A Study to Test GlaxoSmithKline's (GSK) Herpes Zoster (HZ) Subunit Vaccine's Long-term Immune Response in Previously Vaccinated Kidney Transplant Adults and Then to Test if 2 Additional Doses of the Vaccine Are Safe and Able to Generate an Immune Response: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test GlaxoSmithKline's (GSK) Herpes Zoster (HZ) Subunit Vaccine's Long-term Immune Response in Previously Vaccinated Kidney Transplant Adults and Then to Test if 2 Additional Doses of the Vaccine Are Safe and Able to Generate an Immune Response (NCT04176939), a na phase 3 study. The primary outcome is Anti-glycoprotein E (Anti-gE) Antibody Concentrations, as Assessed in the Long Term Follow-up (LTFU) Phase of the Current ZOSTER-073 Study.

2. Clinical Question

The study followed adults with renal transplants who had completed a two-dose herpes zoster subunit vaccine course in the earlier ZOSTER-041 study. It assessed anti-glycoprotein E antibody concentrations over the long term, before any additional vaccination in the current study, and examined safety. It also assessed immune responses and safety after some participants received additional doses.

The primary outcome concerns antibody concentrations, not the occurrence of herpes zoster. The record names additional outcomes that include cellular immune response, suspected or confirmed herpes zoster, allograft rejection, and allograft dysfunction. These outcomes address different questions and should not be treated as interchangeable measures of immune response or clinical disease.

The record describes a single-group study, not a randomized comparison. It therefore does not establish a like-for-like comparison between vaccinated and unvaccinated participants. Its focus is follow-up within a group previously vaccinated in the earlier study, with additional vaccination assessed in some participants. Numerical primary antibody results are not reported in the registry record, so the magnitude and precision of the antibody concentrations cannot be evaluated from the record.

3. Trial Design

This is a completed Phase 3, single-group study sponsored by GlaxoSmithKline. The registry lists enrollment of 68 participants, a start date of 2019-12-09, and primary completion on 2022-08-12. The intervention is the HZ/su vaccine, identified as GSK1437173A. The masking field is recorded as none, and allocation is recorded as not applicable. These design details do not describe a blinded randomized comparison.

Participants had renal transplants and had completed the two-dose HZ/su course in the earlier ZOSTER-041 study. The current study was intended to assess long-term immune response and safety up to 7 years after that original course. It also assessed immune response and safety after two additional doses administered 6 to 8 years after the original course. The arm description states that 47 participants further received one or two additional doses; the available description is incomplete, so further detail about the dose groups is not reported in the registry record.

The primary outcome was assessed at Day 1, Month 12, and Month 24 in the long-term follow-up phase, before revaccination. Other listed outcomes include gE-specific CD4 T-cell frequency; serious adverse events related to the primary vaccination in ZOSTER-041; suspected or confirmed and confirmed herpes zoster cases; and suspected or biopsy-proven allograft rejection and related dysfunction. The record lists 26 outcome measures, but that count alone does not indicate how many were analyzed or how results were handled statistically.

Because there is no randomized control group, changes over time can describe the observed course among participants followed, but they cannot isolate the effect of vaccination from other influences. Details of the planned statistical analysis, including any adjustment or interim analyses, 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: Out of the 68 participants originally enrolled in the current ZOSTER-073 study (Enrolled Set), 21 participants did not receive any revaccination doses, hence only 47 participants were vaccinated with at least one revaccination dose and included in the Exposed Set for revaccination phase in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the Per Protocol Set for analysis of persistence (LTFU phase), which included evaluable participants from the Enrolled Set with a complete vaccination course (2 doses of HZ/su vaccine) in the ZOSTER-041 study, who met the eligibility criteria and signed informed consent in the current study and for whom persistence immunogenicity results after primary vaccination course were available at the specified time points in the current study, regardless of revaccination status.

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-glycoprotein E (Anti-gE) Antibody Concentrations, as Assessed in the Long Term Follow-up (LTFU) Phase of the Current ZOSTER-073 Study, measured over At Day 1, Month 12 and Month 24 (pre-revaccination) in the current ZOSTER-073 study.

The primary endpoint is the geometric mean concentration (GMC) of anti-glycoprotein E antibodies, measured by enzyme-linked immunosorbent assay and expressed in mIU/mL. The registry specifies measurement at Day 1, Month 12, and Month 24 before revaccination during the current study. It also specifies a 95% confidence interval for the GMC.

Antibody concentration is a laboratory measure of humoral immune response. A geometric mean is used for measurements that are analyzed on a multiplicative scale, often because concentrations are skewed rather than symmetrically distributed on their original scale. In general, this approach summarizes a typical concentration while reducing the influence of very high values on the mean. The registry does not report the observed GMCs or their confidence intervals, so the actual antibody levels and their precision cannot be assessed from this record.

These measurements describe antibody response; they are not themselves counts of herpes zoster cases or proof of protection from disease. A confidence interval expresses uncertainty around an estimated quantity under the analysis assumptions. It is not a range containing most individual participants' antibody values. The rationale for choosing this endpoint and any threshold for interpreting it are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous laboratory measurement summarized as a geometric mean concentration. The registry says anti-gE antibodies were measured by ELISA and reports the unit as mIU/mL. It specifies a 95% confidence interval around the GMC. The record does not provide the numerical estimates, the precise confidence-interval procedure, or the analysis code or model.

Why use a geometric mean?

General statistical explanation: laboratory concentrations can have a right-skewed distribution, in which a small number of high measurements pull an ordinary arithmetic mean upward. A geometric mean is typically calculated by taking logarithms of the measurements, averaging on the log scale, and transforming the result back to the original scale. It is naturally interpreted on a multiplicative scale. That can be useful when relative changes are more meaningful than equal absolute changes. The registry identifies the geometric mean but does not report the distribution of values or explain the choice of summary measure.

What does a confidence interval convey?

General statistical explanation: a confidence interval represents uncertainty in an estimated population quantity under the assumptions of the statistical method. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. A 95% confidence interval is not a statement that 95% of individual participants' measurements lie inside the interval. The interval's width depends on factors such as the number of evaluable observations and variability. In this study, neither the primary GMCs nor their intervals are reported in the registry record, and the number contributing to each time point is not reported there.

How should the time points be read?

The primary measurements are listed at Day 1, Month 12, and Month 24 of the current long-term follow-up phase, before revaccination. This sequence describes scheduled observations rather than, by itself, a statistical test of change. A within-participant analysis could account for repeated observations on the same person, whereas a comparison of separate time-point summaries would not by itself convey each participant's trajectory. The registry record does not report which approach was used, whether all observations were paired, or how missing measurements were handled. It also does not report a formal test of change.

The study's broader aim included safety and immune response after additional doses, but the primary outcome specified is pre-revaccination. These are distinct analysis questions. Post-dose measurements would need their own time points, analysis populations, and summaries to estimate responses after additional vaccination. Those details are not reported in the registry record.

What can a single-group design estimate?

General statistical explanation: a single-group study can describe outcomes observed in the enrolled participants. Repeated measurements can show how a measure varies over follow-up, subject to the available observations and analysis choices. Without a concurrent randomized control group, however, a change cannot be separated cleanly from time trends, changes in health, background exposures, or other factors. A comparison within the same people can control for some stable individual characteristics, but it does not remove time-varying confounding or establish what would have happened under an alternative treatment strategy.

The registry lists allocation as not applicable and the model as single-group. It does not describe randomization between the participants who received additional doses and those who did not. Accordingly, differences between those subsets, if reported elsewhere, would not automatically be causal effects of additional vaccination. Their interpretation would depend on how participants entered each subset and on the analysis methods, details that are not reported in the registry record.

What does over-dispersion mean in general?

General statistical explanation: for event counts, over-dispersion occurs when variation is greater than a model such as a basic Poisson model expects. Ignoring it can make standard errors too small and confidence intervals too narrow. A model that allows extra variation may be appropriate for some count outcomes. The registry record does not report whether over-dispersion was assessed or which models were used for event outcomes, so it is not possible to say that it affected this study's estimates.

The record lists 26 outcome measures and no analysis count. A list of outcomes is not a substitute for a statistical analysis plan: it does not specify which outcomes were primary in each phase, which tests were planned, or how estimates would be adjusted. The planned statistical methods, including any interim analyses, are not reported in the registry record.

The record also includes a planning illustration based on an observed effect and describes assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such calculations are planning illustrations, not observed power and not evidence that this single-group study was designed with that comparison. The record's description does not change the design details: the study is listed as single-group, and its allocation is not applicable. No numerical planning results are reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 26 outcome measures, including laboratory immune measures, herpes zoster events, serious adverse events, and transplant-related outcomes. When many outcomes or time points are examined, the chance of at least one apparently unusual result can increase if each is tested separately. General statistical practice may address this through a prespecified hierarchy, adjustment, or careful emphasis on estimation rather than isolated significance tests. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or which analyses were prespecified.

The primary outcome specifies three assessment times, but no numerical GMCs, confidence intervals, or analysis results are reported in the registry record. The record lists no analyses. It therefore does not allow readers to determine which time-point comparisons, if any, were formally tested, whether adjustment was used, or how estimates were selected for reporting.

The primary population is described as the Per Protocol Set for analysis of persistence in the long-term follow-up phase, comprising evaluable participants from the enrolled set who completed the two-dose course in ZOSTER-041 and met eligibility requirements and consented. The description available in the registry record is incomplete. Counts in that analysis population, exclusions, and reasons for exclusion are not reported in the registry record.

Missing-data methods are also not reported in the registry record. It does not say how absent antibody measurements, withdrawals, or incomplete follow-up were handled, or whether any sensitivity analyses were conducted. These details matter because observed follow-up may differ from the experience of all enrolled participants if those with missing measurements differ systematically from those retained. The enrollment total should not be assumed to equal the number contributing to each endpoint or time point.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 (8.8%), kidney transplant rejection (4.4%), acute kidney injury (2.9%), anaemia (2.9%), covid-19 pneumonia (2.9%).

The registry reports serious adverse events for the HZ/su Group with 68 participants at risk and 23 affected. It separately reports other adverse events with 47 participants at risk and 43 affected. These are counts of participants, not necessarily counts of distinct events; one participant can experience more than one event. The record does not report the observation window for these figures in the information available, so they should not be treated as rates over a specific duration.

The listed serious-event terms and percentages are COVID-19, 8.8%; Kidney transplant rejection, 4.4%; Acute kidney injury, 2.9%; Anaemia, 2.9%; COVID-19 Pneumonia, 2.9%; and Pneumonia, 2.9%. These percentages are registry figures and should not be converted into event counts without additional information. The record does not establish that these events were caused by the vaccine. It also reports 7 deaths in the group, but cause and timing are not reported in the registry record.

Safety summaries describe events observed during study follow-up. They do not, by themselves, show whether an event was more common than it would have been without vaccination. Interpretation requires context about event definitions, follow-up duration, attribution, and a suitable comparison; those details are not reported in the registry record.

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

The registry record describes a study of long-term immune response and safety after an earlier two-dose HZ/su vaccination course in adults with renal transplants. It also describes assessment of immune response and safety after additional doses in some participants. This gives the study a focused descriptive role: following a selected group with prior vaccination and recording immune and safety outcomes over time.

The record does not report the numerical primary GMCs or their 95% confidence intervals. It therefore cannot show how high the anti-gE concentrations were, how they changed across the listed pre-revaccination time points, or how precisely they were estimated. Nor can the endpoint alone establish protection from herpes zoster. Antibody concentration is a laboratory measure, while clinical disease is a separate outcome.

The single-group design does not provide a randomized control group for estimating what would have occurred without prior vaccination or without additional doses. Observations among participants who received additional doses may describe their outcomes, but cannot establish a causal effect of revaccination without an appropriate comparison and analysis. The registry does not report those numerical results or the methods needed to evaluate them.

The safety figures identify participants with reported serious and other adverse events, selected event terms and percentages, and deaths. They are not evidence that the vaccine caused the listed events. They also cannot, on their own, establish comparative safety in the absence of a control group and fuller information about event timing, definitions, and attribution.

In general, a study can contribute useful descriptive information even when it does not answer a causal comparison question. Here, the design and stated outcomes indicate what was intended to be observed, but the missing numerical primary results limit interpretation of the immune response. The registry record supports no conclusion about the size or precision of that response, and no conclusion that an observed result was clinically important.

13. Why This Trial Matters Statistically

Long-term follow-up after vaccination raises statistical questions that differ from those in a short-term efficacy comparison. Antibody concentrations are repeated laboratory measurements, and their interpretation depends on how the distribution is summarized, how the same participants contribute across time, and how uncertainty is quantified. The registry specifies geometric mean concentrations and 95% confidence intervals, giving readers the intended summary framework, but does not report the numerical estimates.

The study also illustrates why design and estimand matter. A single-group follow-up can describe observed immune measures and safety events in a selected population. It cannot supply the same causal evidence as a randomized comparison. This distinction is important when interpreting follow-up after an earlier trial, particularly when some participants later receive additional doses and others do not. Without random assignment or an appropriate analytic strategy, apparent differences between subsets may reflect who received additional doses as well as the doses themselves.

The outcomes span laboratory response, clinical disease, and transplant-related events. Each outcome has a different scale and interpretation. A rise or persistence in a laboratory marker is not equivalent to fewer clinical events, and event counts do not by themselves establish attribution. Separating these outcome types prevents an immune measure from being overinterpreted as a clinical benefit.

Finally, the record highlights the importance of complete reporting. Numerical estimates, uncertainty intervals, analysis populations, missing-data methods, and multiplicity plans are needed to judge the strength and precision of findings. The endpoint definitions and design information provide useful context, but the absence of primary numerical results prevents a quantitative assessment of the long-term antibody response.

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 primary limitation for interpretation is that numerical results for the primary anti-gE GMC endpoint are not reported in the registry record. No confidence-interval values are available, and the number of participants contributing at each time point is not reported. Thus, neither effect magnitude nor precision can be evaluated from this record.

The single-group design has no randomized concurrent control group. It is appropriate for describing observations in the enrolled participants, but it cannot alone distinguish changes associated with vaccination from changes over time or other influences. Additional doses were given to some participants, but the record does not describe randomization to revaccination or provide the full details of how those receiving doses were selected.

The participant description for the persistence analysis is incomplete, and analysis-population counts and exclusions are not reported in the registry record. Missing-data handling and sensitivity analyses are also not reported. This is relevant to a follow-up study because the number and characteristics of participants with measurements may differ across visits.

The registry lists many outcomes but does not report a multiplicity approach, the planned analysis methods, or an interim-analysis plan. Numerical results for the listed clinical and transplant outcomes are not included in the information available. Safety figures lack reported observation windows and detail on event attribution in the record. The reported deaths have no accompanying cause or timing. These gaps constrain interpretation of both immune outcomes and safety, and should not be filled by assumptions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Test GlaxoSmithKline's (GSK) Herpes Zoster (HZ) Subunit Vaccine's Long-term Immune Response in Previously Vaccinated Kidney Transplant Adults and Then to Test if 2 Additional Doses of the Vaccine Are Safe and Able to Generate an Immune Response — NCT04176939.
• Registry record last updated 2025-07-18; status last verified 2025-06.
• Results first posted 2023-12-20.
• 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

NCT04176939 is a completed Phase 3, single-group study sponsored by GlaxoSmithKline. It enrolled 68 adults with renal transplants who had completed a two-dose HZ/su course in ZOSTER-041. The study assessed long-term immune response and safety, including anti-gE GMCs at Day 1, Month 12, and Month 24 before revaccination. It also assessed outcomes after additional doses; 47 participants are described as receiving one or two additional doses.

The primary endpoint is defined as an ELISA-measured geometric mean concentration with a 95% confidence interval. However, the numerical primary results are not reported in the registry record. The study has no randomized comparator, and the available record does not report the detailed statistical plan, missing-data methods, or multiplicity approach. Safety figures include 23 participants with serious adverse events among 68 at risk, 43 with other adverse events among 47 at risk, and 7 deaths; the record does not establish causation.