Efficacy, Safety and Tolerability of VS-01 in Adult Patients With Acute-on-Chronic Liver Failure and Ascites (UNVEIL-IT)®: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy, Safety and Tolerability of VS-01 in Adult Patients With Acute-on-Chronic Liver Failure and Ascites (UNVEIL-IT)® (NCT05900050), a randomized phase 2 study. The primary outcome is Chronic Liver Failure Consortium (CLIF-C) ACLF Score at Day 7.

2. Clinical Question

The clinical question is therefore framed around the Day 7 score under the two assigned care strategies, with the score serving as a measure related to organ failure and mortality risk. The posted summaries do not establish whether the observed group values represent a reliable treatment contrast. The small number of available observations, especially in the control group, makes the descriptive comparison imprecise. The registry record does not report a formal inferential result for this endpoint.

3. Trial Design

UNVEIL-IT is a Phase 2a, randomized, controlled, multicenter, open-label, parallel-group proof-of-concept study. It compared VS-01 added to standard of care with standard of care alone in adults with acute-on-chronic liver failure. The intervention is described as an intraperitoneal liposomal formulation. The registry record identifies random allocation and no masking; further details about the randomization procedure, allocation concealment, or stratification are not reported in the registry record.

The registry record reports an enrollment of 15. The primary endpoint is the CLIF-C ACLF score at Day 7, summarized as a mean and standard deviation. The endpoint population is described as all randomized participants, with only participants who had available data included in this analysis. The posted endpoint summaries include 5 active-treatment participants and 2 control participants. The record does not explain why the primary endpoint data were unavailable for other participants, nor does it report an imputation procedure.

The listed study dates are a start date of 2023-07-02 and a primary completion date of 2025-10-15. The status is terminated. The registry record does not report a reason for termination. The study's proof-of-concept framing is relevant to interpretation: the posted group summaries are descriptive and do not amount to a definitive estimate of a treatment effect.

Secondary outcomes include death counts through Day 90 and Day 28, time to death through Day 90, ACLF resolution and time to resolution through Day 28, at least one ACLF grade regression and time to that regression through Day 28, and time to transplant or death through Day 90. The record reports 9 secondary outcome measures, but no analysis results for those measures are included in the registry record. The registry record does not report a detailed statistical analysis plan, a sample-size justification, or information about interim analyses.

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: The total duration of the trial for each participant was up to 94 days. The screening period was up to 4 days, and participants were followed from Day 1 up to Day 90. The trial was discontinued prematurely at the Sponsor's decision.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS: All randomized participants. Only participants with available data were included in this analysis.

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: Full Analysis Set (FAS): All randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Chronic Liver Failure Consortium (CLIF-C) ACLF Score at Day 7, measured over Day 7.

The primary endpoint is the Chronic Liver Failure Consortium (CLIF-C) ACLF score at Day 7. It is derived from the CLIF-C organ failure score and incorporates the organ-failure score, age, and white blood cell count according to the formula stated in the registry record. The score ranges from 0 to 100, with higher values indicating greater mortality risk. It is a continuous measure, so the posted results report a mean and standard deviation for each group.

A Day 7 score offers a defined point after randomization at which the groups can be described on a common measure of illness severity. The score is intended to summarize information related to organ failure and mortality risk; it is not itself a count of deaths or a direct measure of survival. The registry record also lists mortality and clinical-status outcomes as secondary outcomes, including deaths and time-to-event measures.

The endpoint's interpretation depends on both the score values and the amount of data contributing to them. The active group mean is 50.85, with standard deviation 15.55, based on 5 participants with available data. The control mean is 39.87, with standard deviation 6.356, based on 2 participants with available data. Because the score is higher when mortality risk is greater, these observed means are interpretable in that direction descriptively. They do not, by themselves, establish a group-level effect or a causal conclusion. A formal comparison and its uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous, and its group summaries are expressed as means and standard deviations. A mean describes the arithmetic center of observed values; a standard deviation describes how dispersed those values are around the mean. The mean and standard deviation are descriptive statistics. They do not, by themselves, quantify the uncertainty in a difference between groups, and they do not show whether an observed difference is compatible with chance variation under a specified model.

What does the standard deviation describe?

In general, a standard deviation describes variation among individual observations in a group. It is not the same as a standard error or a confidence interval. A confidence interval, in general, gives a range of values compatible with the data under a statistical method and its assumptions. No confidence interval for the primary comparison is reported in the registry record. The standard deviations are 15.55 in the active group and 6.356 in the control group, but the small numbers of observations mean those estimates of within-group variability are themselves based on limited data.

Why is a formal comparison not available?

The posted endpoint results identify the two-arm continuous comparison as not estimable. The registry record therefore does not support reporting a formal test or comparative estimate for this endpoint. It would be inappropriate to substitute an independently calculated comparison and present it as the sponsor's analysis. The record does not report a p-value, confidence interval, or adjusted treatment estimate for the Day 7 score. The group means can still be described, but they do not answer the inferential question on their own.

What would an inferential analysis require?

In general, a comparison between randomized groups uses an explicitly defined estimand and statistical method. The estimand describes the treatment contrast of interest, the outcome, the population, and how events such as missing measurements are handled. A model or test then uses the individual observations or sufficient summary information under stated assumptions. The registry record does not report the planned model, covariate adjustment, or detailed analysis strategy for the primary endpoint. It is not possible to infer those choices from the means and standard deviations.

For a continuous outcome, possible general approaches include comparing group means or using a regression model, but the choice depends on the protocol, data structure, distribution, and prespecified analysis plan. This is general statistical context, not a claim about the method used in this study. With only 2 available control observations, assumptions about the distribution and variability are difficult to assess from the summaries. The registry record does not report diagnostic checks, transformations, or robust methods.

How should the planning illustrations be understood?

In general, a sample-size calculation describes how many participants may be needed under stated assumptions to target a chosen precision or power for a specified effect. The planning convention associated with this analysis uses a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect framed as a stated fraction of the observed effect. Such planning illustrations are not observed power, and they are not a record of the trial's original design justification. The registry record does not report its own sample-size justification. No numerical planning estimates are stated in the record details used for this explanation, so no required enrollment for those scenarios can be interpreted.

When planning uses an observed effect from a small study, that effect may be unstable. In general, an unusually large observed contrast can lead to optimistic planning assumptions, while uncertainty around the effect should be considered. The planning illustration is separate from the primary endpoint result and cannot resolve the absence of a formal comparison.

Why can over-dispersion matter?

Over-dispersion is a general concern when observed variability is larger than a statistical model expects. If a model underestimates variability, its uncertainty estimates may be too narrow and inferential results may be misleading. This issue is often relevant to count outcomes, while the primary endpoint is continuous and is posted with standard deviations. The registry record does not report an over-dispersion assessment or a model for the secondary count outcomes. No conclusion about over-dispersion can be drawn from the primary summary statistics.

The registry record identifies the study as randomized, but randomization does not remove uncertainty when few outcome observations are available. Randomization supports a design-based comparison when the analysis and outcome data are adequately specified; it does not guarantee balanced observed groups in a small study. For the available Day 7 data, the difference in group sizes and the small control sample limit what can be learned from the descriptive summaries.

Finally, multiplicity and missing data affect interpretation of any set of trial results. Multiple endpoints or repeated tests can increase the chance of a false-positive result if analyses are selected or interpreted without an appropriate plan. Missing outcomes can also affect comparability, depending on why observations are absent. The registry record does not report multiplicity adjustments, a complete statistical analysis plan, or details about missing-data methods. Those omissions prevent a fuller assessment of inferential validity.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Active Treatment Group: VS-01 on Top of SOC", "Control Group: SOC Alone")
n   <- c(5, 2)
m   <- c(50.852, 39.866)
sp  <- c(15.5459, 6.3557)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Active Treatment Group: VS-01 on Top of SOC  5  50.852  15.546  31.549  70.155
CARM  Control Group: SOC Alone  2  39.866  6.356  -17.238  96.970

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures and reports 9 secondary outcome measures. The secondary outcomes include mortality counts and timing, ACLF resolution, ACLF grade regression, and time to transplant or death. No results for these secondary outcomes are reported in the registry record details. The record does not report a multiplicity strategy, such as a hierarchy, adjustment procedure, or distinction between confirmatory and exploratory testing. Without that information, any collection of endpoint results would need careful interpretation; multiple statistical tests can increase the chance of false-positive findings when considered together.

For the primary endpoint, the analysis population is described as all randomized participants, with only participants who had available data included. The posted summaries use 5 active-group observations and 2 control-group observations. The study enrollment is 15. The registry record does not explain the difference between enrollment and the endpoint analysis counts, identify reasons for unavailable measurements, or state whether missingness was related to group assignment or clinical status.

No imputation method, sensitivity analysis, or missing-data assumption is reported in the registry record. In general, analyzing only observed outcomes can be informative when missingness is unrelated to the outcome after accounting for relevant information, but that condition cannot be evaluated from the posted summaries. If data are missing for reasons associated with outcome values, the observed means may not represent the full randomized groups. The record's analysis-population description therefore needs to be read alongside the limited endpoint denominators.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatic encephalopathy (22.2%), chronic hepatic failure (16.7%), hepatic cirrhosis (16.7%), pneumonia (16.7%), disturbance in attention (16.7%).

The adverse-event figures describe counts of participants affected in each group, not a comparison that establishes causation. In the active group, 7 of 9 participants at risk are reported as affected by serious adverse events; in the control group, 5 of 6 are reported as affected. Other adverse events are reported for 9 of 9 active-group participants and 6 of 6 control-group participants. The death counts are 4 in the active group and 2 in the control group. These figures are descriptive; the registry record does not report a formal comparative safety analysis or establish that an event was caused by VS-01.

The listed serious adverse event terms and percentages are hepatic encephalopathy, 22.2%; chronic hepatic failure, 16.7%; hepatic cirrhosis, 16.7%; pneumonia, 16.7%; disturbance in attention, 16.7%; and gastrointestinal haemorrhage, 16.7%. The registry record details do not clarify the denominator for these term percentages or whether participants could contribute to more than one term. The terms should not be read as mutually exclusive categories or as evidence of a causal relationship. Given the small group sizes and serious underlying condition, the counts alone cannot support a stable comparison of safety between groups.

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

The primary endpoint results establish a limited descriptive fact: among participants with available Day 7 data, the mean CLIF-C ACLF score was 50.85 in the active group and 39.87 in the control group. The score ranges from 0 to 100, and higher scores indicate greater mortality risk. The active-group mean is numerically higher, but the summaries do not establish that assignment to VS-01 caused a difference in score. No formal comparative estimate or uncertainty interval is reported in the registry record.

The small endpoint analysis counts are central to what the results can mean. The active mean is based on 5 participants and the control mean on 2. The study enrolled 15 participants, and only those with available data were included in the primary analysis. The record does not explain why observations were unavailable or how missingness was handled. Therefore, the observed summaries may not represent all randomized participants, and the amount of uncertainty around the group comparison cannot be assessed from a reported inferential result.

The values also do not answer the study's secondary questions about death, time to death, ACLF resolution, grade regression, or time to transplant or death. Although those outcomes are listed in the registry record, their results are not reported in the record details used. Nor do the adverse-event counts establish a treatment-related safety effect. They describe affected participants and deaths in the recorded groups, without a reported causal attribution or comparative analysis.

The terminated status is a fact about the study record, but the reason for termination is not reported in the registry record. It is not possible to attribute the small available endpoint sample to a particular cause or to infer what the investigators would have concluded from a completed analysis. The most defensible interpretation is consequently narrow: the record contains group-level Day 7 summaries for a limited number of observed participants, while the formal treatment comparison and important details about missing outcomes are not reported.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how randomized design and limited outcome availability can coexist. The registry record describes random allocation to VS-01 on top of standard of care or standard of care alone, but the primary endpoint summaries are based on 5 and 2 available observations in the respective groups. Randomization is important for designing a comparison, yet it does not by itself guarantee that the observed endpoint data are complete or sufficiently numerous for a precise estimate.

The distinction between descriptive and inferential evidence is especially important. The means and standard deviations describe the observed scores, but a formal two-arm comparison is not estimable from the posted results. Readers can identify the numerical ordering of the means, while still recognizing that no confidence interval, p-value, or formal treatment estimate is reported. This prevents descriptive values from being mistaken for a settled conclusion.

The record also highlights why analysis populations and missing-data procedures matter. The primary endpoint population is characterized as all randomized participants, but only those with available data contribute to the reported summaries. Without reasons for missingness or sensitivity analyses, it is difficult to know how representative those observations are. The registry lists several secondary outcomes, but their results and the multiplicity approach are not reported in the record details.

Finally, a terminated study with a small available primary-endpoint sample can still contribute transparent descriptive information, but the limits of that information should remain explicit. The statistical value lies in distinguishing what the posted observations directly describe from what would require a fuller analysis: a defined comparison, uncertainty estimates, clear handling of missing data, and results for the registered secondary outcomes.

15. Limitations

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

The main limitation is the number of available observations for the primary endpoint: 5 in the active group and 2 in the control group. The control summary in particular is based on very few participants, so its mean and standard deviation can be sensitive to individual observations. The record does not provide individual participant values, confidence intervals, or a formal comparative estimate. A two-arm comparison is identified as not estimable in the posted continuous endpoint results.

The endpoint analysis includes only participants with available data, even though the population is described as all randomized participants. The reason for the unavailable data, the timing of missingness, and any relationship to group assignment or health status are not reported in the registry record. The record also does not report imputation, sensitivity analysis, or a missing-data assumption. These gaps limit assessment of whether the observed endpoint summaries represent the randomized groups.

The study is open-label, with no masking. The registry record does not describe additional protections against bias in outcome assessment or explain how the score was collected. The record also does not report the randomization method, allocation concealment, protocol-level statistical plan, sample-size justification, interim analyses, or multiplicity strategy. These omissions do not establish that such procedures were absent; they mean they are not reported in the registry record.

The status is terminated, but the reason is not reported. Results for the listed secondary outcomes are not reported in the record details, and the serious adverse event term percentages have no stated denominator or overlap information. Consequently, neither the primary summaries nor the safety counts provide a complete account of comparative efficacy and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy, Safety and Tolerability of VS-01 in Adult Patients With Acute-on-Chronic Liver Failure and Ascites (UNVEIL-IT)® — NCT05900050.
• Registry record last updated 2026-07-23; status last verified 2026-06.
• Results first posted 2026-07-23.
• 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.

19. Record Summary

NCT05900050, UNVEIL-IT, is a Phase 2a randomized, controlled, multicenter, open-label, parallel-group study of VS-01 on top of standard of care versus standard of care alone in adults with acute-on-chronic liver failure. The registry record reports enrollment of 15, a start date of 2023-07-02, a primary completion date of 2025-10-15, and terminated status. The primary endpoint is the CLIF-C ACLF score at Day 7.

The endpoint summaries are a mean of 50.85 with standard deviation 15.55 for 5 active-group participants and a mean of 39.87 with standard deviation 6.356 for 2 control-group participants with available data. A formal two-arm comparison is not estimable from the posted endpoint results. Reasons for unavailable data and the reason for termination are not reported in the registry record. The record lists 9 secondary outcome measures, but their results are not reported in the record details.