the immunogenicity findings and the completeness of safety reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: One Year Antibody Persistence After a Fourth Dose Boost or Two Catch-Up Doses of Novartis Meningococcal B Recombinant Vaccine Administered Starting From 12 Months of Age and Response to a Third Dose Boost or Two Catch-Up Doses Starting at 24 Months of Age — NCT01139021.
• Registry record last updated 2015-04-10; status last verified 2015-04.
• Results first posted 2015-04-10.
• 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

NCT01139021 is a completed, phase 3, open-label, multicenter, non-randomized parallel extension study of rMenB+OMV NZ, with registry enrollment of 508. The primary outcome was hSBA geometric mean titre 12 months after a fourth dose in groups that received a three-dose primary series at 2, 4, and 6 months of age. The primary analysis population was identified as modified intention-to-treat.

The record describes additional catch-up and booster schedules, multiple secondary antibody outcomes, and serious adverse event entries for three groups. It lists 15 outcome measures and 0 analyses. Numeric primary and secondary antibody results, the primary analysis denominator, missing-data methods, multiplicity handling, and the statistical analysis plan are not reported in the registry record.