A Phase 3b Study to Assess the Safety of Novartis Meningococcal B Recombinant Vaccine When Administered in Healthy At-risk Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 3b Study to Assess the Safety of Novartis Meningococcal B Recombinant Vaccine When Administered in Healthy At-risk Adults (NCT01478347), a non-randomized phase 3 study. The primary outcome is Number of Subjects Reporting Unsolicited Adverse Events, Following Vaccination With Two Injections of rMenB+OMV NZ Vaccine Between Day 1 Through Day 91..

2. Clinical Question

3. Trial Design

The registry record describes a Phase 3b, single-center, open-label study of rMenB+OMV NZ in healthy adults considered at risk because of occupational exposure to meningococcal cultures. The listed phase is PHASE3, and the official title identifies the study as Phase 3b. Enrollment was 18, and the study status is completed.

The design is listed as non-randomized, unmasked, and single-group. Participants received the vaccine rather than being assigned by chance to separate treatment groups. With no concurrent control group, the record can describe adverse events observed among vaccinated participants, but it cannot estimate a randomized between-group contrast. Open-label means the study was not masked; the registry record does not report further details about who knew participants' treatment status.

The intervention is rMenB+OMV NZ, described as recombinant meningococcal B vaccine with OMV NZ. The schedule was two injections, with the official title specifying a 0, 2-month schedule. The enrolled population was described as healthy adults aged at least 18 and at most 65 with routine occupational exposure to N. Meningitidis cultures. The study also planned a second part in which additional blood samples from high-responding vaccinated participants would be collected to generate a control serum panel for human serum bactericidal assay tests. The posted primary safety outcome concerns the first part.

The registry lists a start in 2013-05 and primary completion in 2014-03. The record does not report the rationale for choosing the enrollment target, details of recruitment, or how many participants entered the planned second part. Those details should not be inferred from the study title or the posted safety counts.

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 enrolled subjects participated in the study.

Visit 1-Visit 3 (Day 0-91) - Part I

Reasons for not completing this period:

Visit 4-Visit 7 (Day 151-331) - Part II

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: This analysis was done on the safety set population i.e all subjects in the exposed set with unsolicited adverse event data for part one of the study.

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: Healthy adults (≥18 to ≤65 years), at high risk for meningococcal B disease due to routine occupational exposure to N. Meningitidis cultures, were administered two injections of rMenB + OMV NZ vaccine, 2 months apart in part I (Visit 1-Visit 3). In part II (Visit 4-Visit 7), subjects were re-enrolled for optional blood draws and safety follow-up.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Reporting Unsolicited Adverse Events, Following Vaccination With Two Injections of rMenB+OMV NZ Vaccine Between Day 1 Through Day 91., measured over Day 1 to day 91.

The primary outcome is the number of subjects reporting unsolicited adverse events following vaccination with two injections of rMenB+OMV NZ, during Day 1 to day 91. The outcome description specifies serious adverse events, medically attended adverse events, and adverse events leading to premature withdrawal. It also says the analysis used the safety set: exposed participants with unsolicited adverse-event data for part one of the study.

In general, a safety endpoint records harms or other untoward events observed during a defined follow-up period. Counting participants with an event is a descriptive way to show how many people were affected, rather than how many separate episodes occurred. This distinction matters because one participant can experience more than one event; the posted participant count does not by itself convey event frequency, duration, severity beyond the reported categories, or clinical course.

The outcome is relevant to a safety-focused study because it describes events reported after vaccination in the population under study. However, a count in a single group does not establish that vaccination caused an event. Without a comparator, background events and events attributable to other circumstances cannot be separated using this outcome alone. The registry record does not report further operational definitions for unsolicited events, medically attended events, or premature withdrawal.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a safety analysis that counts participants with an event summarizes how many people experienced at least one event in a specified category during a defined observation period. This is different from counting every event episode. If one person has repeated events, a participant-level count still includes that person once in the relevant category. The registry outcome is phrased as a number of subjects, and the posted results give participant counts at risk and affected.

The time window matters because an event outside the defined follow-up does not necessarily contribute to the stated endpoint. The record gives the primary safety timeframe as Day 1 to day 91. It does not report detailed rules for assigning onset dates, handling events that began before vaccination, or deciding whether events after the follow-up window were included. Such rules can affect which observations enter a safety summary, so they should not be assumed.

In general, a denominator identifies the group in which the event count was assessed. The registry defines the safety set as all subjects in the exposed set with unsolicited adverse-event data for part one of the study. For serious and other adverse events, the posted results give 18 participants at risk. A clear denominator makes the scope of the count easier to understand, but it does not resolve questions about missing data or follow-up completeness. Those procedures are not reported in the registry record.

In general, confidence intervals express uncertainty around an estimate and show a range of values compatible with the observed data under the method's assumptions. A participant count alone does not provide that precision information. No confidence interval is reported for the posted event counts. It would therefore be inappropriate to treat the counts as precise estimates of the event frequency in all adults at occupational risk, or to infer an unreported interval.

In general, a comparative analysis needs a contrast that corresponds to the study design. Random allocation can make groups more comparable on average, while a single-group study has no randomized group to serve as a reference. Here, the design is listed as non-randomized and single-group. As a result, the posted adverse-event counts describe the vaccinated group only. They do not provide a risk difference, relative risk, or other between-group measure. No comparative analysis is reported in the registry record.

The record's planning illustration assumptions describe a hypothetical two-arm design, with equal allocation, a two-sided significance level of 0.05, and a normal approximation. They describe an effect to detect as a stated fraction of the observed effect. These are planning assumptions, not features that turn the single-group trial into a two-arm comparison. Any sample-size illustration based on those assumptions is hypothetical and is not observed power. The registry record does not report the study's own sample-size justification or say that those assumptions were used to choose its enrollment.

In general, over-dispersion is a concern when count data vary more than a chosen statistical model expects; a model that understates that variation can give overly narrow uncertainty estimates. That concept is not a reported method for this safety outcome. The record identifies a binary outcome type, meaning the relevant summary is participants with an event, but does not report a model-based analysis, a dispersion estimate, or an adjusted effect estimate.

In general, open-label status can matter for adverse-event collection because participants and investigators know the treatment received, and that knowledge may influence recognition or reporting. This is a methodological consideration, not evidence that reporting was biased in this study. The registry record does not describe masking procedures, event adjudication, or independent review beyond listing the study as having no masking.

The posted result is therefore best read as a descriptive safety summary: 0 participants with serious adverse events and 2 with other adverse events among 18 at risk in each category. The record does not report inferential estimates that would support a broader quantitative comparison. The counts remain useful as a record of what was observed in this study, but their interpretation is bounded by the single-group design, the size of the enrolled group, and the reporting details available.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures, but the record does not report a multiplicity strategy or explain whether any outcome was designated as primary for formal hypothesis testing beyond the named safety outcome. Multiplicity procedures are generally used when several statistical tests are planned, because considering many results can increase the chance of a chance finding. No adjustment for multiple testing is reported in the registry record. The posted participant counts should therefore be read as descriptive results, not as a set of adjusted hypothesis tests.

The record describes the safety set as exposed participants with unsolicited adverse-event data for part one. It does not report how missing event information was handled, whether participants with incomplete follow-up were included for all of Day 1 to day 91, or whether any imputation was used. It also does not report how withdrawals were handled in the analysis beyond identifying adverse events leading to premature withdrawal as part of the outcome description. Missingness should not be assumed to mean that no event occurred.

The record does not report a detailed statistical analysis plan, prespecified interim analyses, or rules for handling multiple event categories. The sample-size justification is also not reported in the registry record. These omissions limit assessment of how the endpoint definitions and analyses were chosen. They do not change the basic interpretation of the posted safety counts, but they leave uncertainty about planned analyses and the treatment of incomplete information.

Because the study is single-group, there is no control-group comparison to adjust or test. The reported counts characterize participants with available unsolicited adverse-event data in the defined safety set; they do not establish a causal effect or quantify a comparative difference.

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 non-serious adverse event terms

The registry reports 0 participants with serious adverse events among 18 at risk in the rMenB+OMV NZ group. It reports 2 participants with other adverse events among 18 at risk. These are participant counts, not counts of all event episodes. The figures refer to the safety outcome period from Day 1 to day 91.

The serious adverse-event count is not the same as a statement that serious events are impossible or that the risk is zero outside this study. It records no affected participants in this group during the reported period. The other adverse-event count is recorded separately; the registry record does not give event terms for those participants in the serious-event listing.

The registry record does not report a death count. It also does not list top serious-event terms. Those absences should not be converted into additional conclusions beyond what is recorded. The result does not give separate counts for medically attended adverse events or adverse events leading to premature withdrawal.

In general, adverse-event counts describe observations and do not alone establish causation. The single-group design has no randomized comparator, and the posted counts do not distinguish events caused by vaccination from events arising for other reasons.

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

The result means that, in this study's safety set, the registry records no participants with serious adverse events and 2 participants with other adverse events, with 18 at risk in each category. The observations apply to the enrolled group of healthy adults described as at high occupational risk for meningococcal B disease, and to the stated follow-up from Day 1 to day 91. They are a description of the reported data rather than a comparative estimate.

The result does not mean that serious adverse events cannot occur. A study of 18 participants can describe what was observed among those participants, but a zero count does not rule out events in a larger population or during a different period. No confidence interval or other precision measure is reported in the registry record, so the uncertainty around the observed counts is not quantified there.

The result also does not establish that vaccination caused the events recorded, or that it prevented events. A single-group study has no concurrent comparison group, and the design is not randomized. Events that occur after vaccination may have other explanations; the counts alone cannot separate those possibilities. Nor do these results compare rMenB+OMV NZ with another vaccine or with no vaccination.

The record focuses on safety and does not provide an efficacy conclusion. Its brief summary also describes collection of additional blood samples from high-responding vaccinated participants for a control serum panel used in human serum bactericidal assay tests. That planned laboratory activity does not change the interpretation of the posted adverse-event counts.

These findings are therefore a limited description of reported events in a small, specific occupationally exposed group during the recorded follow-up. They can be read as part of the study record, but they do not settle broader questions about comparative safety, uncommon events, or outcomes in populations unlike those enrolled.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of what a single-group safety study can and cannot show. The registry record gives a defined population, an intervention schedule, a follow-up window, a safety-set description, and participant counts for serious and other adverse events. Those details allow readers to understand the scope of the observations rather than treating an event count as a result without context.

At the same time, the design places clear limits on inference. Because there is no randomized comparator, the analysis is descriptive rather than a controlled estimate of relative safety. The counts answer how many participants in the recorded group had events; they do not answer how those counts would differ under another treatment or no vaccination. This distinction is central when interpreting safety evidence from a single group.

The small enrollment also makes it important to distinguish the observed count from a general estimate. No serious adverse events were recorded among the 18 at risk, but that observation cannot establish the absence of serious events beyond the study. The record does not report an uncertainty interval, a sample-size justification, or a formal comparative analysis, so the precision and design rationale cannot be assessed from the registry record.

The study also illustrates why safety summaries need explicit definitions. The endpoint description names serious events, medically attended events, and events leading to premature withdrawal, while the posted result gives serious and other event counts. The record does not provide separate counts for each named category or the detailed rules used to classify events. Clear reporting of those distinctions helps readers judge what a count represents and what remains unknown.

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 interpretation is the absence of a comparator. The study is listed as non-randomized and single-group, so adverse-event counts cannot be contrasted with counts under another treatment or no vaccination. Events observed after vaccination cannot be attributed to vaccination on these data alone.

Enrollment was 18. This provides a limited set of observations for assessing safety, particularly for events that may not occur often. The registry record does not report a confidence interval or another measure of precision, and it does not report the rationale for the enrollment target. The counts should not be treated as precise estimates for all adults at occupational risk.

The study was open-label, with no masking listed. In general, knowledge of treatment can influence how events are noticed or reported; the record does not establish that this occurred. It also does not report detailed event ascertainment procedures, adjudication methods, or rules for classifying events.

The primary outcome description refers to serious adverse events, medically attended adverse events, and adverse events leading to premature withdrawal. The posted results give 0 serious events and 2 other adverse events, but do not report separate counts for the other named categories. The death count is not reported in the registry record. No top serious-event terms are listed.

Finally, the record does not report handling of missing event data, follow-up completeness, or an analysis plan in enough detail to assess those issues. These reporting limits constrain interpretation but do not justify assuming that unreported categories had no events or that all participants had complete follow-up.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 3b Study to Assess the Safety of Novartis Meningococcal B Recombinant Vaccine When Administered in Healthy At-risk Adults — NCT01478347.
• Registry record last updated 2015-03-27; status last verified 2015-03.
• Results first posted 2015-03-06.
• 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

NCT01478347 is a completed, Phase 3b, single-center, open-label, non-randomized, single-group study sponsored by Novartis Vaccines. The registry lists enrollment of 18 and an intervention of recombinant meningococcal B plus OMV NZ vaccine. Healthy adults aged at least 18 and at most 65 with routine occupational exposure to N. Meningitidis cultures received two injections on a 0, 2-month schedule.

The primary safety outcome covers Day 1 to day 91. The registry reports 0 participants with serious adverse events and 2 with other adverse events, with 18 at risk in each category. It does not report a death count or separate results for medically attended events and events leading to premature withdrawal. As a single-group study, it provides descriptive safety counts rather than a randomized comparison.