Study to Evaluate the Safety, Tolerability, and Antiviral Activity of Selgantolimod (Formerly GS-9688) in Viremic Adult Participants With Chronic Hepatitis B (CHB) Who Are Not Currently on Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety, Tolerability, and Antiviral Activity of Selgantolimod (Formerly GS-9688) in Viremic Adult Participants With Chronic Hepatitis B (CHB) Who Are Not Currently on Treatment (NCT03615066), a randomized phase 2 study. The primary outcome is Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24.

2. Clinical Question

The primary endpoint was a threshold outcome: it counted whether participants reached the stated decline, rather than describing the average change in qHBsAg. The posted results report 0.0% for each of the three groups. The registry also reports risk differences of 0.0 for both selgantolimod groups compared with placebo plus TAF.

This is a question about the observed Week 24 endpoint in a phase 2 trial, not a broad assessment of all possible effects or outcomes. The registry record describes safety and tolerability as primary objectives as well as antiviral activity, but the posted primary efficacy outcome addressed the qHBsAg threshold. Other posted outcomes include qHBsAg changes and threshold declines at other weeks; those address related but distinct questions.

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter phase 2 study sponsored by Gilead Sciences. It enrolled 67 participants. The registry lists the study as completed, with a start date of 2018-08-28 and primary completion date of 2019-12-12.

Participants with HBeAg-positive or HBeAg-negative chronic hepatitis B who were not currently on oral antiviral treatment were assigned to one of three groups: selgantolimod 3 mg plus TAF, selgantolimod 1.5 mg plus TAF, or placebo plus TAF. The arm descriptions specify TAF 25 mg once daily for 24 weeks, with weekly selgantolimod or placebo dosing for 24 doses. The descriptions also refer to treatment after the 24th dose, but the complete continuation details are not reported in the registry record.

Double masking and placebo control are design features intended to reduce the influence of treatment knowledge on participants and study conduct. Randomization is intended to support comparable groups on average, although it cannot ensure exact balance in a study of this size. These are general design principles; they do not establish how well masking was maintained or whether all randomization procedures were followed, which are not reported in the registry record.

The primary endpoint analysis population is defined as randomized participants who took at least 1 dose of study drug. The reported group sizes for the primary endpoint are 26 for selgantolimod 3 mg plus TAF, 28 for selgantolimod 1.5 mg plus TAF, and 13 for placebo plus TAF. The registry record does not report details of the allocation sequence, concealment procedures, or the planned statistical analysis beyond the endpoint and population descriptions.

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: 96 participants were screened.

Main Study

Reasons for not completing this period:

Treatment-free Follow-up (TFFU) Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set included all randomized participants who took at least 1 dose of the study drug.

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 took at least 1 dose of the study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24, measured over Baseline, Week 24.

The primary endpoint is the percentage of participants whose serum quantitative hepatitis B surface antigen (qHBsAg) declined by at least 1 log10 IU/mL from baseline at Week 24. It is a binary endpoint: each participant either meets the stated decline threshold or does not. The percentage therefore describes how often that threshold was reached in each group, rather than the typical size of change across all participants.

A threshold endpoint can make a specified degree of change easy to interpret as a participant-level outcome. It also compresses information: participants just below the threshold and participants with no decline both count as not reaching it, while any participant reaching the threshold counts as an event regardless of how much further the value declined. This is a general feature of dichotomizing a continuous measure, not a finding specific to this trial.

The endpoint uses qHBsAg measured at baseline and Week 24. The registry lists the unit as percentage of participants and defines the primary analysis population as randomized participants who took at least 1 dose of study drug. It does not report further details about measurement procedures, handling of values below assay limits, or how missing Week 24 measurements were classified.

The posted values are 0.0% in each group. These results describe the recorded endpoint in this trial; they do not by themselves answer questions about other qHBsAg changes, other time points, or clinical outcomes not represented by this measure.

7. Results Posted in the Registry

• Selgantolimod 3 mg + TAF: 0.0% (0/26) versus 0.0% (0/13) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• Selgantolimod 1.5 mg + TAF: 0.0% (0/28) versus 0.0% (0/13) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Serum qHBsAg at Week 4

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Selgantolimod 3 mg + TAF: mean -0.04 versus -0.02 on control; difference -0.02 (95% CI -0.09 to 0.05), standardized effect d = -0.15; z-test p = 0.577.
  • Selgantolimod 1.5 mg + TAF: mean -0.01 versus -0.02 on control; difference 0.01 (95% CI -0.04 to 0.06), standardized effect d = 0.13; z-test p = 0.675.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Selgantolimod 3 mg + TAF and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Selgantolimod 1.5 mg + TAF and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Serum qHBsAg at Week 8

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Selgantolimod 3 mg + TAF: mean -0.04 versus 0.00 on control; difference -0.04 (95% CI -0.12 to 0.04), standardized effect d = -0.29; z-test p = 0.328.
  • Selgantolimod 1.5 mg + TAF: mean -0.05 versus 0.00 on control; difference -0.05 (95% CI -0.11 to 0.01), standardized effect d = -0.45; z-test p = 0.126.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Selgantolimod 3 mg + TAF and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Selgantolimod 1.5 mg + TAF and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in Serum qHBsAg at Week 12

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Selgantolimod 3 mg + TAF: mean -0.04 versus 0.01 on control; difference -0.05 (95% CI -0.14 to 0.04), standardized effect d = -0.34; z-test p = 0.254.
  • Selgantolimod 1.5 mg + TAF: mean -0.05 versus 0.01 on control; difference -0.06 (95% CI -0.13 to 0.01), standardized effect d = -0.57; z-test p = 0.090.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Selgantolimod 3 mg + TAF and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Selgantolimod 1.5 mg + TAF and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the qHBsAg assessment beyond the Week 24 threshold in the primary endpoint. They include threshold declines at Weeks 4, 8, 12, and 48, as well as mean changes from baseline at Weeks 4, 8, 12, and 24. The available numerical continuous comparisons cover Weeks 4, 8, and 12. They describe a time-dependent pattern rather than a consistent, clearly separated difference between each selgantolimod group and placebo plus TAF.

This broader set of outcomes is related to the primary question, but it is not interchangeable with it. A mean change uses information from the size of changes across participants, whereas a threshold outcome counts only whether a specified decline was reached. A mean pattern at an earlier visit cannot establish that the Week 24 threshold was met, and the primary result does not capture every possible continuous change. The posted primary endpoint was zero in all groups, while the secondary outcomes offer a different and incomplete view of qHBsAg over time.

The secondary comparisons are recalculated and unadjusted; the registry lists no reported analyses. When many outcomes or time points are examined, the chance of at least one apparently unusual result can increase even if there is no true difference. Adjustment or a prespecified hierarchy can help address that issue, but the registry record does not report a multiplicity strategy. Accordingly, isolated unadjusted secondary findings carry less weight than a prespecified, sponsor-reported analysis that accounts for the full set of comparisons.

The registry lists 28 posted secondary outcomes, but the record does not provide a full set of numerical summaries in the analysis details. This limits interpretation of the overall pattern. The secondary results are best viewed as exploratory context around the primary endpoint rather than independent confirmation of a treatment effect.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4
• Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8
• Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12
• Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48
• Change From Baseline in Serum qHBsAg at Week 4
• Change From Baseline in Serum qHBsAg at Week 8
• Change From Baseline in Serum qHBsAg at Week 12
• Change From Baseline in Serum qHBsAg at Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

What does the endpoint compare?

The primary endpoint is a proportion: the number of participants meeting the qHBsAg decline threshold relative to the number evaluated in a group. A risk difference expresses the difference between two such proportions, in the same percentage-point scale when proportions are expressed as percentages. A value of 0.0 means that the observed group proportions are equal. This is a general explanation of the measure. In this trial, the posted risk differences are 0.0 because the reported percentages are 0.0 in both groups being compared.

A risk difference is an absolute contrast, not a relative ratio. It answers how far apart the observed event proportions are, rather than how many times larger one is than another. When no events are recorded in either group, the observed risk difference is zero. That point estimate does not establish that the underlying event risks are exactly equal.

Why can zero events make uncertainty hard to assess?

For an event outcome, the observed proportion is determined by both the event count and the number evaluated. When an event count is zero, common large-sample calculations can encounter boundary problems: the estimated event rate is at the edge of the possible range. A simple interval for the difference may consequently have no visible width, even though the data remain compatible with uncertainty about the true rates. Other interval methods can express that uncertainty differently. This is a general statistical issue with sparse binary data. The registry record does not identify the method used for its primary interval, so the posted 0.0-to-0.0 intervals should not be interpreted as showing no uncertainty.

How do the continuous secondary outcomes differ?

The secondary qHBsAg change outcomes report group means in log10 IU/mL and standard deviations. A mean describes the average observed change in a group; a standard deviation describes how dispersed individual changes are around that mean. A mean difference compares the two group averages. The registry lists recalculated, unadjusted mean differences for the reported Week 4, Week 8, and Week 12 comparisons. These are simple comparisons from posted summary statistics, not reported sponsor analyses. The registry record does not report adjusted analyses for these outcomes.

Standard deviations are not confidence intervals. They describe variation among participant measurements, while a confidence interval describes uncertainty in an estimated quantity. With fewer observations or greater variation, an estimate generally has less precision. Over-dispersion is a general concern when data vary more than a model assumes: standard errors and resulting intervals can then be too small if that extra variation is ignored. The registry’s secondary continuous outcomes include standard deviations, but the statistical model used by the sponsor is not reported.

How should p-values and intervals be read?

A p-value, in general, describes how compatible data are with a specified null model under the assumptions of a statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The secondary p-values listed in the record are unadjusted recalculations. The primary endpoint has no p-value reported. The registry record does not report the sponsor’s test, a prespecified significance threshold for outcome comparisons, or a multiplicity adjustment plan.

A confidence interval gives a range of values compatible with the data and the method’s assumptions at its stated confidence level. It is not a guarantee that the true value lies in that range. Intervals for the recalculated continuous comparisons include zero, indicating that those unadjusted summaries do not clearly distinguish the group mean changes from no difference under the interval calculations. Their interpretation remains limited by the small group sizes, repeated outcomes, and lack of a reported sponsor analysis.

What do the planning illustrations mean?

The sample-size illustrations use observed effects from the continuous secondary comparisons. They assume a two-sided significance level of 0.05, equal allocation between two groups, and a normal approximation. The estimates describe participants per arm for 80% or 90% power if the effect to detect is the stated fraction of the observed effect. They are planning illustrations, not the trial’s design justification and not observed power. A calculation based on an effect observed in a small study can be unstable, and it should not be treated as evidence that the study had a particular probability of detecting its true effect. These illustrations do not provide a power calculation for the primary binary endpoint.

The registry record does not report the trial’s original sample-size justification, interim analyses, or a detailed statistical analysis plan. Those omissions mean that the recalculated summaries and planning illustrations cannot substitute for the sponsor’s prespecified methods.

11. Confidence Intervals and Precision

Precision concerns how narrowly an estimate is determined by the data and statistical method. For a group difference, a confidence interval displays a range of values compatible with the estimate under the method’s assumptions. A narrow interval often indicates greater precision, while a wide interval indicates that a range of effects remains compatible with the data. These are general interpretations; an interval is not a guarantee about the true value.

For the primary risk differences, the registry reports estimates of 0.0 with intervals from 0.0 to 0.0. Because no participants in any group met the threshold, these zero-width intervals should not be taken to mean the underlying difference is known exactly. Sparse binary outcomes can cause simple calculations to collapse at the boundary, obscuring uncertainty about event rates. The registry record does not identify the primary interval method or report an alternative analysis.

The recalculated intervals for the continuous qHBsAg comparisons at Week 4, Week 8, and Week 12 include zero. Those intervals reflect uncertainty in group mean differences as calculated from the posted summary statistics. The estimates are based on relatively small endpoint-specific groups, and the observed standard deviations show that participant changes varied around the group means. No sponsor-reported analyses are listed for these comparisons, so the recalculated intervals should be read as descriptive, unadjusted summaries rather than as a substitute for the trial’s planned analysis.

The record does not report confidence intervals for every listed secondary outcome. It also does not report adjustments for the several outcome measures and time points. The interval evidence therefore addresses individual comparisons under their calculation assumptions; it does not account for the uncertainty introduced by considering many outcomes.

12. Multiplicity, Missing Data and Analysis Populations

The primary analysis population is defined in the registry as the Full Analysis Set, including randomized participants who took at least 1 dose of study drug. The posted primary endpoint group sizes are 26, 28, and 13. This definition helps clarify who was intended to contribute to the primary result, but it does not describe how participants with missing Week 24 measurements were handled.

Missing-data procedures are not reported in the registry record. It does not state whether missing endpoint values were imputed, treated as not meeting the threshold, excluded from a particular calculation, or addressed using another approach. The record also does not explain reasons for missing observations. Without those details, the endpoint estimates cannot be fully assessed for sensitivity to missing data.

The registry identifies several related outcomes across multiple weeks, including threshold declines and mean changes in qHBsAg. Repeated testing across outcomes and time points creates a multiplicity concern: even when all underlying effects are null, the chance of finding at least one apparently notable result can rise as more comparisons are considered. This is a general statistical principle. The registry record does not report a plan for controlling multiplicity, an outcome hierarchy, or adjusted p-values.

The registry lists no reported analyses. The continuous comparisons and associated p-values available in the record are recalculations from posted summary statistics and are unadjusted. They should not be presented as the sponsor’s prespecified inferential results. The analysis population and missing-data methods for the secondary outcomes are not reported in the registry record.

The primary result is therefore interpretable as the posted percentage in the stated analysis population, but key details needed to evaluate robustness are unavailable. These include the missing-data approach, analysis model, multiplicity handling, and any sensitivity analyses. The record also does not report interim analyses or the original sample-size justification.

13. 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: limb injury (3.8%).

The registry reports serious adverse events in the three groups as follows: 1 participant in the selgantolimod 3 mg plus TAF group, 0 in the selgantolimod 1.5 mg plus TAF group, and 0 in the placebo plus TAF group. It lists 26, 28, and 13 participants at risk, respectively. Deaths are reported as 0 in each group. The top serious adverse event term listed is limb injury at 3.8%; the registry record does not provide further context for that term in the posted details.

The record also reports other adverse events affecting 21 participants in the 3 mg group, 15 in the 1.5 mg group, and 10 in the placebo group. These counts are not the same as serious adverse event counts. The registry’s categories should be kept distinct when reading the safety results.

These figures describe events recorded in the study groups; they do not establish that an event was caused by a study drug. The record does not provide the full event definitions, exposure-adjusted rates, event timing, severity details, or a sponsor’s comparative safety analysis. With the group sizes reported, the counts are descriptive and do not alone establish whether safety differs between groups.

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

The primary result answers a narrow question: in this trial’s Full Analysis Set, what percentage in each group had at least a 1 log10 IU/mL decline in qHBsAg by Week 24? The posted percentage was 0.0% in each group. The reported risk differences were also 0.0. These data show no observed separation on this particular threshold outcome.

That result does not establish that the treatments have identical effects. No events were recorded for the threshold, and the reported zero-width intervals do not capture the uncertainty that can remain with sparse binary data. The group sizes were limited, and the registry does not report a sponsor analysis or primary p-value. Absence of an observed event is not proof that the underlying event probability is zero.

The result also does not show that qHBsAg did not change at all for any participant. A threshold outcome reduces a range of continuous measurements to whether a participant crossed a cutoff. The registry separately records mean qHBsAg changes at earlier weeks, which address a different aspect of the measurements. Nor does the primary endpoint establish effects on outcomes that were not reported in the record.

The secondary comparisons are unadjusted recalculations and should be interpreted cautiously because several outcomes and time points are considered. The registry does not report methods for missing data, multiplicity control, or a complete analysis plan. Those limits make the posted results useful as a description of recorded observations, but they constrain stronger claims about the size, precision, or consistency of treatment differences.

Overall, the registry record supports a descriptive conclusion about the observed Week 24 threshold result: no participant in any group was recorded as meeting it. It does not support claims of equivalence, definitive absence of an effect, or a conclusion about clinical benefit. Such questions require evidence and analyses beyond the posted endpoint summaries.

15. Why This Trial Matters Statistically

This trial illustrates how an endpoint’s definition shapes the statistical question. The primary outcome is a threshold-based percentage, while the secondary qHBsAg outcomes include mean changes. Those measures can summarize different features of the same biomarker, and a result on one should not automatically be treated as a result on the other.

It also demonstrates a limitation of zero-event comparisons. Identical observed percentages can yield a zero risk difference, yet the amount of information about the underlying risks may still be limited. A zero-width interval in this setting can reflect a calculation method at the boundary rather than genuine certainty. Understanding that distinction is important when reading trial summaries with sparse binary endpoints.

The design includes randomization, double masking, a placebo comparison, and a parallel-group structure. These design features support a controlled comparison in principle. At the same time, the primary endpoint groups are modest in size, and the registry record does not report the sponsor’s analysis methods, missing-data procedures, multiplicity approach, or sample-size justification. The posted summaries therefore call for careful separation of observed data from stronger inferential claims.

The secondary results and planning illustrations further show why exploratory calculations should be kept in context. Recalculated unadjusted comparisons can help describe patterns, but they are not substitutes for prespecified analyses. Sample-size illustrations based on observed effects are planning aids, not evidence of the study’s observed power or a record of the original design rationale.

16. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several limitations specific to this trial affect interpretation of the posted results. The primary endpoint has no recorded events in any group, and the registry reports a zero risk difference with a zero-width interval for each comparison. Such a result is not evidence that the underlying risks are known exactly. The record does not specify the interval method, and the primary comparison has no reported p-value or sponsor analysis.

The registry record does not report the original sample-size justification, so it is not possible to assess the assumptions that guided enrollment. It also does not report a detailed analysis plan, interim analyses, or sponsor-reported efficacy analyses. The planning illustrations use observed effects from continuous secondary outcomes and should not be treated as the trial’s design calculation.

Missing-data handling is not reported. The record does not explain whether all randomized participants had Week 24 measurements or how unavailable measurements were treated. The primary population is defined, but the methods for applying that definition to endpoint data are not described in further detail. Analysis populations for the secondary outcomes are also not reported.

Multiplicity is another limitation: the record lists multiple qHBsAg outcomes over several time points, but no adjustment strategy or outcome hierarchy is reported. The available secondary comparisons are unadjusted recalculations rather than reported sponsor analyses. Finally, the posted safety summaries are counts and do not provide detailed event timing, exposure-adjusted rates, or comparative analyses. These limitations restrict conclusions about precision, robustness, and consistency across outcomes.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety, Tolerability, and Antiviral Activity of Selgantolimod (Formerly GS-9688) in Viremic Adult Participants With Chronic Hepatitis B (CHB) Who Are Not Currently on Treatment — NCT03615066.
• Registry record last updated 2022-05-10; status last verified 2022-04.
• Results first posted 2021-01-06.
• 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.

20. Record Summary

The registry record describes NCT03615066, a completed, randomized, double-blind, placebo-controlled, multicenter phase 2 study sponsored by Gilead Sciences. It enrolled adults with viremic chronic hepatitis B who were not currently on treatment and compared selgantolimod 3 mg plus TAF, selgantolimod 1.5 mg plus TAF, and placebo plus TAF.

The primary endpoint was the percentage with at least a 1 log10 IU/mL decline in serum qHBsAg from baseline at Week 24. The posted result was 0.0% in each group, with reported risk differences of 0.0. The registry defines the primary analysis population as randomized participants who took at least 1 dose of study drug.

The record includes additional qHBsAg outcomes and adverse event counts, but it does not report sponsor analyses, missing-data procedures, multiplicity handling, or a detailed statistical analysis plan. The available secondary comparisons are unadjusted recalculations and should be read as descriptive evidence.