Safety and Immunogenicity of the Liquid Formulation of Group B Streptococcus Trivalent Vaccine and of the Lyophilized Formulation of Group B Streptococcus Trivalent Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of the Liquid Formulation of Group B Streptococcus Trivalent Vaccine and of the Lyophilized Formulation of Group B Streptococcus Trivalent Vaccine (NCT02270944), a randomized phase 2 study. The primary outcome is Concentration of Serotype Ia GBS IgG Levels in Healthy Non-pregnant Women.

2. Clinical Question

The clinical question is about immunogenicity and safety in the study population, not about prevention of infection or clinical outcomes. The primary endpoint is a laboratory measure of antibody concentration. The registry identifies geometric mean concentrations, expressed in micrograms per milliliter, and reports a comparison of the two formulations using a ratio of geometric mean concentrations.

The registry also lists secondary safety outcomes: subjects reporting solicited local and systemic adverse events, any unsolicited adverse events, and serious adverse events. These outcomes provide additional information about events recorded during the study, but they are distinct from the primary antibody endpoint. The record does not report a clinical endpoint measuring prevention of Group B Streptococcus infection.

3. Trial Design

This was a Phase II, randomized, comparative, observer-blind, multicenter study with a parallel-group design. It enrolled 1053 healthy non-pregnant women aged 18 to 40 years and is listed as completed. The study compared a single dose of liquid Group B Streptococcus trivalent vaccine with a single dose of its lyophilized formulation.

The registry describes masking as triple, but does not identify which specific groups of people were masked. It also does not report the randomization procedure, allocation ratio, or details of how the study sites were selected. These details are not reported in the registry record. The parallel design means that the two formulations were assigned to different groups rather than given sequentially to the same participants.

The primary outcome was serotype Ia Group B Streptococcus IgG antibody concentration at Day 31 after a single vaccination. Antibody concentrations were measured using an enzyme-linked immunosorbent assay and summarized as geometric mean concentrations. The registry reports 521 participants in the liquid group and 513 in the lyophilized group for the primary endpoint. The safety summaries use groups of 526 and 521, respectively. The record does not explain the difference between the endpoint analysis counts and the safety counts.

The study also listed three secondary safety outcomes covering solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events. The registry lists six outcome measures and three analyses. Further information about the full set of measures and the statistical plan is 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: Among the 1053 subjects enrolled in the study, 3 subjects were randomized but didn't receive the vaccine. The 3 subjects were excluded and didn't start the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All subjects in the Full Analysis Set immunogenicity population who received the study vaccine, have no major protocol deviation or other reasons to be excluded as defined prior to unblinding \& provided evaluable serum samples both before vaccination and at Day 31 in the protocol required windows.

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 Concentration of Serotype Ia GBS IgG Levels in Healthy Non-pregnant Women, measured over At Day 31 after a single vaccination.

The primary endpoint measures the concentration of serotype Ia-specific Group B Streptococcus IgG antibodies in serum at Day 31 after one vaccination. The registry reports the result in micrograms per milliliter and summarizes each group using a geometric mean concentration, or GMC. It states that antibody concentrations were measured by enzyme-linked immunosorbent assay.

A geometric mean is a way to summarize measurements that are positive and may vary multiplicatively. Rather than describing a typical participant by an arithmetic average, it summarizes values on a logarithmic scale and expresses the result back on the original scale. This can be useful for antibody concentrations, where measurements may be unevenly distributed. This is a general explanation of the statistic, not an additional description of the study’s analysis.

The endpoint is used to compare the antibody response associated with the two formulations. The registry reports a GMC of 6.81 µg/mL for the liquid formulation and 6.66 µg/mL for the lyophilized formulation, with a 95% confidence interval for each group’s GMC. It also reports an ANCOVA comparison as a ratio of GMCs. These results describe antibody concentrations at the stated time point; they do not directly measure prevention of infection or establish a clinical benefit.

The primary analysis population was restricted to participants who received vaccine and had evaluable serum samples before vaccination and at Day 31 within the protocol-required windows, with exclusions for major protocol deviations or other reasons defined before unblinding. The record does not report further detail about the assay’s measurement limits or handling of values outside them.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical summary for the primary endpoint is the geometric mean concentration. The study measured serum IgG antibody concentrations and expressed them in µg/mL. A geometric mean is generally appropriate for positive measurements that are better described by relative changes than by equal absolute increments. In general, the calculation works on logarithmically transformed values and then returns to the original measurement scale. The registry identifies the endpoint as a GMC but does not report every computational detail of that summary.

What does a confidence interval convey?

The registry reports 95% confidence intervals for each group’s GMC and for the ratio of GMCs. In general, a confidence interval describes the statistical uncertainty around an estimate under the model and assumptions used. It is not a guarantee that the true value lies in the interval, nor does it describe the spread of individual antibody measurements. The group intervals are 5.54 to 8.37 µg/mL for the liquid formulation and 5.4 to 8.21 µg/mL for the lyophilized formulation. The comparative interval is 0.79 to 1.32 for the ratio of GMCs, with a point estimate of 1.02.

Why use a ratio for the comparison?

A ratio places the comparison on a relative scale. A ratio of 1 represents equal values for the groups; values above or below 1 represent relative differences in opposite directions. This is a general interpretation of ratios, not a claim about the trial’s decision rule. Here, the reported ANCOVA ratio is 1.02. Its confidence interval spans 1, so the posted estimate is compatible with equal GMCs as well as with values on either side of equality. The registry does not report a p-value for this analysis.

What does ANCOVA contribute?

The reported comparison uses ANCOVA, or analysis of covariance, to estimate the ratio of GMCs. In general, an analysis of covariance can account for selected covariates when comparing groups, potentially improving precision or adjusting for baseline differences. The covariates and model specification used in this study are not reported in the registry record. It is therefore not possible to determine from the record which factors were included, whether baseline antibody concentration was included, or how the model handled the antibody measurements. The adjusted analysis should be understood as the sponsor’s reported comparison, with those details unavailable.

How should the non-inferiority or equivalence label be read?

The legacy analysis classification says that the comparison is associated with a non-inferiority or equivalence analysis. In general, such an analysis requires a prespecified margin or bounds defining what difference is acceptable, as well as a decision rule based on the estimate and confidence interval. The margin, bounds, and decision rule are not reported in the registry record. The ratio and interval alone cannot establish that a formal criterion was satisfied. The record also does not report the protocol’s sample-size justification or any interim analyses.

What is the role of the endpoint population?

The primary analysis population includes participants in the Full Analysis Set immunogenicity population who received the study vaccine, had no major protocol deviation or other prespecified exclusion, and had evaluable serum samples before vaccination and at Day 31 within the required windows. This definition makes the reported endpoint dependent on available, appropriately timed samples and the stated exclusions. The registry does not report the number excluded for each reason, the amount or pattern of missing data, or a sensitivity analysis for missing measurements. Consequently, the record does not show how results might differ under other analysis populations or assumptions about missing measurements.

How do planning illustrations differ from trial power?

The sample-size section presents planning illustrations calculated from an observed effect under stated assumptions: two-sided significance level 0.05, equal allocation, and a normal approximation. In general, these illustrations ask what sample size would be associated with detecting a specified fraction of an observed effect under those assumptions. They are not evidence that the trial was designed around that effect, and they are not observed power. The registry does not report the original sample-size justification. The illustrations should therefore be read as hypothetical planning aids, not as a retrospective assessment of whether the study was adequately powered.

More generally, statistical estimates depend on both the observed data and the choices made in measurement, population definition, and modeling. The reported GMCs and ANCOVA ratio provide a concise account of the primary outcome, while the registry’s missing detail limits independent evaluation of the model and the formal comparison framework. Those limitations do not alter the values posted; they define what can and cannot be concluded from the available record.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as an ANCOVA estimate of the ratio of GMCs. The estimate is 1.02, with a 95% confidence interval from 0.79 to 1.32. This is the sponsor’s posted analysis and is the appropriate result to foreground when describing the trial’s primary comparative result. The registry does not report a p-value for this analysis.

The page also includes calculated tables, plots, and planning illustrations. These displays help readers inspect the posted results, but they do not replace the sponsor’s adjusted ANCOVA analysis. No separate recalculated comparison is identified in the record here, so there is no alternative numerical estimate to set against the sponsor’s result. The group GMCs and their confidence intervals can be described directly, while recognizing that they are not the same as the adjusted ratio analysis.

The legacy classification associates the analysis with non-inferiority or equivalence, but the registry does not report the margin, bounds, or decision rule. Accordingly, the reported ratio should not be turned into a categorical formal conclusion based on the label alone. The posted analysis describes the estimate and its uncertainty; the missing decision criteria prevent independent confirmation of a non-inferiority or equivalence conclusion.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and three analyses. It names three secondary safety outcomes: the number of subjects reporting solicited local and systemic adverse events, any unsolicited adverse events, and any serious adverse events. The record does not provide a full statistical analysis plan or say how testing across these outcomes was handled. Any multiplicity adjustment, hierarchy of outcomes, or prespecified testing sequence is not reported in the registry record.

Multiplicity matters in general when several outcomes or comparisons are examined, because repeated testing can affect the chance of finding apparently notable results. This is a general statistical consideration, not a claim that the trial did or did not use a particular adjustment. Without the statistical plan, it is not possible to determine whether the three reported analyses correspond to all planned analyses or how they relate to the six outcome measures.

The primary endpoint population required evaluable samples before vaccination and at Day 31 within the protocol-required windows. It also excluded participants with major protocol deviations or other reasons defined before unblinding. The number of participants excluded for each reason, the amount of missing endpoint data, and the approach to missing measurements are not reported in the registry record. The record also does not report sensitivity analyses that would show how robust the primary result is to different assumptions about missing data or analysis-population definitions.

The primary endpoint counts are 521 for the liquid formulation and 513 for the lyophilized formulation. The safety summaries use 526 and 521. The registry does not explain these differences or give a participant flow account connecting enrollment, vaccination, endpoint availability, and safety follow-up. It is therefore important to keep the endpoint and safety denominators distinct rather than infer why they differ.

The registry does not report the original sample-size justification, the non-inferiority margin or equivalence bounds, or details of interim analyses. These absences limit assessment of the planned inferential framework. They do not change the posted estimates, but they restrict what can be concluded about the prespecified testing strategy and the handling of incomplete observations.

12. 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: abdominal adhesions (0.2%), abdominal pain upper (0.2%), nausea (0.2%), vomiting (0.2%), gastroenteritis viral (0.2%).

The safety summary reports serious adverse events among 6 of 526 participants in the liquid formulation group and 9 of 521 participants in the lyophilized formulation group. It reports zero deaths in each group. These are counts of participants recorded with serious adverse events in the registry’s safety summary; they are not the primary immunogenicity endpoint and should be interpreted separately from the antibody concentration results.

The registry also lists serious adverse-event terms, each shown with a frequency of 0.2%: abdominal adhesions, upper abdominal pain, nausea, vomiting, viral gastroenteritis, and pharyngitis. These terms describe events recorded in the safety data. The record does not provide information about event timing, duration, outcome, relatedness to vaccination, or whether a participant could have had more than one event. It also does not establish that the listed terms represent every serious adverse event reported.

Counts alone do not establish whether an event was caused by a vaccine formulation. The figures should be read as reported safety observations within the study, not as a causal comparison or a complete assessment of risk. The registry’s secondary outcomes also include solicited local and systemic adverse events and unsolicited adverse events, but their detailed results are not included in the registry record.

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

The results show that the two groups had similar-looking posted Day 31 serotype Ia IgG geometric mean concentrations: 6.81 µg/mL for the liquid formulation and 6.66 µg/mL for the lyophilized formulation. The sponsor’s ANCOVA comparison gives a ratio of GMCs of 1.02, with a 95% confidence interval from 0.79 to 1.32. That interval communicates uncertainty around the comparative estimate and includes values below and above 1.

These findings describe the measured antibody response in healthy non-pregnant women aged 18 to 40 years who met the primary analysis population criteria. They do not directly tell us whether either formulation prevents infection, how long antibody levels persist beyond the reported time point, or what the results would be in populations not studied. The registry does not report a clinical infection endpoint or a longer-term primary antibody assessment.

The legacy record labels the analysis as non-inferiority or equivalence, but a formal conclusion requires the prespecified margin or bounds and decision rule. Those details are not reported in the registry record. Therefore, the ratio and confidence interval should be presented as the comparative statistical result without converting them into an independently verified non-inferiority or equivalence finding.

The safety summary records serious adverse events in both groups and no deaths. These observations are limited to the events and denominators shown in the registry summary. They do not establish cause, and the record does not provide all details needed to characterize event timing or relatedness. The result does not establish that one formulation is safer than the other.

In short, the page is about a measured immunogenicity endpoint and recorded safety observations in a specific trial population. The statistical estimates are informative descriptions, but they are not substitutes for missing clinical outcomes, analysis details, or decision criteria.

14. Why This Trial Matters Statistically

This trial offers a clear example of how a formulation comparison can focus on a laboratory endpoint rather than a clinical event. Both groups received a single dose of a Group B Streptococcus trivalent vaccine, with the study comparing liquid and lyophilized formulations. The primary outcome was a serotype-specific antibody concentration at a defined post-vaccination time point, summarized through geometric means.

Statistically, it illustrates why readers should distinguish group summaries from the comparative estimate. The GMCs and their confidence intervals describe each group; the ANCOVA ratio is the posted adjusted comparison. Those summaries answer related but different questions. The ratio’s confidence interval also shows why a point estimate close to 1 should not be read without considering uncertainty.

The record is also a useful example of the limits of a registry label. Although the analysis is classified as non-inferiority or equivalence, the margin and decision rule are unavailable in the registry record. Recognizing that distinction helps prevent readers from treating an analysis label as a conclusion. Similarly, a planning illustration based on an observed effect is not evidence of the original design justification or of observed power.

Finally, the separate endpoint and safety analysis counts illustrate why denominators matter. The primary immunogenicity results and safety summaries do not use the same counts, and the record does not explain why. Keeping the populations distinct, while noting the missing flow information, supports a more careful reading of the reported estimates.

15. 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 registry record leaves important details about the primary analysis unspecified. It reports ANCOVA but not the covariates, model specification, or other analysis choices. It also does not report the non-inferiority margin or equivalence bounds, the decision rule, or a p-value. These omissions limit independent evaluation of the formal comparative claim, even though the ratio and confidence interval are reported.

The primary endpoint population required evaluable serum samples before vaccination and at Day 31 and excluded participants with major protocol deviations or other prespecified reasons. The registry does not report how many participants were excluded, how many lacked evaluable measurements, or whether sensitivity analyses were performed. The endpoint counts differ from the safety counts, but the record does not explain the participant flow or the reasons for the distinct denominators.

The study’s masking is recorded as triple, but the record does not identify who was masked. Details of randomization, allocation ratio, site selection, and the sample-size justification are not reported in the registry record. The registry also does not report whether interim analyses were performed or how multiplicity across outcomes was addressed.

The primary endpoint is a Day 31 antibody measurement, not a clinical infection outcome. The information presented therefore does not show prevention of disease or persistence of antibody response beyond that time point. The safety summary lists serious adverse-event counts, selected terms, and deaths, but does not provide event timing, duration, outcome, or relatedness in the registry record. These limits constrain interpretation of both efficacy-related and safety-related questions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of the Liquid Formulation of Group B Streptococcus Trivalent Vaccine and of the Lyophilized Formulation of Group B Streptococcus Trivalent Vaccine — NCT02270944.
• Registry record last updated 2019-12-05; status last verified 2019-11.
• Results first posted 2017-07-28.
• 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.

19. Record Summary

This completed Phase II randomized, parallel, observer-blind, multicenter study compared a single dose of liquid Group B Streptococcus trivalent vaccine with a single dose of the lyophilized formulation in healthy non-pregnant women aged 18 to 40 years. Enrollment was 1053.

The primary endpoint was serotype Ia Group B Streptococcus IgG concentration at Day 31, measured by enzyme-linked immunosorbent assay and summarized as a geometric mean concentration. The registry reports group GMCs of 6.81 µg/mL and 6.66 µg/mL, and an ANCOVA ratio of GMCs of 1.02 with a 95% confidence interval from 0.79 to 1.32.

Serious adverse events were reported for 6 of 526 participants in the liquid group and 9 of 521 in the lyophilized group; zero deaths were reported in each group. Important details, including the formal non-inferiority or equivalence criteria and explanations for the different analysis counts, are not reported in the registry record.