Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Conjugate Vaccine (GSK134612) When Co-administered With Boostrix® in Subjects Between 11 and 25 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Conjugate Vaccine (GSK134612) When Co-administered With Boostrix® in Subjects Between 11 and 25 Years of Age (NCT01767376), a randomized phase 3 study. The primary outcome is Anti-Meningitis Antibody Titers by Serum Bactericidal Assay Using Rabbit Complement (rSBA).

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group phase 3 study. It enrolled 692 participants and is listed as completed. The recorded study start date is 2013-01-10, and the primary completion date is 2014-01-16. The sponsor was GlaxoSmithKline. The record does not identify which participants, investigators, or other personnel were masked.

The three groups differed in whether the meningococcal vaccine and Boostrix were administered at the same visit or one month apart. The Nimenrix+ Boostrix Group received one dose of each at Month 0. The Nimenrix Group received Nimenrix at Month 0 and Boostrix at Month 1. The Boostrix Group received Boostrix at Month 0 and Nimenrix at Month 1. The record describes the injections as intramuscular and given in the deltoid muscle.

The study purpose was to assess immunogenicity, safety and reactogenicity when the vaccines were co-administered, compared with each vaccine given separately. The listed primary endpoint concerns antibody titres after Nimenrix vaccination. For the two groups included in the primary results, that assessment was at Month 1; for the Boostrix-first group, the corresponding timing was Month 2. The primary outcome description explicitly limits its results to the Nimenrix+ Boostrix Group and Nimenrix Group.

The record also lists secondary outcomes covering meningococcal antibody titres and vaccine response, diphtheria and tetanus antibody concentrations, antibodies to pertussis antigens, booster responses, and solicited local and general symptoms. These outcomes address several aspects of immune response and short-term tolerability, but the record extract does not give their results. The trial design does not by itself establish that every listed outcome was analyzed in the same population or with the same statistical method; those details are not reported in the registry record.

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: During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms. Out of the 692 subjects enrolled in this study, one subject was eliminated due to not receiving vaccination, hence only 691 subject started the study.

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 will included all evaluable subjects from the ATP cohort for safety for whom assay results were available for antibodies against at least one study vaccine antigen component after at least one vaccine dose.

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 Anti-Meningitis Antibody Titers by Serum Bactericidal Assay Using Rabbit Complement (rSBA), measured over One month after Nimenrix vaccination (i.e. Month 1 for Nimenrix+Boostrix and Nimenrix Groups and Month 2 for Boostrix Group).

The primary endpoint is the geometric mean titre (GMT) of antibodies against meningococcal serogroups A, C, W-135 and Y. Titres were measured by serum bactericidal assay using rabbit complement and expressed in ELISA units per milliliter (EL.U/mL). The assessment was one month after Nimenrix vaccination: Month 1 for the Nimenrix+ Boostrix and Nimenrix groups, and Month 2 for the Boostrix group. The primary results were specified only for the first two groups.

A GMT summarizes titre measurements on a multiplicative scale. In general, this can be useful for antibody measurements that vary over a wide range: the geometric mean is based on averaging transformed values and then returning them to the original scale. It describes a group-level central tendency, not the titre of every participant or the proportion who reached a particular antibody threshold. The listed secondary outcomes include counts above cut-off values and vaccine responses, which address different questions from the primary GMT.

The record specifies a 95% confidence interval (CI) as the measure of dispersion. In general, a confidence interval conveys uncertainty around an estimated group-level quantity; it is not a guarantee that an individual participant's titre falls within the interval. The registry record does not report the GMT estimates or their confidence intervals. It therefore does not allow a reader to assess the antibody levels, the precision of the estimates, or the numerical contrast between the primary comparison groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a geometric mean rather than an arithmetic mean. In general, a geometric mean is appropriate for measurements that are naturally interpreted on a multiplicative scale, such as antibody titres that can span a broad range. The calculation uses transformed measurements, averages them on that scale, and converts the result back. Consequently, it summarizes the central tendency in a different way from simply adding all titres and dividing by the number of participants. The registry record identifies GMT as the parameter but does not describe the transformation or other computational details.

What does the assay measure?

The primary endpoint used a serum bactericidal assay with rabbit complement. The measured antibodies were directed against meningococcal serogroups A, C, W-135 and Y, and results were expressed in EL.U/mL. An assay-based antibody titre is a laboratory measurement, not a direct count of clinical infections or a measure of every aspect of immune response. In general, assay results need to be interpreted in the context of the specified assay, units, time point and population. The registry record provides those core endpoint details but does not provide the observed values.

The GMT is reported with a 95% confidence interval. In general, an interval estimate communicates uncertainty around an estimated parameter, conditional on the data and the statistical assumptions used. It helps distinguish the estimated group-level value from the uncertainty in that estimate. It is not a range containing 95% of individual participants' measurements. Since the GMTs and intervals are not reported in the registry record, neither the scale of the antibody response nor the precision of the estimates can be evaluated from this extract.

Why is the analysis time point important?

The primary assessment was one month after Nimenrix vaccination. That corresponds to Month 1 in the group receiving Nimenrix with Boostrix and the group receiving Nimenrix first, and Month 2 in the group receiving Boostrix first. Aligning measurement to the Nimenrix dose makes the stated timing interpretable in relation to that vaccine, while the calendar month differs between schedules. The primary results were limited to the co-administration and Nimenrix groups. The Boostrix-first group's endpoint timing is described, but it is not included in the primary results according to the record.

The primary endpoint is not a single combined measure across the four serogroups. The record names a GMT analysis for each serogroup. In general, multiple related outcomes can give a more detailed view of the measurements, while also creating multiple opportunities for statistical findings. How those outcomes were handled jointly, including whether any multiplicity adjustment was used, is not reported in the registry record.

What does randomization contribute?

Random allocation is intended, in general, to make treatment groups comparable on average with respect to measured and unmeasured baseline characteristics. It supports a fair comparison of assigned strategies, but it does not guarantee identical groups in a particular trial or remove the need to consider missing measurements and analysis-population choices. This record identifies the study as randomized and parallel-group. It does not report the randomization sequence method, concealment procedures, stratification factors, or group allocation details beyond the arm descriptions.

The study is listed as single-masked. In general, masking can limit the influence of expectations on participant reporting, investigator assessments or other trial processes, depending on who is masked. The record does not say which parties were masked or describe how masking was maintained. Therefore, the potential role of masking in specific outcome assessments cannot be evaluated from the registry record.

What is the role of the analysis population?

The primary immunogenicity analysis used an according-to-protocol cohort. The record defines it as including evaluable subjects from the according-to-protocol safety cohort for whom assay results were available for antibodies against at least one study vaccine antigen component after at least one vaccine dose. In general, such a population focuses an immunogenicity analysis on participants meeting specified evaluation conditions. It may differ from an analysis of all randomized participants. The record does not give the cohort size, the number of participants with results for each serogroup, or the reasons participants might not have been evaluable.

Analysis-population definitions affect the interpretation of estimates. If participants without available measurements are omitted, the estimate describes the analyzed participants rather than automatically describing everyone enrolled. General statistical practice calls for reporting the analysis population, the amount and pattern of missing data, and how missing measurements were handled. The cohort definition is reported, but the missing-data methods and participant flow details are not reported in the registry record.

How should planning illustrations be read?

Any sample-size illustration is a planning calculation, not an observed trial result and not a measure of the trial's observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set to a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is to give the total number of events; for other outcomes, it is participants per arm. Those are general planning assumptions, not evidence that the trial was designed using them. The trial's own sample-size justification and design assumptions are not reported in the registry record.

In general, planning calculations depend on the effect considered meaningful or worth detecting, the variability of the outcome, the significance level, the desired power and the design. Illustrations that scale an observed effect are conditional scenarios, not proof that a trial had sufficient power for a particular clinical or statistical question. The record does not provide a single reduced primary comparison for such an illustration, and the primary outcome has multiple serogroup categories and time points. No specific sample-size planning value should therefore be treated as an observed finding or as the trial's original justification.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint covers four meningococcal serogroups, and the registry record lists additional secondary outcomes for antibody titres, vaccine response, other antibody concentrations, booster responses and solicited symptoms. It reports 14 outcome measures and 9 analyses. Multiple outcomes create multiple opportunities to observe an apparently unusual result. In general, a multiplicity strategy may control the overall chance of false-positive conclusions, prioritize outcomes, or frame results as exploratory. Whether any adjustment or hierarchy was prespecified is not reported in the registry record. The record also does not describe interim analyses or a detailed statistical analysis plan.

The primary immunogenicity population is described as an according-to-protocol cohort with available assay results after at least one vaccine dose. That definition identifies an eligibility rule for analysis, but not how many enrolled participants met it. The number of missing antibody measurements, their distribution across groups or serogroups, and the methods used to handle missing data are not reported in the registry record. It is therefore not possible to determine from this information whether missingness could have affected the primary estimates.

Randomization is reported, but the record does not state whether the primary analysis followed assignment regardless of protocol adherence or used another approach beyond the stated according-to-protocol cohort. It also does not report the statistical tests, model specification, covariate adjustment, or any criteria for declaring a result successful. The GMT and 95% confidence interval are specified, but the analysis details needed to reproduce or fully evaluate those estimates are not reported. These omissions do not establish that the analyses were not conducted; they mean the 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastroenteritis (0.4%), orthostatic intolerance (0.4%), depression (0.4%).

The registry record reports serious adverse events by group using the number at risk and the number affected. In the Nimenrix+ Boostrix Group, 0 of 231 participants had a serious adverse event. In the Nimenrix Group, 0 of 228 had a serious adverse event. In the Boostrix Group, 3 of 232 had a serious adverse event. Deaths were 0 in all three groups. These figures are descriptive counts; they do not alone establish whether an event was caused by a vaccine.

The record lists gastroenteritis, orthostatic intolerance and depression as the top serious adverse-event terms, each reported as 0.4%. The extract does not specify further event-level details, such as timing, duration, outcome or an individual causal assessment. It also does not provide the complete set of event narratives or clarify how the top terms relate to the affected-participant counts.

The separate counts for other adverse events were 190 of 231 in the Nimenrix+ Boostrix Group, 166 of 228 in the Nimenrix Group, and 180 of 232 in the Boostrix Group. These are registry counts for the category labeled other adverse events, not the serious-event counts. Without definitions, observation periods and event-level information, the counts should not be interpreted as a comparison of severity or as proof of a causal difference. Solicited local and general symptoms are listed as secondary outcomes, but their results are not reported in the record extract.

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

This study was designed to compare immunogenicity, safety and reactogenicity when Nimenrix and Boostrix were given together or separately in healthy adolescents and young adults. Its primary outcome was specified as GMT antibody titres against four meningococcal serogroups at a defined time after Nimenrix vaccination. The registry record also documents the randomized, parallel-group design, the schedules, the immunogenicity analysis population and descriptive adverse-event counts.

The record does not report the primary GMT estimates or their confidence intervals. It therefore does not show the antibody titre levels observed in the primary comparison, the precision of those estimates, or whether the group estimates differed. No conclusion about the primary immunogenicity comparison can be drawn from the endpoint description alone. The record also does not provide the results for the listed secondary immunogenicity and reactogenicity outcomes.

The serious adverse-event counts and death counts are descriptive safety information. They provide a record of the numbers reported in each study group, but do not by themselves establish causation or exclude uncommon risks. The other adverse-event counts are a separate category and should not be conflated with serious adverse events. The record extract does not give enough event-level information to interpret every reported event in context.

In general, trial results apply most directly to the population and procedures studied. The participants were described as healthy and between and including 11 and 25 years of age. The registry record does not establish how findings would apply to other populations, and the missing outcome estimates prevent assessment of the findings even for the enrolled study population. The study's completion status indicates that the trial is listed as completed; completion status is not itself evidence of a particular result.

Overall, the registry description supports understanding of the research question and design, but not a conclusion about the primary result. Outcome estimates, uncertainty intervals, multiplicity handling and missing-data details would be needed for a fuller statistical interpretation. No treatment recommendation follows from these registry entries.

13. Why This Trial Matters Statistically

The statistical structure of this trial illustrates why a clear outcome definition is only one part of interpreting a randomized study. The registry record specifies the assay, units, antibody targets, summary measure and measurement timing. These details let readers understand what the primary endpoint was intended to represent and distinguish it from secondary outcomes based on cut-off values, vaccine response or symptoms.

The design also makes the timing of the comparison important. One group received both vaccines at Month 0, while the two separate-vaccine schedules placed Nimenrix at different calendar months. The primary assessment was defined relative to Nimenrix vaccination, and the primary results were limited to the co-administration and Nimenrix groups. A reader should therefore distinguish the endpoint's timing relative to vaccination from the numbered study month.

The record identifies randomization and a single-masked design, while leaving important implementation details unspecified. It also defines an according-to-protocol immunogenicity cohort, but does not report its size or the handling of unavailable measurements. These are useful reminders that a treatment-group comparison is interpreted through both the design and the population actually analyzed. In general, estimates can be precise yet still depend on the validity of those design and analysis choices.

Finally, this record demonstrates the difference between documenting a planned question and reporting its answer. The primary GMTs and confidence intervals are not reported, so the statistical results cannot be evaluated. The safety counts provide some descriptive information, but they cannot replace the missing immunogenicity estimates or a complete account of the secondary results. Statistical interpretation depends on the results and their uncertainty, not just the study title, endpoint, or completion status.

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 the registry record does not report the primary GMT estimates or 95% confidence intervals. The assay, serogroups, units, time points and stated comparison are described, but the values needed to evaluate the comparison are absent. The listed secondary outcomes are likewise not accompanied by results in this record extract.

The immunogenicity analysis population is defined, but its size and participant flow are not reported. The number of participants with available results for each serogroup, reasons for exclusions, and methods for handling missing measurements are also not reported in the registry record. These details matter because the analysis population may not include every enrolled participant.

Although allocation is described as randomized and masking as single, the sequence-generation and allocation-concealment methods are not reported. The identity of the masked parties is not reported either. The statistical analysis plan, multiplicity approach, interim analyses, hypothesis-testing details and trial-specific sample-size justification are not reported in the registry record. The planning assumptions listed for illustrations should not be mistaken for the trial's original design rationale.

Safety information in the record is limited to counts, deaths and selected serious-event terms with percentages. Further details about event timing, duration, severity grading, causal assessment and observation periods are not reported. The registry record lists solicited local and general symptoms as outcomes but does not provide their results. Consequently, the safety description is informative but incomplete for detailed comparisons.

The population was described as healthy subjects between and including 11 and 25 years of age. The record does not establish whether the findings apply to populations outside that description. More fundamentally, without the outcome estimates and fuller analysis details, this registry information cannot support a complete assessment of the trial's statistical findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Conjugate Vaccine (GSK134612) When Co-administered With Boostrix® in Subjects Between 11 and 25 Years of Age — NCT01767376.
• Registry record last updated 2017-09-06; status last verified 2017-08.
• Results first posted 2017-09-06.
• 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

This completed, randomized, single-masked, parallel-group phase 3 study enrolled 692 healthy participants between and including 11 and 25 years of age. It compared co-administration of Nimenrix and Boostrix with schedules in which the vaccines were given separately. The primary endpoint was the GMT of antibodies against meningococcal serogroups A, C, W-135 and Y, measured by serum bactericidal assay using rabbit complement and expressed in EL.U/mL.

The primary assessment was one month after Nimenrix vaccination, and the primary results were specified for the Nimenrix+ Boostrix and Nimenrix groups. The record defines an according-to-protocol immunogenicity cohort and reports descriptive safety counts. It does not report the primary GMT estimates, confidence intervals, detailed secondary results, or several analysis and missing-data methods. The available information therefore describes the study question and design more fully than it describes the observed immunogenicity findings.