Study of HBV Therapeutic Vaccines GS-2829 and GS-6779 in Healthy Participants and Participants With Chronic Hepatitis B: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of HBV Therapeutic Vaccines GS-2829 and GS-6779 in Healthy Participants and Participants With Chronic Hepatitis B (NCT05770895), a randomized phase 1 study. The primary outcome is Percentage of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs).

2. Clinical Question

In practical terms, the study records whether participants had adverse events after starting study drug and whether any event met the registry's definition of serious. That definition includes death, a life-threatening situation, inpatient hospitalization or prolonged hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, and medically important events or reactions.

The cohorts allow safety observations to be read in the context of participant group and dosing schedule. The healthy-participant cohorts included vaccine-specific and combined vaccine schedules; the chronic-hepatitis-B cohorts involved virally suppressed participants and combined vaccine schedules. The registry record does not report a single overall treatment-versus-placebo estimate for the primary outcome, so the results should be read as cohort-level event counts rather than as one pooled comparison.

3. Trial Design

This was a Phase 1a/1b randomized, double-masked, parallel study of GS-2829 and GS-6779, described as nonreplicating arenavirus vector therapeutic vaccines. The study status is completed, and enrollment was 83. The recorded start date is 2023-04-03 and primary completion date is 2025-01-15.

Phase 1a cohorts enrolled healthy participants. The listed schedules included low-dose GS-2829 alone, low-dose GS-6779 alone, low-dose use of both vaccines, and high-dose use of both vaccines. The combined schedules included two-cycle and three-cycle cohorts. Placebo groups are listed for healthy participants.

Phase 1b cohorts enrolled virally suppressed participants with chronic hepatitis B. These cohorts evaluated combined low-dose or high-dose schedules with two cycles, and a high-dose schedule with three cycles. A placebo group is also listed for virally suppressed participants with chronic hepatitis B. The registry describes intramuscular injections on specified study days; the schedules differ by cohort and vaccine.

Although the study is described as randomized and double-masked, the registry record does not report the randomization method, allocation ratio, masking procedures, or whether participants, clinicians, and outcome assessors were masked. It also does not report the planned sample-size justification or how cohort sizes were selected. The recorded enrollment is not a statement about the number of participants included in each particular analysis; the primary outcome says that participants in the Safety Analysis Set were analyzed.

The primary follow-up began on the first dose date and continued to the end of study, described as follow-up up to 24 weeks after the last dose. The maximum study day stated varies by cohort: up to Day 225 for cohorts 1 and 2, Day 253 for cohorts 3, 4, 5, and 6, and Day 309 for cohorts 7 and 8. These different observation windows matter when comparing event counts across cohorts, because the time available to record an event is not identical.

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: 148 participants (114 in Phase 1a and 34 in Phase 1b) were screened.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in the Safety Analysis Set were analyzed.

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: The Safety Analysis Set included all participants who received at least 1 dose of study drug.

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), measured over First dose date to end of study (followed up to 24 weeks post last dose (up to Day 225 [cohorts 1, 2], Day 253 [cohorts 3, 4, 5, 6], and Day 309 [cohorts 7 and 8]).

The primary endpoint is the percentage of participants with treatment-emergent adverse events and serious adverse events. A treatment-emergent adverse event is defined as an adverse event that starts on or after the study drug start date, or an event that leads to premature discontinuation of study drug. The timeframe begins at the first dose and continues through the end of study follow-up.

The endpoint is used to describe safety and tolerability during exposure and follow-up. Reporting the percentage of participants with an event gives a participant-level summary: each participant is counted according to whether an event occurred, rather than by the total number of event episodes. Serious adverse events are separately important because the registry definition classifies events by consequences or medical importance, including death, life-threatening situations, hospitalization, significant disability, congenital anomalies, and medically important events or reactions.

The registry reports adverse-event counts by cohort, but does not report a single combined estimate or a formal comparative analysis for this endpoint. A safety percentage is descriptive and should be interpreted alongside cohort size, follow-up length, and the types of participants and schedules in each group. It does not by itself establish whether an event was caused by a vaccine. The registry record does not report an attribution analysis or a statistical test for the primary safety outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either experienced a treatment-emergent adverse event during the defined period or did not. The serious adverse-event outcome similarly records whether a participant had a serious event. In general, a percentage for a binary outcome is a way to describe how common an outcome was in the group observed. It does not tell how many episodes each participant experienced, how long each event lasted, or whether treatment caused it.

What does the follow-up window mean?

The endpoint timeframe starts on the first dose date and ends at the end of study follow-up, which is described as up to 24 weeks after the last dose. The maximum study day differs by cohort. This means that the percentages are tied to each cohort's observation period. In general, a longer observation period creates more time in which an event can be noticed and recorded, so raw proportions across groups with unequal follow-up need careful interpretation. The registry does not report an adjustment for differences in follow-up duration.

What can the event counts establish?

The counts establish how many participants in each listed group had an event recorded under the registry's endpoint definitions. They do not, by themselves, estimate a causal treatment effect. A randomized design can support comparisons when the analysis is specified and reported, but the registry record does not report a primary-outcome comparison, effect estimate, confidence interval, or hypothesis test. No adjustment for cohort differences is reported either.

In general, an estimate based on a small group is uncertain: one participant's outcome can make a notable difference to the percentage. Confidence intervals are one way to communicate that uncertainty. They show a range of values compatible with the observed data under the statistical method used. No confidence intervals are reported for these adverse-event outcomes, so the precision of the percentages is not quantified in the registry record.

What is over-dispersion, and does it apply?

Over-dispersion is a general statistical issue that arises when data vary more than a model assumes. It matters, for example, when event counts are analyzed using a model that expects a particular amount of variability: underestimated variability can make uncertainty look too small. The primary results are participant-level event counts and percentages, and no count model or over-dispersion analysis is reported in the registry record. It is therefore not possible to say that a particular over-dispersion correction was used or needed.

How should planning calculations be read?

Any sample-size figures associated with the results are planning illustrations, not observed power and not evidence that the study was designed to detect a particular effect. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm. The registry record does not report that these assumptions were part of the trial's original design or sample-size justification.

The primary endpoint has several categories or time points and is not reduced to one comparison for the planning illustration. This is a reason not to interpret a single illustrative sample size as a plan for the primary safety analysis. The number enrolled, 83, is the recorded overall enrollment; it is not a substitute for an analysis-specific sample size or a precision assessment.

Randomization and masking are listed as design features, but the registry record does not report the operational details or the statistical analysis plan. It also reports no analyses in the analysis count. That absence means that formal comparisons, model choices, handling of repeated events, covariate adjustments, and analysis diagnostics cannot be described as performed. General statistical principles can explain what such methods would do, but cannot establish that they were used in this study.

10. Multiplicity, Missing Data and Analysis Populations

The trial includes multiple cohorts, vaccine schedules, dose levels, participant groups, safety outcomes, and secondary immune-response outcomes. In general, testing many outcomes or comparisons increases the chance of finding an apparently notable result by chance if each is treated as an independent confirmatory test. A multiplicity plan might specify which outcomes are primary, how comparisons are ordered, or whether statistical thresholds are adjusted. The registry identifies a primary safety outcome and two secondary T-cell-response outcomes, but a multiplicity strategy is not reported in the registry record.

Missing-data procedures are also not reported in the registry record. The record does not explain how participants with incomplete follow-up, missing measurements, or early discontinuation were handled in the analysis. The primary outcome describes a Safety Analysis Set, but membership criteria and the number analyzed in each cohort are not reported beyond the listed event denominators. It is therefore not possible to determine from the registry record whether all randomized participants were included or how missing safety information was treated.

The record does not report an intention-to-treat analysis, per-protocol analysis, sensitivity analysis, or rules for censoring participants. Those details are important for understanding whether exclusions or incomplete observation might affect the results. The endpoint's definition includes events leading to premature discontinuation of study drug, but the record does not describe how follow-up was handled after discontinuation.

These omissions do not change the reported counts, but they limit assessment of how completely the counts represent the randomized groups and how robust any comparisons would be. No formal primary-outcome analysis or multiplicity-adjusted result is reported.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lisfranc fracture (11.1%).

A serious adverse event is defined by the registry according to its consequences or medical importance, including death, a life-threatening situation, inpatient hospitalization or prolonged hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or a medically important event or reaction. This definition is distinct from simply describing an event as severe.

The serious-event counts are 0 in the listed cohorts except for the high-dose, three-cycle healthy-participant cohort, where 1 of 9 participants had a serious adverse event. The registry reports 0 deaths across all listed groups. It also lists Lisfranc fracture at 11.1% among the top serious terms. The record does not report an attribution judgment that would establish whether this event was related to a vaccine.

These numbers are descriptive and arise from small cohorts with different schedules and follow-up windows. A zero count means no serious event was recorded in that group during its observed period; it does not establish that the underlying risk is zero. Similarly, the presence of a serious event in a cohort does not by itself show that treatment caused it. Comparative estimates and confidence intervals are not reported in the registry record.

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

The posted results describe adverse events observed among participants in the listed study cohorts during follow-up. They show that other adverse events were recorded in each group and that serious adverse events were uncommon in the recorded cohort counts, with one serious event reported in the high-dose, three-cycle healthy-participant group and none reported in the other groups. No deaths are reported.

Those observations are not a formal comparison between vaccine and placebo. The registry record does not report an effect estimate, confidence interval, or statistical test for the primary outcome. Without those analyses, differences in the listed counts should not be treated as evidence that one schedule has a higher or lower underlying event risk. Cohort sizes are small, follow-up varies, and participant groups and schedules differ.

The safety outcome also cannot establish causality. An event occurring after the first dose meets the timing component of the treatment-emergent definition, but timing alone does not show that study drug caused it. The record does not report a causal attribution analysis.

The study's secondary outcomes concern HBV-specific T-cell responses, but results for those outcomes are not reported in the record. The safety counts therefore do not show whether vaccination changed immune responses, whether responses differed across dose schedules, or whether any immune response affected clinical outcomes.

Overall, the results are best read as early-phase descriptive safety observations within the studied cohorts. They can help characterize what was recorded under the study's schedules and follow-up, but they do not provide a precise estimate of event risk or a definitive comparative conclusion. This interpretation concerns the posted statistics and is not medical advice.

13. Why This Trial Matters Statistically

This study is statistically interesting because it places several distinct schedules and participant groups within one early-phase randomized, double-masked, parallel design. The healthy-participant cohorts and virally suppressed chronic-hepatitis-B cohorts are not interchangeable populations, and the schedules vary by vaccine, dose, and number of cycles. Reading results by cohort preserves those distinctions instead of obscuring them in a single pooled summary.

The primary outcome also illustrates a common feature of safety reporting: participant-level percentages are easy to interpret, but they do not capture event counts per person, duration, or time at risk. Cohorts have different follow-up limits, so descriptive percentages do not automatically provide an equal-duration comparison. The registry record does not report time-adjusted analyses or confidence intervals that would quantify uncertainty.

Small cohort sizes make transparent reporting particularly important. Counts communicate what occurred in the observed participants, while uncertainty intervals and planned comparisons would help readers judge how precisely those observations estimate broader event frequencies. Such statistical analyses are not reported in the registry record.

The study also shows why design labels alone are not enough to understand an analysis. Randomization and double masking are recorded, but the operational methods, analysis plan, missing-data procedures, and multiplicity strategy are not reported. Those details would clarify how the trial's design features were carried through to the reported results. The record supports a descriptive reading of safety observations, while leaving formal comparative and precision questions unresolved.

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.

Interpretation is limited by the small numbers in each listed cohort and the absence of confidence intervals for the primary safety outcome. The overall enrollment of 83 does not convey the precision of each cohort-specific estimate. The record does not report a formal comparison between vaccine and placebo groups, an effect estimate, or a statistical test.

Follow-up duration varies by cohort, with different maximum study days. No time-adjusted event analysis is reported. Participant characteristics beyond the distinction between healthy participants and virally suppressed participants with chronic hepatitis B are not described in these results. The record also does not report detailed randomization or masking procedures.

The Safety Analysis Set is named, but its membership rules and analysis counts are not reported. Missing-data handling, discontinuation follow-up, sensitivity analyses, and multiplicity procedures are not reported in the registry record. Although the primary endpoint defines treatment-emergent events, no causal attribution results are provided. Results for the listed secondary immune-response outcomes are not included in the record.

These limitations mean the reported event counts are most useful as descriptions of what occurred in the study cohorts. They do not quantify comparative safety precisely or establish causation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of HBV Therapeutic Vaccines GS-2829 and GS-6779 in Healthy Participants and Participants With Chronic Hepatitis B — NCT05770895.
• Registry record last updated 2026-01-23; status last verified 2026-01.
• Results first posted 2026-01-23.
• 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

The registry record describes a completed Phase 1a/1b randomized, double-masked, parallel study of GS-2829 and GS-6779 in healthy participants and virally suppressed participants with chronic hepatitis B. Enrollment was 83. Cohorts varied by participant group, vaccine schedule, dose level, and number of cycles; placebo groups are also listed.

The primary outcome was the percentage of participants with treatment-emergent adverse events and serious adverse events from the first dose through the end of follow-up. Other adverse events were recorded in each listed group. One serious adverse event was reported in the high-dose, three-cycle healthy-participant cohort, and deaths were reported as 0 in all groups.

The registry record does not report a formal comparative analysis, confidence intervals, detailed missing-data methods, multiplicity procedures, or results for the secondary immune-response outcomes. The findings are therefore descriptive safety observations rather than precise comparative estimates.