HEPLISAV-B® in Adults With End-Stage Renal Disease (ESRD) Undergoing Hemodialysis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for HEPLISAV-B® in Adults With End-Stage Renal Disease (ESRD) Undergoing Hemodialysis (NCT03934736), a na phase 1 study. The primary outcome is Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest.

2. Clinical Question

The study focused on adults with end-stage renal disease receiving hemodialysis, a population for whom the registry lists immunogenicity and safety as the study’s evaluation aims. The record also lists immune-response outcomes, including the percentage with an anti-HBs concentration of at least 100 mIU/mL, the serum anti-HBsAg geometric mean concentration, and the seroprotection rate. These are distinct from the primary safety endpoint.

The central interpretive question is therefore descriptive: what adverse events and immune-response outcomes were recorded among participants who received HEPLISAV-B®? Because there was no comparison arm, the study cannot establish how those outcomes differ from outcomes under another intervention or in an untreated group. The registry record does not report numerical results for the primary endpoint or the listed immune-response outcomes. The adverse-event summary does report serious-event counts and selected event terms, which can be described but do not by themselves establish that the study intervention caused an event.

3. Trial Design

This was a Phase 1, open-label, single-arm study of HEPLISAV-B® in adults with end-stage renal disease who were initiating or undergoing hemodialysis. The registry lists an enrollment of 119 and describes the study as completed. The recorded start date is 2019-04-22, and the primary completion date is 2020-10-23.

Participants received HEPLISAV-B® by intramuscular injection in the deltoid muscle. The recorded regimen was a single 0.5 mL dose at Week 0, Week 4, Week 8, and Week 16. Because the study was open-label, masking was not used. Allocation is listed as not applicable, consistent with the single-group design; the record does not describe random assignment to competing groups.

The main endpoint was a safety measure covering medically-attended adverse events, serious adverse events, and immune-mediated adverse events of special interest. Its timeframe extended from Week 0 until Week 68 or early termination. The safety population was defined as participants who received at least 1 study injection and had any post-baseline safety data. This population definition matters because a safety analysis may not include every person enrolled if eligibility for the analysis depended on receiving an injection and having subsequent safety data.

The registry also names immune-response outcomes, including anti-HBs concentration, geometric mean concentration, and seroprotection rate. The record lists 5 outcome measures, but numerical results for these outcomes are not reported in the registry record. A comparator, randomized allocation, and masking are not part of the design described in the record. Consequently, findings from this study are descriptive of the observed participants and cannot isolate treatment effects from other explanations, such as participants’ underlying health or events that might occur over time in this population.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety Population: All participants who received at least 1 study injection and who had any post-baseline safety data

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: Enrolled Population

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects Reporting Clinically Significant Adverse Events - Medically-attended Adverse Events, Serious Adverse Events, and Immune-mediated Adverse Events of Special Interest, measured over Week 0 (Visit 1) until Week 68 or early termination.

The primary endpoint measures the percentage of participants reporting specified clinically significant adverse events during the period from Week 0 until Week 68 or early termination. It includes medically-attended adverse events, serious adverse events, and immune-mediated adverse events of special interest. A medically-attended event is defined in the registry as an adverse event for which a participant sought care at a doctor’s office, clinic or study site, or emergency room, or was hospitalized. Serious adverse events are events meeting the definition of serious under FDA regulations.

Expressing an endpoint as a percentage of participants with an event is a binary-outcome approach: each participant is classified according to whether the event criterion occurred, and the summary describes the proportion meeting that criterion. This is useful for a safety endpoint because it gives a direct account of how many participants were affected within the defined analysis population. It does not convey every detail of event timing, duration, recurrence, severity, or clinical course.

The endpoint combines event categories that are important for safety surveillance, but those categories are not interchangeable. An event requiring medical attention is not necessarily serious, and an event classified as serious is not necessarily caused by the study intervention. Immune-mediated events of special interest are another defined category. The record does not report numerical primary-endpoint results or the individual category estimates. Accordingly, the registry description establishes what was intended to be measured, but does not allow the primary endpoint’s observed percentage or precision to be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a percentage-based primary endpoint, a single-arm design, and a defined safety population. The statistical concepts below explain how such information is generally interpreted; they do not fill in results or analysis details that are not reported in the registry record.

What does a percentage endpoint represent?

For a binary outcome, each participant is classified as having or not having the event under the endpoint definition. The percentage is a summary of the participants classified as having the event relative to the relevant analysis population. This kind of measure is intuitive for safety reporting, but its meaning depends on a clear event definition, a specified observation period, and a well-defined population.

The primary endpoint includes medically-attended adverse events, serious adverse events, and immune-mediated adverse events of special interest. These categories can overlap: a serious event may also require medical attention, for example. When categories are combined or reported separately, the analysis rules determine how overlap is handled. Those detailed rules and category-specific numerical results are not reported in the registry record. The endpoint description therefore tells readers what was to be assessed, but is not enough to reconstruct a complete analysis.

Why does the analysis population matter?

The stated Safety Population includes participants who received at least 1 study injection and had post-baseline safety data. This definition links the analysis to exposure and availability of follow-up safety information. It is not necessarily identical to the enrolled population, because enrollment alone does not establish that a participant received an injection or had post-baseline data. The registry record does not report how many participants were excluded from the safety population or why, so those details cannot be evaluated.

Analyses using different populations can yield different summaries if participants with missing follow-up or other eligibility differences have different outcomes. A complete account would ordinarily identify the population used for each outcome and describe participants without evaluable data. The record does not report those additional details for the primary endpoint.

What would uncertainty intervals add?

A confidence interval is a general statistical tool for describing the uncertainty around an estimate. For a percentage endpoint, it can indicate the range of values reasonably compatible with the observed data under the method’s assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. An interval is not a guarantee that the underlying value lies within its limits, and it does not address bias from study design or measurement.

No primary-endpoint estimate or confidence interval is reported in the registry record. Therefore, the precision of the primary safety result cannot be assessed from the recorded information. The listed percentages for serious-event terms are not accompanied by uncertainty intervals in the record details. A point percentage alone, even when available, would not show how much statistical uncertainty surrounds it.

Why is a comparator important?

In a controlled comparison, the outcome in one group can be considered alongside the outcome in another group, subject to the design and analysis assumptions. A randomized comparison can help balance measured and unmeasured factors on average, while masking can reduce some forms of influence on reporting and assessment. These are general design principles, not claims about an unreported analysis.

This study has a single group and no comparator. Its observed adverse events can be described, but there is no internal reference group for estimating a relative difference. The record does not report a comparative treatment effect, and no comparative conclusion can be derived from the group’s event summary alone.

How should planning calculations be read?

Sample-size calculations are planning illustrations, not observed outcomes. The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. The record does not report a trial-specific sample-size justification or the underlying calculation results in the registry record. In particular, the equal-allocation, two-arm assumptions do not describe this study’s single-arm design. Any such illustration should therefore be understood as a hypothetical planning exercise, not as evidence about the trial’s observed precision or power.

Over-dispersion is a general issue when variation in event counts or outcomes exceeds what a simple statistical model assumes. Ignoring extra variation can make uncertainty appear smaller than it is. This concern is more directly relevant to count or rate models than to a simple participant-level binary summary, but the choice of model should reflect the outcome and its distribution. The registry record does not report a statistical model for the primary endpoint, so no model-specific assumption can be attributed to the investigators.

What can be concluded from the methods record?

The record identifies a descriptive safety objective, the endpoint categories, the timeframe, and the safety population definition. It does not report the primary endpoint estimate, its interval, a detailed missing-data approach, or the statistical analysis methods. General statistical concepts can clarify what those elements would contribute, but they cannot substitute for missing results or unreported methods.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, including the primary safety endpoint and secondary immune-response outcomes. When a study examines multiple outcomes, the chance of finding at least one apparently notable result can increase if each is tested separately without an adjustment. This is the general issue of multiplicity. Whether and how it was addressed depends on the analysis plan, including which outcomes were confirmatory and how tests were ordered or adjusted. The statistical plan and any multiplicity procedure are not reported in the registry record.

The registry records 0 analyses. This means there are no analysis entries recorded in the registry information; it does not establish that no analyses were conducted. Numerical results for the primary endpoint and the named secondary outcomes are not reported in the registry record. No conclusions about statistical significance, multiplicity adjustment, or the hierarchy of outcome testing can therefore be drawn from those missing analysis details.

The primary safety population is defined as participants who received at least 1 study injection and had any post-baseline safety data. The record does not report how missing safety data were handled, whether any participants lacked evaluable data, or whether any sensitivity analyses were conducted. It also does not provide an outcome-specific analysis population for the secondary outcomes. These omissions limit assessment of whether missing observations could have affected the results and whether populations were consistent across outcomes.

Missing-data methods matter because the reason data are absent can be related to participants’ health or event experience. Different assumptions about missing outcomes can lead to different estimates. This is a general statistical concern, not evidence that missingness affected this study. The registry record does not report enough information to evaluate it.

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

Serious events with the highest arm-level rate: pneumonia (7.6%), anemia (4.2%), gastrointestinal haemorrhage (4.2%), sepsis (4.2%), cellulitis (3.4%).

The adverse-event summary lists 119 at risk and 58 affected for serious events, and records 14 deaths. These are counts in the registry summary, not a comparison between treatment groups. Because this was a single-arm study, the figures describe events recorded in the study group and do not show whether event frequency differed from a control condition.

The registry also lists selected serious-event terms and their percentages: pneumonia at 7.6%, anemia at 4.2%, gastrointestinal haemorrhage at 4.2%, sepsis at 4.2%, cellulitis at 3.4%, and corona virus infection at 3.4%. The listed terms do not provide a complete account of each participant’s clinical course, event timing, recurrence, or relationship to the study intervention. The registry record does not report a causal assessment alongside these figures.

Serious adverse events are defined by regulatory seriousness criteria, which are distinct from whether an event was caused by treatment. Likewise, the occurrence of a death during a study does not by itself establish treatment causation. The summary does not provide the context needed to attribute the deaths or serious events to HEPLISAV-B®. These counts should be read as descriptive safety information, not as causal or comparative estimates.

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

The study’s design and registry information establish that safety was assessed in adults with end-stage renal disease initiating or undergoing hemodialysis after receiving HEPLISAV-B®. The primary endpoint focused on medically-attended adverse events, serious adverse events, and immune-mediated adverse events of special interest during the specified follow-up period. The adverse-event summary records serious-event counts, deaths, and selected serious-event terms.

Those observations do not establish whether HEPLISAV-B® caused any particular event. Serious events and deaths can occur for many reasons, and this study had no comparator group to provide a reference for interpreting how frequently they might occur in the absence of the study intervention or under another treatment. The open-label design also does not provide masked assessment. The record does not report a numerical result for the primary endpoint, so neither its event percentage nor its statistical precision can be judged from the registry information.

The registry lists immune-response outcomes, but their numerical results are not reported in the registry record. The endpoint names alone do not establish the size, consistency, or precision of any immune response. They also do not support a comparison with another intervention.

In statistical terms, the evidence described is limited to a study design and a descriptive adverse-event summary. It can inform what was monitored and what events were recorded, but it cannot support a comparative treatment-effect estimate. It is also not enough to determine whether observed events were more or less common than expected in a similar population. That would require suitable comparative information and analysis, neither of which is reported in the registry record.

The most defensible interpretation keeps three ideas separate: events were recorded during the study; their occurrence is not equivalent to proof of causation; and the absence of reported endpoint estimates limits conclusions about the planned safety and immune-response outcomes. The registry information does not justify a treatment recommendation or a claim that the intervention does or does not work.

13. Why This Trial Matters Statistically

This study is statistically notable for examining a defined safety question in adults with end-stage renal disease undergoing hemodialysis, using an explicit safety population and follow-up timeframe. The registry distinguishes the primary safety endpoint from secondary measures of immune response. Keeping those outcome types separate helps prevent an immune-response measure from being mistaken for a safety result, or vice versa.

The study also illustrates why design affects what an estimate can mean. A single-arm study can describe the outcomes observed among participants, but it cannot make a randomized, like-for-like comparison. This matters especially for safety outcomes, which may reflect underlying illness, other care, or events that occur over time as well as any potential intervention-related effects. The absence of a comparator is therefore not a minor reporting detail; it limits causal and comparative interpretation.

Another statistical lesson is that endpoint definitions and analysis populations shape the meaning of a percentage. Here, the primary endpoint specifies event categories and a timeframe, while the Safety Population requires both exposure and post-baseline safety data. These definitions help readers understand what a reported estimate would represent. However, the registry does not report the primary endpoint estimate or its uncertainty, so the key descriptive quantity cannot be assessed.

The adverse-event summary shows the value and limits of registry reporting. Counts and selected event terms provide descriptive information, but without comparative data, causal assessment, and fuller analysis details, they cannot establish treatment attribution. The listed immune-response outcomes likewise cannot be evaluated without their numerical results.

For biostatistical interpretation, the record is a reminder that a completed study and a named endpoint do not by themselves supply an interpretable estimate. Results, precision, analysis populations, missing-data handling, and the comparison structure all contribute to the strength and scope of conclusions.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation is that numerical results for the primary endpoint are not reported in the registry record. The record therefore does not give the percentage of participants meeting the endpoint or an interval describing its precision. Numerical results for the listed immune-response outcomes are also not reported in the registry record, preventing assessment of those outcomes.

The design was open-label and single-arm, with no comparator. This limits interpretation to descriptive observations and prevents a controlled estimate of differences in safety or immune-response outcomes. The absence of masking can also matter for event reporting or assessment, particularly when the endpoint includes whether medical attention was sought. These design features do not invalidate descriptive reporting, but they narrow what the findings can establish.

The registry defines the safety population, but does not report how many participants contributed to each outcome analysis, whether any participants had missing data, or how missing observations were handled. Detailed analysis methods, confidence intervals, sensitivity analyses, and multiplicity procedures are not reported in the registry record. The record also does not provide the context needed to evaluate causality for the serious events or deaths.

The listed serious-event terms and percentages offer only a partial view of safety. The record details do not include event-level timing, recurrence, severity beyond the serious classification, or a full account of concomitant conditions and other care. These limitations are especially important in a population with end-stage renal disease undergoing hemodialysis, where the study has no comparison group to help distinguish background events from possible intervention-related events. The registry information should therefore be interpreted as a limited descriptive record rather than a complete causal or comparative analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: HEPLISAV-B® in Adults With End-Stage Renal Disease (ESRD) Undergoing Hemodialysis — NCT03934736.
• Registry record last updated 2024-08-09; status last verified 2024-08.
• Results first posted 2024-08-09.
• 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

NCT03934736 is a completed Phase 1, open-label, single-arm study of HEPLISAV-B® in adults with end-stage renal disease initiating or undergoing hemodialysis. The registry lists an enrollment of 119, a start date of 2019-04-22, and a primary completion date of 2020-10-23. Participants were scheduled to receive a 0.5 mL intramuscular dose at Week 0, Week 4, Week 8, and Week 16.

The primary outcome concerned medically-attended adverse events, serious adverse events, and immune-mediated adverse events of special interest through Week 68 or early termination. The registry defines the Safety Population as participants who received at least 1 study injection and had post-baseline safety data. The adverse-event summary lists 58 affected for serious events and 14 deaths, along with selected serious-event terms. Numerical results for the primary endpoint and the listed immune-response outcomes are not reported in the registry record. With no comparator group, the recorded safety information is descriptive and does not establish causation or comparative effects.