Immunogenicity and Safety of Meningococcal Vaccine GSK 134612 Versus Mencevax™ ACWY in Healthy 18-25 Year Olds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety of Meningococcal Vaccine GSK 134612 Versus Mencevax™ ACWY in Healthy 18-25 Year Olds (NCT01154088), a randomized phase 3 study. The primary outcome is Number of Subjects With Vaccine Response for Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibodies.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, triple-masked, parallel study. Its stated purpose was to assess the immunogenicity and safety of one dose of GSK Biologicals’ meningococcal vaccine GSK 134612 compared with one dose of Mencevax ACWY in healthy subjects aged 18-25 years. It also aimed to compare the immunogenicity of two lots of the GSK vaccine. The record lists 1170 participants enrolled and gives the study status as completed.

The study began on 2010-08-27, and its primary completion date is listed as 2010-12-30. These registry dates describe the recorded study timeline; they do not, by themselves, provide information about follow-up duration for every outcome or when each participant was assessed. The primary outcome’s timeframe is At Month 1.

The interventions are listed as Mencevax ACWY and the investigational GSK 134612 meningococcal conjugate vaccine. Three groups appear in the adverse-event information: Nimenrix-A, Nimenrix-B and Mencevax. The primary-outcome description specifies that its analysis concerns Nimenrix-A and Mencevax. The arm descriptions are blank, so the record does not provide a complete account of each group’s assigned product, the lot-to-group mapping, or group-specific procedures.

Randomization indicates that assignment was planned to use chance, while triple masking indicates that the record describes masking at three levels. The identities of the masked parties and the practical masking procedures are not reported in the registry record. The record also does not report allocation concealment details, the randomization method, or a more detailed protocol description.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity measures were available. This primary outcome and the statistical analyses performed for this outcome concern the Nimenrix-A Group and Mencevax Group only.

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 Number of Subjects With Vaccine Response for Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibodies, measured over At Month 1.

The primary outcome counts participants who met the study’s definition of vaccine response for antibodies against meningococcal serogroups A, C, W-135 and Y. The measurement used a serum bactericidal assay with rabbit complement, abbreviated rSBA in the outcome description, and the analysis was performed with the GSK rSBA assay. The assessment time was At Month 1.

The response definition accounts for participants’ initial serostatus. For participants who were initially seronegative, response required an antibody titer at least 1:32. For participants who were initially seropositive, response required a titer at least fourfold the pre-vaccination titer. This makes the endpoint a threshold-based, participant-level outcome rather than a comparison of average titers alone. The endpoint title refers to antibodies against all four serogroups; the record does not provide the response counts for each group or serogroup.

In general, an antibody response endpoint can describe whether participants reached a prespecified laboratory threshold after vaccination. It is not the same as measuring the occurrence of meningococcal disease, and an antibody response alone should not be presented as a direct count of illnesses prevented. The registry record does not report clinical disease outcomes or a numerical primary-outcome result, so the extent of the measured response and the precision of any comparison cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: a participant either meets the specified vaccine-response definition or does not. The registry describes the outcome as a count of participants, assessed at Month 1. Because response is defined using antibody titer thresholds that depend on initial serostatus, the underlying laboratory measurements are converted into a response classification. This kind of endpoint can be summarized as a count and, when an appropriate denominator is available, as a proportion. The registry record does not report the primary response counts or denominators by group.

What does randomization contribute?

In general, random assignment is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline characteristics. This supports a causal interpretation of a comparison when assignment is implemented as planned and the analysis appropriately follows the randomized groups. Randomization does not ensure that groups will be exactly alike, and it does not remove the need to report how many participants were analyzed or how missing observations were handled. The record identifies the study as randomized but does not report the randomization sequence method or allocation concealment details.

What does masking mean for interpretation?

The record characterizes the study as triple-masked. In general, masking is intended to reduce the chance that knowledge of assigned treatment influences participant reports, clinical assessments, or analytic decisions. The exact people or roles who were masked, and the procedures used to preserve masking, are not reported in the registry record. The label alone therefore does not establish how masking operated in practice or whether it remained intact.

How should a threshold endpoint be understood?

A threshold endpoint reduces a laboratory measurement to a yes-or-no classification using a stated rule. Here, the rule differs according to whether a participant was initially seronegative or seropositive. This approach makes the response definition clinically and scientifically interpretable as a prespecified benchmark, but it also means the count depends on the chosen thresholds and baseline classification. In general, participants close to a threshold can be classified differently from those far from it even when their underlying titers are similar. The registry record states the response rule but does not provide individual titers or distributions that would allow examination of such patterns.

What would an effect estimate and interval add?

For a binary endpoint, a comparison may be reported using group-specific response proportions and a measure of the difference or relative contrast between groups. These measures answer different questions and should be accompanied by uncertainty intervals. In general, a confidence interval communicates the precision of an estimated effect under the chosen statistical model; wider intervals indicate greater uncertainty, while narrower intervals indicate greater precision. A p-value, when reported, addresses compatibility of the data with a specified null model and is not a measure of effect size or clinical importance. The registry record does not report an effect estimate, confidence interval, or p-value for the primary outcome, so none can be interpreted.

What does the analysis population indicate?

The primary-outcome description states that analysis was performed on the According-To-Protocol cohort for immunogenicity. It characterizes this cohort as including evaluable subjects for whom immunogenicity measures were available. In general, an according-to-protocol analysis focuses on participants meeting specified study requirements and with outcome measurements available. It may therefore differ from an analysis that retains participants according to randomized assignment regardless of protocol adherence or missing outcomes. The registry record does not report the cohort’s inclusion and exclusion rules in detail, its size, or a separate intention-to-treat analysis.

The distinction between analysis populations matters because removing participants after randomization can affect comparability if the reasons for exclusion are related to assigned treatment, response, or prognosis. This is a general methodological concern, not evidence that such bias occurred in this study. The record does not report reasons for exclusions, missing primary-outcome observations, or sensitivity analyses, so their influence cannot be assessed.

How should planning illustrations be read?

Any sample-size figures associated with planning are illustrations based on the observed effect, not evidence of the trial’s original design justification and not observed power. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. The record does not report the trial’s own sample-size justification or protocol assumptions. Because the primary result is not reported, the planning illustration cannot be used to reconstruct the result or establish whether the trial was adequately planned. In general, power calculations are design tools based on assumptions, not a measure of the probability that a completed study’s finding is true.

Over-dispersion is a general issue for count outcomes when variability exceeds what a simple model assumes. It can make model-based uncertainty too small if the extra variability is ignored. The primary outcome is defined as a participant count, but the registry record does not identify an over-dispersion model or provide a model specification. It would be inappropriate to assume that a particular model or adjustment was used.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and 8 analyses. Several listed outcomes concern antibody titers, threshold-based antibody status, vaccine response, and solicited symptoms. Considering many outcomes or comparisons can raise a multiplicity issue: in general, the chance of at least one apparently notable result can increase when many statistical tests are conducted. Whether and how that issue is addressed depends on the analysis plan, including the designation of primary and secondary hypotheses and any adjustment or hierarchy.

The record identifies a primary outcome and describes the primary analysis population and comparison, but it does not report a statistical plan for controlling multiplicity, a testing hierarchy, or whether secondary outcomes were adjusted. It is therefore not possible to determine from the registry record how multiplicity was handled. This is not evidence that no adjustment was performed; the approach is simply not reported in the registry record.

The primary analysis used an According-To-Protocol cohort for immunogenicity, defined as evaluable subjects with immunogenicity measures available. The record does not report how many participants had missing primary measurements, why any measurements were unavailable, or how missing data were handled. It also does not give a detailed definition of evaluability or report sensitivity analyses under alternative missing-data assumptions.

In general, missing outcome data can affect an estimate if the probability of having an observed measurement is related to response or treatment group. An analysis restricted to participants with available measurements may be informative, but its interpretation depends on the reasons for missingness and the analysis assumptions. The registry record does not provide enough detail to assess those conditions. It also does not report an intention-to-treat result for the primary outcome, so comparisons between analysis populations cannot be made.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: blighted ovum (0.3%).

The adverse-event information lists three groups: Nimenrix-A, Nimenrix-B and Mencevax. For serious adverse events, the recorded at-risk counts are 390 in each group; the corresponding affected counts are 0, 1 and 0, respectively. No deaths are listed in any of the three groups. These are counts as recorded, not estimates of comparative risk adjusted for follow-up or other factors. The registry record does not report additional detail on event timing, duration, severity beyond the serious-event classification, or participant-level clinical context.

The record also lists other adverse-event affected counts of 274 for Nimenrix-A, 271 for Nimenrix-B and 237 for Mencevax, with 390 at risk in each group. These are distinct from the serious adverse-event counts and should not be read as serious events. The record gives “Blighted ovum” as a top serious term, with 0.3%, but does not identify which group that term belongs to or provide further case-level context. The percentages and counts should be interpreted as registry safety descriptions, not as a complete account of every event or a basis for causal conclusions.

In general, adverse-event comparisons depend on definitions, observation periods, and the completeness of reporting. Those details are not fully reported in the registry record. The listed figures alone do not establish whether one group had a meaningfully different safety profile.

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

The record establishes that a randomized, triple-masked, parallel Phase 3 study was conducted to evaluate the immunogenicity and safety of one dose of an investigational meningococcal vaccine compared with one dose of Mencevax ACWY in healthy subjects aged 18-25 years. It also states that the study aimed to compare the immunogenicity of two investigational-vaccine lots. The primary endpoint was a defined antibody response at Month 1, and the record specifies how the response threshold depended on initial serostatus.

Those details explain the research question and how the primary outcome was defined, but they do not provide the primary comparative result. Arm-specific response counts, denominators, effect estimates, confidence intervals and test results are not reported in the registry record. It is therefore not possible to say from this record which group had more participants meeting the response definition, how large any difference was, or how precisely it was estimated. The absence of a reported result should not be interpreted as evidence of no difference.

The antibody endpoint is a laboratory outcome. In general, meeting an antibody threshold is not equivalent to documenting protection against clinical disease. The registry record does not report a clinical meningococcal disease endpoint, so the primary outcome cannot be translated into a count of illnesses prevented or a direct estimate of clinical benefit.

The adverse-event information provides recorded counts for serious and other events, and it lists no deaths in the groups shown. It does not supply enough detail to determine causality, assess every safety dimension, or draw a comparative safety conclusion. The serious-event term reported with a percentage is not linked to a particular group in the record.

Overall, the record supports a description of the study’s design, intended comparisons, endpoint definition, analysis population and selected safety counts. It does not contain the numerical primary efficacy or immunogenicity results needed to judge the observed response or its uncertainty. General interpretation should remain limited to these recorded elements.

13. Why This Trial Matters Statistically

This trial is statistically relevant because its primary endpoint illustrates how a laboratory measurement can be converted into a participant-level binary outcome. The vaccine-response definition uses different thresholds according to initial serostatus, making the classification rule central to interpreting any group comparison. Understanding that rule is necessary before a response count can be given meaning.

The record also illustrates the distinction between a randomized study design and a reported statistical result. Randomization, masking and a parallel structure describe important features of the planned comparison. They do not, on their own, show the size of an outcome difference or its uncertainty. For that, readers need arm-specific results, analysis denominators, an estimate of the comparison and an interval or other account of precision. Those primary results are not reported in the registry record.

The stated analysis population matters as well. An according-to-protocol immunogenicity cohort is described as including evaluable participants with available measurements. In general, analysis-population definitions affect which participants contribute to an estimate and how that estimate should be interpreted. The missing detail on cohort size, exclusions and outcome availability prevents assessment of how the analyzed group relates to the randomized study population.

Finally, the study addressed both immunogenicity and safety, and the record includes several types of outcomes. This makes clear why primary and secondary outcomes, analysis populations, multiplicity procedures and missing-data handling should be transparently reported. The registry description identifies the primary question but does not supply enough statistical results or analysis detail to assess those issues fully. Its value for statistical interpretation lies in the design and endpoint information it documents, while its limits are defined by the results and methods not reported.

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 this trial from the registry record is that the primary outcome is described without arm-specific response results. Counts, denominators, comparative estimates and uncertainty intervals are not reported. The record therefore does not support a numerical assessment of the primary immunogenicity comparison.

Other details relevant to interpretation are also absent. The arm descriptions are blank, and the record does not provide the exact mapping of the investigational vaccine lots to group labels or a complete account of assignment procedures. It identifies the primary comparison as Nimenrix-A versus Mencevax, but does not report group-specific primary-analysis sizes or participant flow. The according-to-protocol cohort is described in general terms, without its size, detailed eligibility rules, exclusions or missing-measurement information.

The registry record does not report a statistical analysis plan, the trial’s sample-size justification, multiplicity procedures, a detailed missing-data approach, or sensitivity analyses. These omissions limit assessment of whether the reported analysis strategy was prespecified and how robust a result might be to alternative assumptions. They do not establish that these methods were absent from the study; they are not reported in the registry record.

Safety interpretation is limited by the absence of detailed event descriptions, observation-period information and group attribution for the listed serious term. The record provides selected counts but does not give sufficient case-level context or a comprehensive account of safety analyses. It also does not report clinical disease outcomes. Accordingly, the available information supports a description of study design, endpoint definition and recorded safety counts, but not a complete assessment of comparative efficacy, immunogenicity or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety of Meningococcal Vaccine GSK 134612 Versus Mencevax™ ACWY in Healthy 18-25 Year Olds — NCT01154088.
• Registry record last updated 2018-11-26; status last verified 2018-05.
• Results first posted 2018-11-26.
• 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

NCT01154088 is a completed Phase 3, randomized, triple-masked, parallel study of one dose of GSK Biologicals’ meningococcal vaccine GSK 134612 and one dose of Mencevax ACWY in healthy subjects aged 18-25 years. The record lists 1170 enrolled participants and states that the study also compared the immunogenicity of two investigational-vaccine lots.

The primary outcome was the number of participants meeting a serogroup-specific antibody-response definition at Month 1, analyzed in the According-To-Protocol cohort for immunogenicity. The primary comparison is identified as Nimenrix-A versus Mencevax. Arm-specific primary results and their precision are not reported in the registry record. Safety information includes serious and other adverse-event counts for Nimenrix-A, Nimenrix-B and Mencevax, with no deaths listed in those groups.

The study began on 2010-08-27, with primary completion listed as 2010-12-30. The record does not report a detailed statistical plan, sample-size justification, multiplicity procedure, or handling of missing primary-outcome data.