Immunogenicity and Safety Study of GSK Biologicals' Meningococcal Vaccine GSK 134612 Versus Menactra® in Healthy Adolescents/Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety Study of GSK Biologicals' Meningococcal Vaccine GSK 134612 Versus Menactra® in Healthy Adolescents/Adults (NCT01165242), a randomized phase 2 study. The primary outcome is Number of Subjects With Vaccine Response to Serum Bactericidal Assay Using Human Complement Against Neisseria Meningitidis Serogroup A, C, W-135 and Y (hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY) Antibodies.

2. Clinical Question

In statistical terms, the study asked whether the measured antibody responses after vaccination differed across the two GSK 134612 lots and Menactra®. It also included safety outcomes, such as solicited symptoms, unsolicited adverse events, and new-onset chronic illness. Those additional outcomes provide a broader description of what was recorded during follow-up, but the endpoint definitions and response results are not all fully detailed in the available registry information.

3. Trial Design

The registry classifies NCT01165242 as a completed phase 2 study with randomized allocation, quadruple masking, and a parallel-group model. Its official title describes one dose of GSK Biologicals’ GSK 134612, using blinded lots, versus one dose of Menactra® in healthy subjects aged 10-25 years. The brief summary calls the study observer-blind, while the design information lists quadruple masking. The exact roles covered by the registry’s masking classification are not reported in the registry record.

The three arm descriptions assign participants to GSK 134612 Lot A, GSK 134612 Lot B, or Menactra®. This structure makes it possible to assess both the intended vaccine comparison and the consistency of immunogenicity between the two GSK 134612 lots. The overall enrollment was 1013. The registry record does not state how many participants were assigned to each group in the primary analysis population, or how many contributed evaluable results to each endpoint.

The study start date was 2010-08-19, and primary completion was 2011-02-25. The listed primary endpoint was measured one month after vaccination. The record describes the study as completed, but does not provide a detailed account of visit schedules, duration of safety follow-up, or procedures for handling participants who did not complete follow-up.

The registry lists immunogenicity and safety as the study’s aims. Secondary outcomes include antibody titers and the number of participants above a cutoff for each of the four serogroups, vaccine response for those antibodies, solicited local and general symptoms, unsolicited adverse events, and new-onset chronic illness. These are outcome categories rather than a complete account of the analysis plan: the registry record does not report all outcome-specific analysis details or a hierarchy among the secondary outcomes.

Although the study was randomized and masked, those design features do not by themselves establish how the outcomes compared. Interpreting a randomized trial’s findings requires the observed results, the population included in each analysis, and the statistical methods used. For the primary endpoint, the registry record supplies the response definition and analysis-cohort description but no response counts or comparison estimates.

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: Out of the 1013 subjects enrolled in this study, 2 were assigned subject numbers but received no vaccination and were hence excluded from the study start.

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 who had received the study vaccine dose and for whom assay results were available for antibodies against at least one study vaccine antigen component for the blood sample taken one month after vaccination.

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 to Serum Bactericidal Assay Using Human Complement Against Neisseria Meningitidis Serogroup A, C, W-135 and Y (hSBA-MenA, hSBA-MenC, hSBA-MenW-135 and hSBA-MenY) Antibodies, measured over One month after vaccination (Month 1).

The primary endpoint counted participants with a vaccine response to hSBA antibodies against meningococcal serogroups A, C, W-135, and Y one month after vaccination. hSBA is the assay named in the registry: a serum bactericidal assay using human complement. The endpoint therefore represents a threshold-based antibody response rather than a continuous change in antibody titer.

The response rule accounted for baseline status. For participants initially seronegative, defined as a hSBA titer below 1:4, response meant reaching a post-vaccination titer of at least 1:8. For participants initially seropositive, defined as a baseline titer of at least 1:4, response meant reaching a post-vaccination titer at least 4-fold the pre-vaccination titer. These criteria distinguish the threshold for participants with no detectable baseline response from the relative increase required for participants who already had measurable antibody.

Using a defined threshold gives a clinically interpretable count of participants who meet the study’s response criterion. It also simplifies comparison across groups, although the count does not describe the full distribution of antibody titers. The registry separately lists antibody titers and participants above cutoff as secondary outcomes, indicating that the study contemplated additional descriptions of immunogenicity. The endpoint’s response counts, group-specific estimates, and uncertainty are not reported in the registry record, so the magnitude and precision of any group differences cannot be assessed from the available primary-endpoint information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain what the recorded design and endpoint can address, while keeping separate general principles from methods actually documented for this trial. The registry identifies randomization, masking, a parallel-group model, a Month 1 response endpoint, and an According-to-Protocol immunogenicity cohort. It does not report a full statistical analysis plan, so general explanations should not be mistaken for procedures known to have been used.

What does randomization contribute?

In general, random allocation is intended to make treatment groups comparable, on average, with respect to factors that could affect outcomes. It supports a fairer comparison than allowing participants or investigators to choose the group. Randomization does not guarantee identical groups in a particular trial, especially for characteristics not reported, and it does not remove the need to describe which participants contributed to each analysis. The registry does not provide allocation methods, concealment details, or group counts for the primary immunogenicity analysis.

What does masking contribute?

In general, masking can reduce the influence of expectations on care, symptom reporting, outcome assessment, and analysis. The registry lists quadruple masking and separately describes the study as observer-blind. It does not explain which people were masked or how masking was maintained. For laboratory antibody measurements, masking may help limit expectation-driven handling or interpretation, but the record does not describe assay blinding procedures. These are general considerations, not confirmed details of the trial’s conduct.

How should a threshold-based endpoint be understood?

The primary outcome classifies each evaluable participant according to whether the prespecified response rule was met. That creates a binary outcome: response or no response under the stated definition. The rule differs according to initial antibody status, with a post-vaccination threshold for initially seronegative participants and a fold-rise requirement for initially seropositive participants. In general, threshold outcomes are straightforward to communicate as counts or proportions, but they discard information about how far a participant’s titer lies above or below the threshold. The registry also lists antibody titers as a secondary outcome, which can retain more of the measured scale.

Why does the analysis population matter?

The registry says the primary immunogenicity analysis used an According-to-Protocol cohort of evaluable participants who received the vaccine and had assay results for at least one antigen component. In general, restricting analysis to participants with evaluable measurements can make the endpoint easier to calculate, but it may affect interpretation if inclusion depends on events related to treatment or outcome. A complete appraisal would need the number randomized, the number included for each antigen, exclusions and reasons, and a clear account of missing measurements. Those details are not reported in the registry record. The truncated population description also prevents a fuller account of its criteria.

What would an estimate and confidence interval tell a reader?

In general, a group contrast summarizes the difference between outcomes under the chosen statistical scale, while a confidence interval describes the uncertainty around that estimate under the method’s assumptions. A narrow interval indicates greater precision than a wide interval, but neither the estimate nor its interval can be recovered without the outcome data and analysis details. The registry record does not report a primary comparison estimate or confidence interval. It also lists zero analysis entries, so no specific model, adjustment, or inferential procedure for the endpoint is documented in the record.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variation is greater than a statistical model expects. If a model assumes less variation than the data contain, standard errors can be too small and uncertainty can appear understated. This concept is relevant to some count-data methods, but the primary endpoint is recorded as a count of participants meeting a response definition, and no model or dispersion parameter is reported. There is no evidence in the registry record that an over-dispersion adjustment was used or needed for this endpoint.

How should planning illustrations be read?

In general, sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. The posted planning illustration is described as based on an observed effect, with 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. These are planning assumptions, not the trial’s documented original design. The registry record does not report the trial’s own sample-size justification. Planning calculations are not observed power and do not reveal whether the trial achieved a particular result.

The record also does not report interim analyses, a multiplicity adjustment, or the detailed approach to missing data. Their absence from the registry information should be understood as missing documentation, not evidence that a particular procedure was or was not conducted.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint concerns vaccine response across hSBA antibodies for serogroups A, C, W-135, and Y. Secondary outcomes also include antibody titers, the number of participants above a cutoff, and vaccine response across those serogroups, along with several safety outcomes. The study’s stated purpose includes comparing two GSK 134612 lots and comparing GSK 134612 with Menactra®. This creates multiple potential outcomes and comparisons. In general, when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity procedure, a hierarchy of hypotheses, or which comparisons were designated confirmatory.

The primary endpoint description gives the response definition and a Month 1 timeframe, but no group-specific counts or inferential results. The record notes that the primary outcome has several categories or time points and is not reduced to one comparison. Therefore, there is no single primary contrast available from the record to interpret, and no basis for reconstructing adjusted or unadjusted significance findings. The record lists no analysis entries.

For the immunogenicity population, the registry names an According-to-Protocol cohort consisting of evaluable participants who received the study vaccine and had assay results for antibodies against at least one vaccine antigen component. The description ends mid-sentence, so the complete analysis-population criteria are not available. The record does not report a full randomized-population analysis or explain whether other analysis populations were used.

Missing assay results and exclusions can affect the population contributing to a response estimate. In general, analysis of available measurements may be biased if the likelihood of having a measurement is related to treatment or the outcome. The registry does not report the extent or reasons for missing primary endpoint data, methods for addressing missing data, or sensitivity analyses. These omissions limit assessment of the robustness and generalizability of any immunogenicity comparison.

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: appendicitis (0.6%), pneumonia (0.6%), asthma (0.3%), hypoxia (0.3%), influenza (0.3%).

The registry lists serious adverse event counts for three groups. The Nimenrix Lot A Group had 1 participant affected among 337 at risk; the Nimenrix Lot B Group had 5 among 336; and the Menactra Group had 2 among 338. Deaths are listed as 0 in all three groups. These are participant counts as recorded, not a complete description of event timing, duration, severity beyond the serious classification, or relationship to vaccination.

The record also lists other adverse event counts: 232 of 337 in the Nimenrix Lot A Group, 219 of 336 in the Nimenrix Lot B Group, and 234 of 338 in the Menactra Group. The registry’s serious-event term list includes Appendicitis and Pneumonia at 0.6% each, and Asthma, Hypoxia, Influenza, and Tooth infection at 0.3% each. The record does not supply further detail about the denominator or event-level context for these term percentages in the information.

These figures are descriptive. Comparing counts without complete follow-up, definitions, participant-level data, and a prespecified safety analysis does not establish why events occurred or whether group differences are meaningful. The adverse-event group labels in the registry use Nimenrix, while the study description names GSK 134612; the record does not explain this labeling difference.

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

This record establishes that a randomized, quadruple-masked, parallel-group phase 2 study was conducted to evaluate the immunogenicity and safety of one dose of GSK 134612 compared with one dose of Menactra® in healthy subjects aged 10-25 years. It also establishes that the study included two GSK 134612 lots and defined a Month 1 antibody-response endpoint using baseline-dependent criteria. These registry entries describe the trial question and its measurement strategy, not the result of the comparison.

The primary response counts, group-specific estimates, and confidence intervals are not reported in the registry record. Without them, the record does not show how often participants met the response definition, whether the groups differed, or how precisely a difference was estimated. The trial’s randomized design cannot substitute for those missing results. Nor can the endpoint definition alone establish the pattern across all four serogroups.

The safety record includes serious adverse event counts and deaths, as well as other adverse event counts and several listed serious-event terms. Those figures describe recorded events in the named groups. They do not, on their own, establish that an event was caused by a vaccine, determine the comparative safety of the groups, or characterize every aspect of the safety experience. The registry record does not provide a complete account of event timing, exposure, follow-up, or statistical safety analyses.

More generally, statistical significance and clinical interpretation are different questions. A statistical comparison, when available, would address compatibility of the observed data with a specified model; a confidence interval would communicate the precision of an estimated contrast. Neither can be assessed for the primary immunogenicity result from the information recorded. The posted sample-size calculations are planning illustrations, not outcomes or observed power.

The careful conclusion is therefore limited: the study design, endpoint definition, analysis-cohort description, and selected safety counts are documented, but the registry information does not permit a conclusion about the comparative immunogenicity result or a full comparative safety assessment.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a study with more than one comparison embedded in its design. It had two lots of GSK 134612 and a Menactra® group, while its stated aims included both lot-to-lot immunogenicity comparison and comparison with the comparator vaccine. The primary response outcome also spans four serogroups, and the secondary outcomes include additional antibody measures and safety endpoints. This structure makes a clearly specified analysis plan important for understanding which comparisons are central and how uncertainty is controlled across multiple results.

The endpoint illustrates how a clinical outcome can depend on baseline status. Participants initially seronegative and seropositive were assessed using different response rules, while the reported endpoint counted participants meeting the applicable criterion. That choice makes the outcome easier to summarize as a response count, but it does not convey the full antibody-titer distribution. Separate titers and serogroup-specific results can help describe dimensions that a single response classification may obscure.

The registry also names an According-to-Protocol cohort rather than describing only the randomized enrollment. That distinction matters because analyses based on evaluable participants can have a different interpretation from analyses including all randomized participants. Clear reporting of cohort size, exclusions, assay availability, and missing-data handling is needed to understand the analysis population.

Finally, the record demonstrates why a design and endpoint definition should not be mistaken for evidence of an effect. Randomization and masking describe safeguards in the study structure; they do not supply the missing outcome estimates. The recorded safety counts offer useful descriptive information, but the primary immunogenicity results and their precision are not reported in the registry record. Statistical interpretation depends on both sound design and transparent outcome reporting.

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 trial-specific limitation in the registry information is that the primary immunogenicity outcome is described without its group results. No response counts, comparison estimates, confidence intervals, or p-values are reported. The stated primary outcome covers several serogroups, and the record notes that it is not reduced to one comparison. As a result, the comparative immunogenicity question cannot be answered from the registry record alone.

The analysis-population description is incomplete. It identifies an According-to-Protocol immunogenicity cohort and says participants had assay results for at least one study vaccine antigen component, but the text is truncated. The numbers included for each group and each serogroup, reasons for exclusion, and handling of missing assay results are not reported in the registry record. These details are important because the primary endpoint depends on post-vaccination assay measurements and baseline antibody status.

The registry describes the design as quadruple-masked and the study as observer-blind, but does not explain the roles covered by masking. The record does not report allocation concealment, the detailed statistical analysis plan, sample-size justification, interim analyses, or methods for controlling multiplicity. The posted sample-size assumptions are explicitly planning illustrations and cannot fill in the trial’s own design justification.

Safety information is also limited to selected counts and listed serious-event terms. The registry does not provide a full event-level account, detailed follow-up, or comparative safety analyses in the information available. In addition, adverse-event group labels use Nimenrix while the study description names GSK 134612; the reason for that difference is not reported in the registry record. These limitations restrict interpretation of both the immunogenicity and safety evidence.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety Study of GSK Biologicals' Meningococcal Vaccine GSK 134612 Versus Menactra® in Healthy Adolescents/Adults — NCT01165242.
• Registry record last updated 2018-06-26; status last verified 2018-05.
• Results first posted 2017-06-08.
• 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

NCT01165242 is listed as a completed, randomized, quadruple-masked, parallel-group phase 2 study sponsored by GlaxoSmithKline. It enrolled 1013 healthy subjects aged 10-25 years and compared one dose of GSK 134612 with one dose of Menactra®, with separate GSK 134612 Lot A and Lot B groups. The study start date was 2010-08-19, and primary completion was 2011-02-25.

The primary endpoint counted participants meeting a baseline-dependent hSBA vaccine-response definition one month after vaccination for serogroups A, C, W-135, and Y. The primary immunogenicity analysis was described as using an According-to-Protocol cohort. The registry also lists antibody and safety outcomes. It reports selected adverse-event counts and terms, but does not report primary endpoint results, a statistical comparison, or a complete analysis plan. The record’s adverse-event group labels differ from the vaccine name used in the study description, and the reason is not reported in the registry record.