A Study on Safety and Immune Response of Investigational RSV OA Vaccine in Combination With Herpes Zoster Vaccine in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on Safety and Immune Response of Investigational RSV OA Vaccine in Combination With Herpes Zoster Vaccine in Healthy Adults (NCT05966090), a randomized phase 3 study. The primary outcome is Adjusted Geometric Mean Concentration (GMC) of Anti-glycoprotein E (gE) Antibodies at 1 Month Post-second Dose of HZ/su Vaccination.

2. Clinical Question

3. Trial Design

This is a Phase III, randomized, controlled, multi-country, open-label, parallel-group study sponsored by GlaxoSmithKline. The registry lists enrollment of 530 and a status of completed. The recorded start date is 2023-07-28 and the primary completion date is 2024-02-19. The study concerns respiratory syncytial virus and respiratory syncytial virus infections; its principal comparison focuses on the immune response to HZ/su when RSVPreF3 OA is given at the same visit as the first HZ/su dose or at a separate visit.

The co-administration group received both vaccines on Day 1 and the second HZ/su dose on Day 61. The control group received HZ/su on Day 1, RSVPreF3 OA on Day 31 and the second HZ/su dose on Day 61. The primary endpoint was assessed at 1 month post-second dose of HZ/su vaccination, identified as Day 91. Because the study is open-label, participants and study personnel were not masked to group assignment according to the registry. Randomization supports a comparison between assigned groups, but it does not by itself remove possible effects of awareness of assignment on subjective measures or study conduct.

The registry lists 199.0 participants in the co-administration group and 168.0 in the control group for the primary anti-gE endpoint. Those endpoint-specific analysis counts are not the same as the overall enrollment entry. The primary population is described as a per protocol set for HZ/su, with eligibility depending on vaccine receipt and availability of antibody measurements, among other conditions. The complete set of analysis-population criteria is not reported in the registry record.

The registry lists 16 outcome measures and 3 analyses. It does not report the study’s sample-size justification, the allocation ratio planned by the protocol, interim analyses or a full statistical analysis plan. Accordingly, the registry entries support a description of the recorded design and posted outcomes, not a reconstruction of every protocol decision.

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: A total of 530 eligible participants were randomized in a 1:1 ratio to either co-administration group or control group at Day 1.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per protocol set for HZ/su included all eligible participants in the exposed set who: received 2 doses of HZ/su vaccine, had immunogenicity results for anti-gE antibody concentrations, complied with the blood draw interval, without intercurrent medical conditions and without prohibited concomitant medication/vaccination, did not met any of the criteria for elimination up to blood sample collection. Participants with data available at the time of analysis were reported in this outcome measure.

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.

Population: Exposed set included all participants in the enrolled set who received at least 1 study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Adjusted Geometric Mean Concentration (GMC) of Anti-glycoprotein E (gE) Antibodies at 1 Month Post-second Dose of HZ/su Vaccination, measured over At 1 month post-second dose of HZ/su vaccination (Day 91).

The primary endpoint is the adjusted geometric mean concentration (GMC) of anti-glycoprotein E (gE) antibodies, measured at 1 month after the second HZ/su vaccination, on Day 91. The registry says anti-gE antibodies were measured with an enzyme linked immunosorbent assay (ELISA), with results expressed in mIU/mL. Glycoprotein E is the antibody target named for this HZ/su immune-response measure.

A GMC summarizes antibody concentrations on a logarithmic scale and returns the summary to the original measurement scale. This is useful when concentration measurements vary multiplicatively or are right-skewed rather than symmetrically distributed on their original scale. The word “adjusted” indicates that the reported summary is not simply identified as a raw group mean; however, the adjustment variables and model are not reported in the registry record.

Immune-response endpoints are used to characterize antibody response after vaccination. They are not, by themselves, measures of disease incidence or clinical protection. The endpoint is relevant to the question of whether the timing of RSVPreF3 OA alongside the first HZ/su dose is associated with the measured anti-gE response after the HZ/su course. It does not establish how long an antibody response persists beyond the stated measurement time, nor does it answer whether either vaccine prevents illness.

The registry reports 95% confidence intervals for the group GMCs and a sponsor-reported ratio analysis. A confidence interval communicates uncertainty around an estimate under the analysis assumptions; it is not a guarantee that the true value lies within the interval. The registry does not give the adjustment method or the noninferiority margin, so those elements cannot be independently assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean describe? Antibody concentrations are often analyzed after logarithmic transformation because differences between observations may be more naturally described as multiplicative than additive. A geometric mean is calculated on that transformed scale and then expressed back in the original units. The primary endpoint is an adjusted GMC in mIU/mL. The registry reports the concentrations and confidence intervals, but it does not report the adjustment covariates or model specification. Therefore, the group GMCs can be described as posted without reconstructing how adjustment was performed.

What does a confidence interval add? A confidence interval conveys the precision of an estimate under the statistical model and assumptions used. A narrower interval generally indicates greater precision than a wider interval, while the interval’s endpoints show values compatible with the data and method at the stated confidence level. It is not a range guaranteed to contain the true value, and it does not by itself determine whether a difference is important. The registry reports 95% confidence intervals for the primary group concentrations and for the sponsor’s ratio. The calculation method for those intervals is not reported in the registry record.

How should the ratio be read? A ratio compares quantities by division rather than subtraction. For a ratio of GMCs, the value’s interpretation depends on which group is in the numerator and which is in the denominator. The registry reports a ratio of 1.24 with a 95% confidence interval from 1.08 to 1.42 and labels the analysis noninferiority, but it does not identify the ratio orientation or the analysis method. A noninferiority analysis also requires a prespecified margin: a boundary defining how much difference can be accepted for the noninferiority question. That margin is not reported in the registry record. Thus, the label and estimate can be reported, but the noninferiority criterion cannot be independently checked from the record alone.

Why does randomization matter? Random assignment is intended to make the groups comparable with respect to factors that could affect outcomes, including factors not measured by the study. It can support a causal comparison of assigned strategies when implementation, follow-up and analysis are appropriate. Randomization does not ensure that every measured characteristic is exactly balanced, and it does not correct for missing outcomes or deviations from the planned analysis. The registry identifies the study as randomized but does not report the randomization sequence method or concealment procedures.

What is the role of the two-group recalculations? A recalculation from posted summary statistics is an unadjusted comparison. For a binary outcome such as a response percentage, a risk difference expresses the difference in group proportions, while a risk ratio compares those proportions as a ratio. These summaries can be informative but are not necessarily the sponsor’s prespecified model or estimand. They can also be imprecise when event counts are small. In this record, the recalculated secondary comparisons are not the primary sponsor analysis. No recalculated primary comparison is posted because the primary endpoint is not listed as estimable for a two-arm recalculation.

Why can over-dispersion matter? In general, a binary outcome model may assume that observed variability follows a particular probability distribution. Over-dispersion means the data vary more than that model expects. If it is ignored, standard errors can be too small and confidence intervals or p-values can appear more certain than warranted. This is a general statistical consideration, not a claim that over-dispersion occurred in this study. The registry record does not state whether over-dispersion was assessed or how it was handled.

How should p-values and confidence intervals be used? A p-value summarizes how unusual the observed data would be under a specified null hypothesis and model. It does not measure the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. A confidence interval provides an estimate and a range of uncertainty, which is often more useful for judging precision. For the recalculated secondary comparisons, p-values are unadjusted. They should therefore be read cautiously, particularly because the study lists multiple outcome measures and the registry does not report a multiplicity strategy.

What do planning illustrations mean? The registry’s planning illustrations use the observed effect as a reference and apply stated assumptions: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. Such illustrations indicate how a hypothetical future design might be sized under those assumptions. They are not evidence about the trial’s actual power, and they are not the study’s original sample-size justification. The record specifically identifies them as planning illustrations computed from the observed effect, not the trial’s own design.

What limits the methods assessment? The registry does not report a complete statistical analysis plan, the primary adjustment model, the ratio orientation, the noninferiority margin, or a multiplicity procedure. It also does not provide a full account of missing-data handling or the randomization implementation. These omissions mean that the posted summaries can be interpreted descriptively, but several features needed for a full independent methodological review are not reported in the registry record.

10. Analyses Reported by the Sponsor

The sponsor’s own primary analysis is reported as a noninferiority ratio of 1.24, with a 95% confidence interval from 1.08 to 1.42. The registry does not report a p-value for this analysis, the ratio’s orientation, the analysis method or the noninferiority margin. The primary arm GMCs and their confidence intervals are posted, but a simple unadjusted primary ratio is not listed as recalculated. The registry indicates that values were missing or not estimable for a two-arm comparison for this other endpoint.

The sponsor’s analysis and the recalculations for selected secondary outcomes are different kinds of evidence. The sponsor’s primary result is the reported analysis for the primary endpoint. The recalculations are simple, unadjusted comparisons based on posted summary statistics and do not recreate the sponsor’s adjustment or noninferiority procedure. No discrepancy is flagged for this record. The registry record does not provide enough methodological detail to independently assess whether the reported ratio satisfies the sponsor’s noninferiority criterion. The sponsor’s label should therefore be reported alongside, rather than replaced by, the available group estimates and the limits of what the record documents.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures and 3 analyses, including multiple immune-response outcomes and safety measures. When a study assesses many outcomes, the chance of finding at least one apparently notable result by chance can increase if each result is interpreted as a standalone confirmatory test. Statistical approaches such as a prespecified testing hierarchy or adjustment of significance thresholds can address this issue. The registry does not report whether any such approach was used, how outcomes were ordered, or which outcomes were intended to be confirmatory beyond the designated primary endpoint.

The secondary recalculated p-values are identified as unadjusted. They should not be read as accounting for the number of outcomes considered. This does not make the estimates unusable: effect estimates and confidence intervals can still describe the data. It does mean that isolated nominal significance, if present, would carry less weight without a reported multiplicity strategy and prespecified interpretation plan.

The primary population is described as a per protocol set for HZ/su, involving eligible participants who received 2 doses, had anti-gE results and met timing and other conditions. The registry’s description is truncated after referring to prohibited concomitant medication. The full eligibility and analysis criteria are therefore not reported in the registry record. For secondary endpoints, the posted analysis populations vary by outcome; the outcome-specific counts indicate that the available population is not necessarily identical across measures.

The registry does not provide a complete account of missing-data handling, exclusions after randomization, or sensitivity analyses assessing the effects of missing measurements or protocol deviations. These details matter because a per protocol analysis can exclude participants based on post-randomization events, and the resulting group comparison may differ from one based on all randomized participants. This is a general methodological concern, not evidence that exclusions biased these results. The status of interim analyses, the full statistical analysis plan, and the rationale for the analysis populations are not reported in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: transitional cell carcinoma (0.8%), iron deficiency anaemia (0.4%), anaemia (0.4%), arteriosclerosis coronary artery (0.4%), myocardial infarction (0.4%).

For serious adverse events, the registry reports 13 affected participants in the co-administration group and 6 in the control group, with 265 participants at risk in each group. It reports zero deaths in each group. These counts describe events recorded during the study; they do not by themselves establish that an event was caused by a vaccine. The registry does not provide a causal attribution for the serious-event counts in the summary figures.

The listed serious-event terms include transitional cell carcinoma, iron deficiency anaemia, anaemia, arteriosclerosis coronary artery, myocardial infarction and atrial fibrillation. The registry gives percentages for these terms, but the terms are not a substitute for the complete event listing or clinical review. The summary does not establish whether individual participants experienced more than one event, and the counts should not be added to estimate a total number of affected participants.

Other adverse events were reported for 240 participants in the co-administration group and 235 in the control group, with 265 at risk in each group. These summary counts do not indicate severity, duration or causality for each event. Safety comparisons should be interpreted in light of the study’s size, follow-up and event definitions; the registry record does not provide all details needed to assess those aspects independently.

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

The primary endpoint describes anti-gE antibody concentration after the second HZ/su dose. The sponsor reports a noninferiority ratio and the registry reports group GMC estimates with confidence intervals. Together, these statistics describe the measured immune response in the analyzed population at the stated follow-up time. They do not directly measure infection, disease severity, hospitalization or clinical protection.

A noninferiority label is meaningful only in the context of a prespecified margin, an understood ratio orientation and a suitable analysis population and method. Those details are not all reported in the registry record. The sponsor’s analysis can be stated as posted, but the available registry information is not enough to independently verify the criterion underlying its noninferiority interpretation. The group GMCs are descriptive summaries and should not be treated as a substitute for that formal comparison.

The secondary results address other immune measures and safety outcomes. They can add context about measured responses and recorded events, but they do not establish that the vaccines prevent illness or that an antibody response persists beyond the measured timepoints. Unadjusted secondary comparisons also carry less confirmatory weight when the multiplicity strategy is not reported.

The findings apply to the study’s recorded population, regimens and assessment times. The design compares co-administration on Day 1 with RSVPreF3 OA on Day 31, while both groups receive HZ/su on Day 1 and Day 61. It does not compare every possible dosing schedule, and the registry does not provide results for all outcomes in a form that supports a two-arm comparison. The posted data should therefore be understood as evidence about these particular measured outcomes and schedules, with uncertainty and reporting limitations, rather than a general statement about all people, settings or clinical outcomes.

14. Why This Trial Matters Statistically

This trial raises a practical statistical question about comparing an immune response when two vaccines are given at the same visit versus at separate visits. Randomization and a parallel-group design provide a framework for comparing those schedules, while the primary antibody endpoint gives a defined, measurable response at a stated time after the second HZ/su dose. The study also measures responses to RSV-A and RSV-B and records safety outcomes, so the statistical interpretation must keep distinct outcomes and targets separate.

The primary analysis illustrates why an endpoint estimate and a formal comparison are not interchangeable. The registry reports adjusted GMCs for both groups and a sponsor-labeled noninferiority ratio, but the margin, ratio orientation and model details are absent. Those are not minor presentation details: they are needed to understand what the ratio compares and what criterion supports the noninferiority interpretation. This makes the record useful for describing the estimates while limiting independent verification of the sponsor’s conclusion.

The trial also illustrates the difference between confirmatory and supportive evidence. Many secondary immune and safety outcomes can help characterize the study, but unadjusted comparisons across multiple endpoints should not be treated as repeated independent confirmation. Planning illustrations based on observed effects can inform hypothetical future designs, but they cannot establish the power of this completed study or explain the original sample-size choice.

For clinical researchers and biostatisticians, the central lesson is to connect each estimate to its population, timing, measurement and analysis method. A precise-looking antibody estimate is still an immune-response measure, not a clinical endpoint, and an incomplete registry description leaves some analytical choices unresolved. These distinctions are important when assessing what the posted evidence can and cannot support.

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.

Several study-specific limitations affect interpretation of the posted results. The trial is open-label, so participants and study personnel knew the assigned schedule. The primary endpoint is a laboratory antibody measure, and the registry does not report a clinical disease endpoint as the primary outcome. The primary analysis is described as per protocol rather than as an all-randomized-participant analysis, and the full criteria for inclusion in that population are not available because the registry description ends mid-criterion.

The registry does not report the primary adjustment model, its covariates, the ratio orientation or the noninferiority margin. Those omissions limit independent appraisal of the sponsor’s primary analysis. It also does not report the full statistical analysis plan, multiplicity handling, missing-data methods, interim analyses or the sample-size justification. These details are important for judging how the analysis was planned and whether the estimates and uncertainty measures follow the intended protocol.

The posted analysis counts differ by endpoint, reflecting outcome-specific populations and data availability. The record does not provide a complete account of why participants were excluded from each analysis or how missing measurements were addressed. Some outcomes are not reported in a form that supports a two-arm comparison, so they cannot be given the same comparative interpretation as the primary endpoint or the recalculated secondary outcomes.

Finally, the study evaluates particular vaccine schedules and measures responses at defined timepoints. The registry summaries do not establish longer-term persistence or clinical protection. Safety counts alone do not establish causality, and the registry summary does not supply a complete narrative of event assessment. These limits apply to interpretation of the record and do not demonstrate that a specific bias or safety issue occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study on Safety and Immune Response of Investigational RSV OA Vaccine in Combination With Herpes Zoster Vaccine in Healthy Adults — NCT05966090.
• Registry record last updated 2025-04-01; status last verified 2025-03.
• Results first posted 2025-04-01.
• 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.

19. Record Summary

NCT05966090 is a completed, Phase III, randomized, controlled, open-label, parallel-group, multi-country study sponsored by GlaxoSmithKline. It enrolled 530 healthy adults aged 50 years and older. The co-administration group received RSVPreF3 OA and HZ/su on Day 1; the control group received HZ/su on Day 1 and RSVPreF3 OA on Day 31. Both groups received a second HZ/su dose on Day 61.

The primary outcome was adjusted anti-gE GMC at 1 month after the second HZ/su dose, Day 91. The registry reports group estimates and a sponsor-labeled noninferiority ratio, but does not report the ratio orientation, model or margin. Secondary outcomes cover additional immune responses and safety. The registry record does not report a complete statistical analysis plan, multiplicity approach, missing-data methods or sample-size justification, limiting independent assessment of several analytical choices.