Duration of hSBA Response After a Primary Series of Bivalent rLP2086 Followed by a Booster Dose: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Duration of hSBA Response After a Primary Series of Bivalent rLP2086 Followed by a Booster Dose (NCT01543087), a registered phase 3 study. The primary outcome is Percentage of Participants in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations.

2. Clinical Question

The primary endpoint is an immunogenicity measure: it classifies participants according to whether their measured hSBA titer reached a strain-specific assay threshold. It is not a direct measure of meningococcal disease occurrence. The registry describes the intended assessments, but the primary outcome percentages and confidence intervals are not reported in the registry record.

3. Trial Design

This was a phase 3 study of bivalent rLP2086, with no masking reported. The registry record lists the study as completed and reports enrollment of 698. Its stated purpose was to assess immune-response persistence for approximately 48 months after a primary series, followed by a booster and assessment of immune response for 12 or 26 months after the booster.

The Stage 1 groups included one group receiving MCV4, Tdap, and saline on a 0-, 2-, and 6-month schedule, and groups receiving rLP2086 on different schedules: 0-, 1-, and 6-month; 0-, 2-, and 6-month; 0- and 6-month; 0- and 2-month; or 0- and 4-month. Stage 2 lists rLP2086 groups corresponding to the latter five schedules. The registry record does not state how participants were allocated to groups, so these groups should not be treated as a randomized, like-for-like comparison.

The primary endpoint described in the record is at Month 6, Visit 1 of study B1971033. Participants who had received bivalent rLP2086 in primary study B1971012 entered this study at Month 12, so they did not contribute Month 6 serology results. This enrollment timing matters when interpreting which participants and time points are represented in the endpoint. The registry record does not report further details of the study protocol or statistical analysis plan.

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: This study consisted of 2 stages: Stage 1 and Booster stage. Only participants from primary studies B1971010 and B1971012 who received bivalent rLP2086 in the primary study and completed Stage 1 in this study, were eligible to participate in the booster stage.

Stage 1 (48 Months)

Reasons for not completing this period:

Booster Stage (26 Months)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified intent-to-treat (mITT) population included participants who had at least 1 valid and determinate assay result in Stage 1 of Study B1971033. Here, 'Number analyzed' signifies number of participants with valid and determinate hSBA titers for the given strain.

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: Full analysis set included all participants enrolled in this study from primary studies B1971010, B1971012, and B1971015.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations, measured over Month 6 (Visit 1 of study B1971033).

The primary endpoint is the percentage of Stage 1 participants whose hSBA titer reached at least the lower limit of quantitation (LLOQ) for each of four primary Neisseria meningitidis serogroup B test strains at Month 6 after primary vaccinations. hSBA is a serum bactericidal assay using human complement. The LLOQ was 1:16 for PMB80 (A22), and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44).

This endpoint turns an assay measurement into a binary classification for each strain: the participant’s result is either at least the assay’s quantitation threshold or below it. Reporting a percentage makes the frequency of threshold attainment interpretable, while a confidence interval conveys uncertainty around that estimated percentage. The endpoint is used to describe immunogenicity, not to establish a clinical effect on disease. The registry record does not provide the observed percentages or their confidence intervals, and it does not report a clinical protection threshold.

For this measure, the modified intent-to-treat population included participants with at least one valid and determinate assay result in Stage 1 of study B1971033. The number analyzed for a particular strain refers to participants with valid and determinate hSBA titers for that strain. Accordingly, the analyzed count can depend on whether a usable result was available for the particular assay.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is a binary proportion for each assay strain. For a given participant and strain, the result is classified by whether the hSBA titer reached at least the LLOQ. The reported percentage would describe the fraction of analyzed participants meeting that criterion. Because the strain-specific thresholds are not identical, each strain’s proportion has its own interpretation and should be considered separately.

What does a confidence interval add?

A confidence interval expresses uncertainty around an estimated quantity. For a proportion, it gives a range of values compatible with the observed data under the interval’s statistical assumptions. A narrower interval generally indicates greater precision; a wider interval indicates less precision. The registry endpoint description specifies a two-sided 95% confidence interval, but does not report the actual interval estimates or the method used to calculate them. The calculation method should not be inferred from the confidence level alone.

Who is included in the endpoint analysis?

The defined modified intent-to-treat population includes participants with at least one valid and determinate assay result in Stage 1 of study B1971033. For each strain, the number analyzed is the number with a valid and determinate hSBA titer for that strain. This definition makes the usable assay result central to inclusion in the strain-specific calculation. The record does not report how many participants were analyzed for each strain or how missing or indeterminate results were handled beyond this population definition.

Why do the study groups not establish a direct treatment contrast?

The record lists multiple schedules and says the study is not a randomized comparison, with allocation not stated. A group contrast is most interpretable when the groups are comparable apart from the treatment or schedule being assessed. When allocation and comparability are not established, observed differences can reflect group composition or other factors as well as the schedule. The record does not describe an adjusted comparison that would address those concerns. The schedules should therefore be read as descriptions of study groups, not as evidence of a causal ranking.

What should be understood about planning illustrations?

A sample-size planning illustration based on an observed effect is a hypothetical calculation for a future study under stated assumptions; it is not observed power for the completed trial. The planning assumptions described for this record are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. For ordinary outcomes, the illustration is expressed as participants per arm; for time-to-event outcomes, it is expressed as a total number of events using the Schoenfeld method. These assumptions do not constitute the original trial’s design justification. That justification is not reported in the registry record.

What is not known about the analysis?

The registry record does not report the statistical analysis plan, the method for constructing the confidence intervals, or the handling of multiplicity across strains and other outcomes. It also does not report interim analyses. Without those details, the endpoint definition can be explained, but the exact inferential procedure and any prespecified hierarchy of analyses cannot be reconstructed. General statistical principles do not fill in those trial-specific omissions.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint involves four strains, with a percentage and confidence interval described for each. Assessing several outcomes can raise a multiplicity question: if many statistical claims are tested, the chance of at least one apparently notable finding can increase. The registry record does not report whether multiplicity adjustments were planned, whether the four strain results were treated as co-primary, or whether another testing hierarchy was used. It would be inappropriate to assume a correction or inferential strategy.

The record describes a modified intent-to-treat population based on having at least one valid and determinate assay result in Stage 1 of study B1971033. For a given strain, only participants with a valid and determinate titer are counted as analyzed. This describes the analysis population, but the registry record does not report the number of missing or indeterminate measurements, reasons for missingness, or any imputation method. The impact of incomplete assay data on the estimates therefore cannot be assessed from the record.

One timing issue is explicitly described: participants from primary study B1971012 entered at Month 12, and none had serology results at Month 6 in this study. Their absence from the Month 6 endpoint follows from entry timing and should not be interpreted as a negative assay result. The record does not report additional details about missing-data sensitivity analyses or how later follow-up measurements were analyzed.

These omissions limit what can be concluded about the statistical testing and robustness of results. The endpoint definition and population criteria are available, but the analysis plan and key missing-data details are not reported in the registry record.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: influenza like illness (1.9%), suicide attempt (1.7%), pyelonephritis (1.6%), depression (1.6%), meniscus injury (1.1%).

The safety entries list serious adverse events, other adverse events, and deaths by group. For Stage 1, the serious-event entries show zero participants at risk and zero affected in each listed group; deaths are also listed as zero in each group. For Stage 2, the serious-event entries show 1 of 59 affected in Group 2, 1 of 92 in Group 3, 2 of 64 in Group 4, 1 of 54 in Group 5, and 0 of 32 in Group 6. Deaths are listed as zero in each Stage 2 group. These are the recorded counts, not estimates of comparative risk.

The other-adverse-event entries include 4 affected among 70 at risk in Stage 1 Group 1; 0 among 101 in Group 2; 1 among 277 in Group 3; 0 among 116 in Group 4; 2 among 86 in Group 5; and 1 among 46 in Group 6. Stage 2 entries list 56 among 59, 90 among 92, 62 among 64, 53 among 54, and 31 among 32 for Groups 2 through 6, respectively. The registry record also lists top serious-event terms with percentages, including influenza like illness at 1.9%, suicide attempt at 1.7%, pyelonephritis at 1.6%, depression at 1.6%, and meniscus injury at 1.1%. The record does not give enough detail to establish how these terms relate to specific groups or exposure time, so they should not be compared as group-specific rates.

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

The study was designed to describe immune-response persistence after a primary bivalent rLP2086 series and immune response after a booster. Its primary endpoint uses the proportion of participants reaching a strain-specific hSBA assay threshold at Month 6. This is an immunogenicity outcome. It does not, by itself, measure clinical disease incidence or establish a clinical protection threshold.

The registry record does not report the primary endpoint percentages or confidence intervals. Consequently, it does not support a statement about the size or precision of the observed Month 6 responses. Although the study’s stated objectives include persistence and booster assessments, the aims and follow-up periods are not substitutes for the missing outcome results. Results for those later assessments are not reported in the registry record.

The different vaccination schedules provide context for the study groups, but the record identifies the comparison as nonrandomized and says allocation was not stated. That limits the interpretation of between-group differences. Even if numerical group results were available, they would not automatically establish that one schedule caused a better or worse outcome than another.

The safety listings describe affected participants and deaths in the registry’s group entries. They are useful as recorded counts, but do not alone establish comparative safety, explain causality, or account for differences in follow-up or exposure. The completion status and total enrollment likewise do not resolve these interpretation limits.

In short, the record establishes what the study intended to measure and gives some group-level safety counts. It does not provide the primary outcome results needed to characterize the observed immune responses. No conclusion about treatment benefit or lack of benefit follows from the endpoint description alone.

13. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an outcome result are not the same thing. The registry specifies a measurable immunogenicity endpoint, including the assay, four test strains, strain-specific LLOQ values, time point, and analysis-population definition. Those details allow readers to understand what a reported percentage would mean. Yet the registry record does not report the percentages or confidence intervals, so the endpoint description cannot answer how often participants reached the thresholds or how precise those estimates were.

It also highlights the importance of timing and population definitions. Participants entering from primary study B1971012 arrived at Month 12 and therefore did not contribute Month 6 serology. Recognizing this prevents a timing-related absence from being mistaken for a below-threshold result. Likewise, the strain-specific analyzed population depends on having a valid and determinate assay result for that strain.

The group schedules demonstrate another statistical distinction: listed groups are not necessarily valid comparative groups. The record says allocation was not stated and the study was not a randomized comparison. That makes causal interpretation of group differences uncertain, regardless of how appealing a numerical contrast might appear.

Finally, safety counts and planning illustrations answer different questions from the primary endpoint. Safety entries describe recorded events by group, while planning calculations illustrate assumptions for a possible future study. Neither supplies the missing primary immunogenicity estimates. Together, these features make the record a useful example of why study aims, analysis definitions, observed results, and causal conclusions must be kept separate.

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 principal limitation for interpreting the primary question is that the registry record does not report the observed percentages or 95% confidence intervals for the four-strain Month 6 endpoint. The record also does not report results for the stated persistence period or the post-booster follow-up. As a result, the planned immunogenicity questions cannot be answered from the reported outcome information.

The analysis population is defined, but strain-specific analyzed counts, missing-result counts, and details of missing-data handling are not reported in the registry record. The record explains that participants entering from primary study B1971012 did not have Month 6 serology in this study because they entered at Month 12. This means that the endpoint does not represent Month 6 observations from those entrants.

The study groups followed different schedules, and the registry notes that allocation was not stated and that the comparison was not randomized. Group differences therefore cannot be treated as direct causal effects. The statistical analysis plan, confidence-interval method, multiplicity approach, and interim-analysis details are also not reported in the registry record.

Safety information is presented as group-level counts and a list of serious-event terms with percentages, but the record does not provide the exposure or follow-up details needed for a comparative safety analysis. The record also does not supply enough context to determine how the listed serious-event terms map to individual groups. These limitations constrain interpretation even though enrollment, study completion, endpoint definitions, and some safety counts are recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Duration of hSBA Response After a Primary Series of Bivalent rLP2086 Followed by a Booster Dose — NCT01543087.
• Registry record last updated 2020-03-27; status last verified 2020-02.
• Results first posted 2020-03-27.
• 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

This completed phase 3 study assessed the persistence of hSBA responses after a primary bivalent rLP2086 series and immune response after a booster. The stated persistence period was approximately 48 months, with post-booster assessment for 12 or 26 months. The registry record reports enrollment of 698 and lists groups with different vaccination schedules.

The primary endpoint was the percentage of Stage 1 participants reaching at least the LLOQ for each of four primary strains at Month 6. Its analysis population required at least one valid and determinate assay result, with strain-specific analyzed counts based on valid results for that strain. Participants from primary study B1971012 entered at Month 12 and had no Month 6 serology in this study.

The primary outcome percentages and confidence intervals are not reported in the registry record. Allocation methods, the statistical analysis plan, multiplicity handling, and additional missing-data methods are also not reported. The safety entries list group-level event counts and deaths, but do not establish comparative safety.