Safety and Immunogenicity of Novartis Meningococcal B Vaccine When Administered to Immunocompromised Children and Adolescents Compared to Healthy Subjects.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of Novartis Meningococcal B Vaccine When Administered to Immunocompromised Children and Adolescents Compared to Healthy Subjects. (NCT02141516), a non-randomized phase 3 study. The primary outcome is Percentages of Subjects With Serum Bactericidal Activity Using Human Complement (hSBA) Titers ≥ 5 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain..

2. Clinical Question

3. Trial Design

This was a Phase IIIb, open-label, controlled, multicenter study with a parallel-group structure. Allocation was non-randomized. The registry record lists three study arms: participants with complement deficiency, participants with asplenia or splenic dysfunction, and age-matched healthy controls. It describes the healthy subjects as a descriptive control group for immunogenicity and safety.

The study concerned children and adolescents from 2 to 17 years of age who were considered at increased risk of meningococcal disease because of primary or secondary complement deficiencies, asplenia, or splenic dysfunction. The intervention was rMenB+OMV NZ. The planned vaccination schedule described in the primary endpoint information was two doses, on Day 1 and Day 61. The primary immune-response assessment was scheduled for Day 1 and Day 91, with Day 91 defined as one month after the second dose.

The record gives an enrollment of 239 and reports the study status as completed. The recorded start was 2014-05, and primary completion was 2015-03. These dates describe the registry record; they do not establish when every participant completed follow-up or when all analyses were finalized.

Because treatment assignment was not randomized, differences between the risk-condition groups and healthy controls cannot be interpreted as if they arose from random allocation. Health status itself defines the groups, and other differences between them may also influence measured immune responses or safety outcomes. The record does not report the matching procedure, detailed baseline characteristics, or an adjusted comparison strategy. It also does not report a statistical plan for controlling confounding. The study design therefore supports descriptive comparisons, but the record does not establish that group differences would represent a causal effect of health status or vaccination.

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: All the enrolled subjects were included in the trial. One subject did not complete the study because he/she did not meet criteria for re-vaccination; two subjects met enrollment delay criteria since they required regular blood transfusions and they were unable to commit to visit windows (screen failure).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was done on Full Analysis Set (all subjects in the enrolled set who: received a study vaccination and provided an evaluable serum sample at 1 month after the second dose of rMenB+OMV NZ, with assay result available for at least one of the serogroup B indicator strains or M10713 strain or ELISA).

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 Percentages of Subjects With Serum Bactericidal Activity Using Human Complement (hSBA) Titers ≥ 5 for B Indicator Strains (H44/76, 5/99, and NZ98/254) and M10713 Strain., measured over Day 1 and Day 91 (one month after the second dose of the study vaccine).

The primary endpoint is the percentage of subjects whose serum bactericidal assay using human complement (hSBA) reached a titer of at least 5 against the listed meningococcal serogroup B strains: H44/76, 5/99, NZ98/254, and M10713. The assessment times were Day 1 and Day 91; the latter is described as one month after the second vaccine dose. The vaccine doses were administered on Day 1 and Day 61.

An hSBA titer is an assay-based measure of bactericidal activity in serum using human complement. The endpoint converts each participant’s assay result into a threshold classification: the titer either meets the specified threshold or does not. Reporting the percentage above that threshold gives a group-level description of the proportion meeting the endpoint, rather than a description of the exact titer distribution for every participant.

This type of endpoint is used to characterize an immune response to vaccination. It is not itself a clinical disease outcome. The registry record specifies a 95% confidence interval as the dispersion measure, but the numerical percentages and intervals are not reported in the registry record. It therefore does not permit assessment of the estimated response level or its precision for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: an assay result either meets the hSBA threshold of at least 5 or it does not. A group percentage summarizes the proportion of evaluated participants who meet that threshold. The registry specifies a 95% confidence interval for this percentage. A confidence interval expresses statistical uncertainty around an estimate; a narrower interval generally indicates greater precision, while a wider interval indicates less precision. The registry record does not report the numerical endpoint estimates or intervals, so their precision cannot be assessed.

What does the assay threshold represent?

The assay uses human complement and measures serum bactericidal activity against the named meningococcal strains. The endpoint focuses on whether the measured titer reaches the prespecified threshold, rather than on the full range of assay values. Threshold outcomes are useful for summarizing how many participants meet a defined immune-response criterion, but they discard information about how far values lie above or below the threshold. The record does not report continuous titer summaries or the numerical percentages for the threshold endpoint.

What does non-randomized allocation imply?

In a randomized study, allocation can help balance measured and unmeasured characteristics between comparison groups on average. This study was non-randomized: the principal groups were defined by complement deficiency, asplenia or splenic dysfunction, or healthy status. Consequently, comparisons are descriptive and may be affected by differences between these populations. Age matching is mentioned for the healthy controls, but the matching method and any additional adjustment are not reported in the registry record. Statistical adjustment, if any, cannot be assumed.

How should the confidence intervals be read?

A confidence interval is an estimate of the range of values compatible with the observed data under the method used. It is not a guarantee that the true value lies inside a particular interval, and it does not by itself establish a causal explanation for an observed difference. For this study, the interval measure is specified, but the actual interval limits and the calculation method are not reported in the registry record. No conclusion about the strength of evidence can be drawn from the endpoint description alone.

What can sample-size illustrations tell readers?

Any planning illustrations associated with these results are based on an observed effect and are not the study’s original design justification. The stated 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. For time-to-event outcomes, the stated approach gives a total number of events using the Schoenfeld method; other outcomes are expressed as participants per arm. These are planning illustrations, not observed power, and they do not demonstrate that the completed study had adequate power. The registry record does not report its own sample-size justification or the assumptions used when planning enrollment.

What analysis details are unavailable?

The registry record identifies the primary population as a Full Analysis Set, described as including enrolled subjects who received a study vaccination and provided an evaluable serum sample one month after the second dose, with an assay result available for at least one listed strain. The complete population definition and additional handling rules are not reported in the registry record. The record does not report the statistical model, adjustment variables, method for calculating confidence intervals, or a detailed analysis plan. These omissions limit reproducibility and prevent readers from determining whether reported analyses addressed the non-randomized group structure.

Over-dispersion is a general concern when observations vary more than a simple statistical model expects. For a binary endpoint, differences in participant characteristics or clustering can make uncertainty larger than a basic model would suggest. Whether this issue was assessed or addressed in this study is not reported in the registry record. The record also does not report interim analyses or stopping rules, so none should be inferred from the completed status.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures. When a study evaluates multiple outcomes, strains, time points, or subgroup comparisons, the chance of at least one apparently unusual result can increase if many statistical tests are performed. This general issue is called multiplicity. The primary endpoint names several strains and two assessment times, but the registry record does not report whether multiplicity adjustments or a hierarchy among endpoint tests were used. It also does not report a detailed statistical analysis plan. No claim about control of false-positive findings can therefore be made.

The primary population is described as a Full Analysis Set. It includes enrolled subjects who received a study vaccination and provided an evaluable serum sample one month after the second dose, with an assay result available for at least one of the named strains. The registry record does not report the number of participants included in each primary analysis, how missing serum samples or unevaluable assays were handled, or whether any sensitivity analyses were conducted. The exact analysis-population definition is not fully detailed in the record.

Missing measurements can affect a percentage estimate if participants without an evaluable result differ from those with results. The amount and pattern of missing primary endpoint data, and any method used to address them, are not reported in the registry record. The record lists 0 analyses, so numerical inferential analysis results are not available there. These limitations leave uncertainty about how the planned endpoints were analyzed and how robust any estimate would be to missing observations or multiple testing.

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: respiratory tract infection viral (2.5%), intracardiac thrombus (0.9%), appendicitis (0.9%), gastroenteritis salmonella (0.9%), tonsillitis (0.9%).

The registry record reports serious adverse-event counts for the CompDef, Asplenia, CompDef + Asplenia, Healthy, and Total categories. The corresponding numbers affected are 1, 5, 6, 0, and 6, with respective numbers at risk of 40, 110, 150, 87, and 237. These are counts from the registry record and should be read with their listed categories; they should not be added together or treated as independent comparisons.

The record also lists other adverse-event counts: 39 among 40 at risk for CompDef, 106 among 110 for Asplenia, 145 among 150 for CompDef + Asplenia, 87 among 87 for Healthy, and 232 among 237 for Total. The registry record does not provide a causal assessment for these events, so these counts alone do not show whether an event was caused by vaccination. Deaths are not reported in the registry record.

The listed serious-event terms include RESPIRATORY TRACT INFECTION VIRAL at 2.5%; INTRACARDIAC THROMBUS, APPENDICITIS, GASTROENTERITIS SALMONELLA, TONSILLITIS, and CONCUSSION at 0.9% each. The record does not give further context about event attribution or how these terms were selected. These figures describe reported events and are not, by themselves, evidence of a treatment effect.

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

The study addresses an immune-response and safety question for rMenB+OMV NZ in children and adolescents with complement deficiency or asplenia/splenic dysfunction, using age-matched healthy subjects as descriptive controls. Its primary endpoint is clearly defined by assay, threshold, strains, and assessment times. The record also provides some adverse-event counts. These features allow readers to understand what the study set out to measure and which groups were included.

The record does not report numerical results for the primary immunogenicity endpoint. It therefore cannot establish from this record what percentage met the hSBA threshold, how precise those estimates were, or how the groups compared on that endpoint. The endpoint is an assay-based immune measure, not a direct measure of meningococcal disease occurrence. The record does not report disease-incidence results that would answer a clinical effectiveness question.

Nor do the listed safety counts establish that vaccination caused or prevented any particular adverse event. The study was open label and non-randomized, and the risk-condition groups are not interchangeable with healthy controls. The design is descriptive, and the registry record does not report a causal analysis or detailed adjustment strategy. The healthy group should not be interpreted as a randomized control arm.

The completed status indicates that the study is recorded as completed, not that all details needed to evaluate its findings are available in the registry record. Numerical endpoint estimates, confidence intervals, methods for missing observations, and a full statistical analysis plan are not reported there. The most defensible reading is therefore limited: the record specifies the intended immune-response assessment and reports selected safety counts, while leaving the magnitude and precision of the primary immune response unresolved.

13. Why This Trial Matters Statistically

This trial is statistically notable because it studies an immune-response endpoint in populations with conditions identified as reasons for increased meningococcal disease risk, alongside age-matched healthy controls. The endpoint uses a defined assay threshold and names the strains and assessment times, making the intended measurement interpretable. The study also records safety information across several risk and control categories.

At the same time, the non-randomized design is central to interpreting comparisons. The participant groups were defined by health status rather than assigned at random to different health conditions. Matching on age is mentioned, but the registry record does not describe its implementation or report other adjustment methods. Consequently, differences between groups may be associated with characteristics beyond the condition used to define each group. This matters even when the comparison is intended to be descriptive.

The record also illustrates why a clearly defined endpoint is not enough for statistical interpretation. Without its numerical percentage estimates and confidence intervals, readers cannot evaluate effect size or precision. Without details of multiplicity, missing-data handling, or analysis methods, it is difficult to assess how the endpoint was analyzed. The registry record does not report these details.

Finally, the safety counts must be interpreted in the context of the listed categories and without assuming causation. The record includes a combined CompDef + Asplenia category as well as separate categories, and the structure should not be collapsed into newly calculated totals. This study is useful for understanding the intended assessment and the limits of registry-level reporting, but the available record does not support a complete statistical evaluation of its primary findings.

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 important limitation for interpreting the primary question is that numerical immunogenicity results are not reported in the registry record. Although the endpoint and confidence-interval measure are specified, the record does not give percentages, interval limits, or numerical comparisons among the groups. This prevents assessment of the magnitude and precision of the primary outcome.

The design was non-randomized and open label. The healthy controls were age-matched and intended as descriptive controls, but the record does not report the matching procedure or detail how other group differences were addressed. Comparisons between participants with underlying risk conditions and healthy participants may therefore be confounded. The registry record does not report an adjusted analysis that would resolve this concern.

Important analysis details are also unavailable. The record does not report the full statistical plan, the method used to calculate confidence intervals, a multiplicity strategy, or the handling of missing or unevaluable assay results. The Full Analysis Set description is not complete enough in the registry record to establish every inclusion and exclusion rule. The record lists 0 analyses, and numerical primary endpoint findings are unavailable there.

For safety, the record gives counts and selected serious-event terms but does not report event attribution, a detailed account of ascertainment, or deaths. The categories include both separate risk-condition groups and a combined CompDef + Asplenia group; their relationship is not explained in enough detail to support additional calculations or direct comparisons. These limitations mean the registry record supports a description of the study design and selected reported counts, but not a full independent assessment of efficacy, safety causality, or statistical robustness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of Novartis Meningococcal B Vaccine When Administered to Immunocompromised Children and Adolescents Compared to Healthy Subjects. — NCT02141516.
• Registry record last updated 2017-02-15; status last verified 2016-07.
• Results first posted 2017-02-15.
• 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

NCT02141516 is recorded as a completed Phase IIIb, open-label, non-randomized, parallel-group study of rMenB+OMV NZ in children and adolescents from 2 to 17 years of age. It enrolled 239 participants and included groups with complement deficiency, asplenia or splenic dysfunction, and age-matched healthy controls. The vaccination schedule described in the endpoint information was two doses on Day 1 and Day 61.

The primary endpoint was the percentage with hSBA titers of at least 5 against the listed serogroup B strains at Day 1 and Day 91, with a 95% confidence interval specified. Numerical primary endpoint results are not reported in the registry record. Selected adverse-event counts and serious-event terms are reported, but event attribution and deaths are not reported in the registry record. Details of the statistical analysis, multiplicity handling, and missing-data methods are also not reported.