Safety & Immunogenicity of 1 Dose of GSK134612 in Children 12-14 Months and 3-5 Years Old: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety & Immunogenicity of 1 Dose of GSK134612 in Children 12-14 Months and 3-5 Years Old (NCT00196976), a randomized phase 2 study. The primary outcome is Number of Subjects With an Immune Response to Different Meningococcal Serogroups.

2. Clinical Question

3. Trial Design

This completed Phase 2 study is recorded as randomized, single-masked and parallel, with enrollment of 461. The registry lists GlaxoSmithKline as the sponsor and gives the condition as meningococcal infections. The study start date is 2005-03-24 and primary completion is recorded as 2006-03-01.

The primary vaccination groups were organized by age and vaccine assignment. Healthy toddlers aged 12-14 months received one of four GSK134612A formulations or Meningitec™ as the control. Healthy children aged 3-5 years received one of the four formulations or Mencevax™ ACWY as the control. The arm descriptions specify intramuscular administration into the left arm for the primary GSK134612A groups and the toddler control, while the older-child control received Mencevax™ ACWY subcutaneously into the left upper arm.

The registry also describes booster groups. For toddlers, the descriptions refer to a booster dose of Mencevax™ ACWY 12 months after priming with formulation 1 or Meningitec™. For children aged 3-5 years, the listed booster-group descriptions state that no booster vaccination was received. These details should not be read as a complete account of all follow-up or procedures: the full protocol is not reported in the registry record.

The study's stated purpose was to evaluate immunogenicity, safety and reactogenicity after one dose, with formulation selection based on data up to one month after vaccination. The primary outcome timeframe is one month after the first dose. Although the record identifies the design as randomized and single-masked, the randomization procedure, allocation ratio, and identity of the masked parties 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.

Only the first 6 of 14 groups are shown.

Primary Study

Reasons for not completing this period:

Booster 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 data concerning immunogenicity measures were available.

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.

Only the first 6 of 15 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With an Immune Response to Different Meningococcal Serogroups, measured over One month after the first vaccine dose (Month 1).

The primary endpoint is the number of participants with an immune response to meningococcal serogroups A, C, W and Y, assessed one month after the first vaccine dose. Response was defined using serum bactericidal assay results with rabbit complement. For participants initially seronegative, with antibody titers < 1:8, a post-vaccination titer of at least 1:32 met the response definition. For participants initially seropositive, with titers at least 1:8, response required an increase of at least 4-fold from before to after vaccination.

This endpoint turns laboratory antibody measurements into a responder count using criteria that depend on the participant’s initial serostatus. Such a measure is used to describe whether antibody levels reached a specified threshold or rose by a specified amount; it is not itself a measure of clinical disease prevention. General explanation: immune-response endpoints can help compare vaccine formulations in an early clinical study, but interpretation depends on the assay, response definition, population analyzed and timing of measurement.

The endpoint is reported as a count of participants, and the stated analysis population is the According-to-Protocol cohort for immunogenicity. The registry record does not report the responder counts, the denominators used for each serogroup, or a statistical comparison among formulations. It therefore does not establish which formulation had the larger response or how precisely any difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design labels identify a randomized, single-masked, parallel study. Randomization is intended, in general, to reduce systematic differences between assigned groups by using a chance-based assignment process. A parallel design means that participants are assigned to a study group rather than all receiving each assigned intervention in sequence. The registry record does not describe how randomization was carried out, how assignments were concealed, or who was masked. Those details are not reported in the registry record.

What does the primary endpoint count?

The primary outcome is a count of participants meeting an immune-response definition for each of four meningococcal serogroups. The definition accounts for starting antibody status. Initially seronegative participants had to reach a post-vaccination titer of at least 1:32, while initially seropositive participants had to achieve an increase of at least 4-fold. This means that the response classification is based on both baseline status and the post-vaccination measurement, rather than on a single common post-vaccination threshold for everyone.

The outcome description specifies serum bactericidal assay measurements using rabbit complement and gives the assessment time as one month after the first dose. General explanation: a binary endpoint such as responder or non-responder is easy to interpret as a participant count, but it compresses a continuous antibody measurement into categories. The chosen thresholds determine who is counted as a responder, and the number of responders alone does not convey the distribution of antibody titers.

Which analysis population is named?

The registry says the primary immunogenicity analysis used the According-to-Protocol cohort for immunogenicity. It describes this cohort as all evaluable subjects for whom immunogenicity data were available. This is an analysis-population definition, not a report of how many participants were included in each outcome analysis. The number analyzed by arm and serogroup is not reported in the registry record.

General explanation: an According-to-Protocol analysis may exclude participants who do not meet specified evaluability or protocol criteria. Such an analysis can describe outcomes among participants with usable data under those criteria, but its interpretation depends on the criteria and exclusions. The registry does not provide the full criteria or a participant flow showing exclusions and missing measurements.

What comparisons and uncertainty are available?

The registry provides no analyses for the listed outcomes and does not report the primary responder counts, effect estimates, confidence intervals or p-values. Consequently, a statistical comparison between each GSK134612A formulation and its control cannot be reconstructed from the record. The design is described as randomized, but that label does not substitute for a reported analysis.

General explanation: for a binary outcome, a comparison can be expressed using measures such as a difference in response proportions or a ratio of proportions. The choice of measure and its confidence interval would help communicate both the direction and precision of a contrast. Those quantities are not reported for the primary endpoint, and no recalculated comparison is available in the registry record.

How should multiple outcomes be considered?

The record lists 30 outcome measures, including several immune-response outcomes, antibody measurements and safety outcomes. Considering multiple endpoints or group contrasts can raise multiplicity concerns: when many statistical tests are performed, the chance of at least one apparently unusual result can increase. General explanation: studies may address this by defining a primary endpoint, prespecifying a testing strategy, or adjusting inference. The registry record does not report a multiplicity procedure or a statistical analysis plan. It is therefore not possible to determine how the many listed outcomes were intended to be interpreted together.

What does the safety information describe?

The safety entries give counts at risk and counts affected for serious and other events, alongside death counts by listed group. These are descriptive counts. General explanation: adverse-event comparisons require attention to the group denominators, definitions, observation periods and differences in follow-up. A raw count without an adequately specified comparison cannot establish that an event is more or less common in one assignment. The record does not report a formal comparative safety analysis or the statistical plan for these outcomes.

The sample-size assumptions in the record describe a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms and a normal approximation. The illustration is not the trial’s own design justification and is not observed power. The record does not report the trial’s original sample-size justification, so the planning information should not be treated as proof that the trial was designed or powered for a particular comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes alongside the primary immune-response endpoint. These include seroprotection and seropositivity measures, antibody titers and concentrations for meningococcal serogroups and polysaccharides, and anti-tetanus measures. The record lists 30 outcome measures, but does not report analyses for them. A statistical analysis plan or a multiplicity adjustment is not reported in the registry record.

General explanation: multiplicity matters when many outcomes, time points or group comparisons are tested. Without a prespecified testing strategy, isolated nominal findings can be difficult to interpret because multiple opportunities exist to observe a result that appears notable by chance. This concern cannot be quantified from the record, because the analyses and testing strategy are not reported.

The primary immunogenicity population is described as the According-to-Protocol cohort for immunogenicity, comprising evaluable subjects with available immunogenicity data. The registry does not report the number of participants analyzed for each serogroup, the reasons participants may have been excluded, or how missing immunogenicity measurements were handled. A missing-data method is not reported in the registry record. The number randomized and the number contributing to a particular endpoint need not be the same, but the record does not provide the outcome-specific participant flow needed to assess this.

In general, missingness can affect an estimate if the availability of measurements is related to participant characteristics or outcomes. The direction and size of any such effect cannot be inferred without information about missing data and the analysis approach. No imputation method, sensitivity analysis or other missing-data procedure is reported in the registry record.

The study is described as randomized, but the randomization method, allocation ratio and masking details are not reported. The full statistical analysis plan is also not reported in the registry record. These omissions limit assessment of how the listed outcomes were prioritized, how comparisons were conducted and how uncertainty was handled.

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: bronchiolitis (toddlers subgroup) (2.6%), maculo-papular rash (toddlers subgroup) (2.5%), laryngitis (toddlers subgroup) (2.5%), acute bronchitis (toddlers subgroup) (2.4%).

The registry presents safety counts by named primary and booster groups. For serious events, the toddler primary groups each list 1 affected participant, while each 3-5-year-old primary group lists 0. The listed booster groups show 0 serious-event-affected participants. Deaths are recorded as 0 for every listed group. These group-specific entries should be read as descriptive counts, not as evidence of a causal difference between assignments.

For other events, the record gives affected counts and at-risk counts for the primary groups and some toddler booster groups. The 3-5-year-old booster groups list 0 at risk and 0 affected for other events. Differences in counts should not be compared without considering the groups and recorded denominators; the registry does not report a formal statistical comparison or the event observation details needed to interpret such comparisons.

The record separately lists serious-event terms and percentages for the toddlers subgroup: bronchiolitis at 2.6%, maculo-papular rash at 2.5%, laryngitis at 2.5%, and acute bronchitis at 2.4%. It does not provide a treatment-specific breakdown or uncertainty for these percentages. General explanation: serious adverse events are not necessarily events caused by the intervention; causal attribution and comparative interpretation require further context. The registry record does not report that these listed events were caused by a vaccine.

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

This record establishes that the study was designed to assess immunogenicity, safety and reactogenicity of four MenACWY conjugate-vaccine formulations in healthy children aged 12-14 months and 3-5 years. It identifies the age-specific control vaccines, the one-month primary outcome timeframe and the criteria used to define an immune response. It also records selected safety counts for primary and booster groups.

It does not establish which formulation produced the largest immune response, whether any formulation differed from its control, or how precisely a comparative effect was estimated. The primary outcome results and statistical comparisons are not reported in the registry record. The stated intention to select a formulation based on data through one month does not reveal the selection or its evidential basis.

The response endpoint is a laboratory-defined immune measure. General explanation: a measured antibody response can be relevant to vaccine evaluation, but it is not identical to a demonstrated reduction in disease. The registry record does not report clinical disease outcomes or establish a clinical benefit. It also does not provide the results for the listed secondary immunogenicity measures.

The safety entries describe recorded counts, including serious-event counts and deaths by group. They do not supply a formal comparison or enough detail to infer that one vaccine assignment caused more or fewer events. The listed serious adverse-event terms and subgroup percentages likewise do not provide treatment-specific contrasts.

For a fuller interpretation, readers would need outcome-specific participant counts, group-level results, effect estimates and uncertainty intervals, along with details of missing data and the analysis plan. These items are not reported in the registry record. The available information therefore supports understanding what was studied and how the primary response was defined, but not a conclusion about comparative efficacy, immunogenicity results or comparative safety.

13. Why This Trial Matters Statistically

The study raises a useful statistical issue: the same immune-response endpoint can classify participants differently depending on their baseline serostatus. Initially seronegative participants were assessed against a post-vaccination threshold, whereas initially seropositive participants were assessed for a fold increase. Understanding that rule is essential before interpreting any responder count or comparing groups.

The trial also includes multiple formulations, two age groups and age-specific controls. This creates several potential contrasts and makes clear reporting of the prespecified primary question, analysis population and multiplicity strategy important. Although the registry identifies the primary outcome and analysis cohort, it does not report the comparisons or the approach to multiplicity.

Another statistical distinction is between an endpoint definition and an endpoint result. The record provides considerable detail about the laboratory response criterion, yet the primary responder counts and their uncertainty are not reported. Without these, the size and precision of any group differences cannot be assessed. This is a practical reminder that methodological detail does not replace the results needed for inference.

The safety information similarly illustrates why descriptive counts and comparative evidence are different. Group-specific counts can document what was recorded, but they do not establish a difference in risk without suitable analysis and context. The posted record supports describing the study structure and selected safety entries; it does not support a comparative conclusion about the four formulations.

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 central limitation of the registry record for statistical interpretation is that it does not report primary outcome results or analyses. Responder counts, group-specific denominators, comparisons and uncertainty estimates are absent. Secondary outcome results are also not reported, despite the listing of 30 outcome measures.

The analysis population is described as an According-to-Protocol immunogenicity cohort, but outcome-specific numbers analyzed and the criteria used to determine evaluability are not reported. Participant flow, reasons for exclusion, missing measurement patterns and missing-data methods are not reported in the registry record. These omissions prevent assessment of how the analyzed population relates to the randomized groups.

Although the study is labeled randomized and single-masked, details of sequence generation, allocation concealment and masking are not reported. The allocation ratio and full statistical analysis plan are also not reported. The record does not describe a multiplicity strategy for the several formulations, age groups, serogroups and listed outcomes.

The safety information is limited to group-level counts and a list of serious-event terms with percentages for the toddlers subgroup. Event-specific observation periods, treatment-specific breakdowns for the listed terms, comparative estimates and uncertainty are not reported. The record also does not report the protocol details needed to interpret the booster groups beyond their brief descriptions.

These limitations concern what can be concluded from the registry record; they do not establish that relevant analyses or documentation do not exist elsewhere. Such information is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety & Immunogenicity of 1 Dose of GSK134612 in Children 12-14 Months and 3-5 Years Old — NCT00196976.
• Registry record last updated 2018-06-08; status last verified 2017-04.
• Results first posted 2017-03-01.
• 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 2 study was randomized, single-masked and parallel, with enrollment of 461. It evaluated four formulations of GSK134612A in healthy toddlers aged 12-14 months and children aged 3-5 years, using Meningitec™ and Mencevax™ ACWY as age-specific controls. The primary endpoint counted participants meeting a serogroup-specific immune-response definition one month after the first dose.

The registry describes an According-to-Protocol immunogenicity cohort, lists 30 outcome measures and records 0 analyses. Primary and secondary outcome results are not reported in the registry record. Safety entries include serious and other event counts by group and 0 deaths in each listed group, but no formal comparative safety analysis is reported. The registry record therefore describes the study question, design and selected safety information, but does not permit assessment of comparative immunogenicity or safety estimates.