Study to Investigate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination for 12 Weeks in Adults With Chronic HCV Infection and Compensated Cirrhosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Investigate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination for 12 Weeks in Adults With Chronic HCV Infection and Compensated Cirrhosis (NCT04112303), a na phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) < Lower Limit of Quantification (LLOQ) 12 Weeks After Discontinuation of Treatment (SVR12).

2. Clinical Question

In practical statistical terms, the study describes an outcome after a treatment course in a defined clinical population. Its single-group structure means the endpoint can describe the observed response proportion in the analysis population, if that result is reported, but it cannot by itself estimate a randomized treatment contrast. Differences between participants who did and did not reach the endpoint would not substitute for a controlled comparison.

The registry lists SVR4, SVR24, and virologic failure among the secondary outcomes. Their names identify additional post-treatment response and failure measures, but numerical results for these outcomes are not reported in the registry record. Interpretation must therefore focus on the trial question and design rather than on an unreported estimate of efficacy.

3. Trial Design

This was a Phase 3, multicenter, open-label, single-group study of SOF/VEL in adults with chronic HCV infection and compensated cirrhosis. The registry lists enrollment of 37 and describes the study as completed. The recorded start date was 2019-10-16, and the primary completion date was 2021-03-26. No randomized allocation or masking is recorded.

All participants were assigned the same study regimen: SOF/VEL 400/100 mg orally once daily for up to 12 weeks. Because there was no concurrent control arm, the trial design supports a descriptive account of outcomes among treated participants but does not provide a randomized comparison with another regimen, placebo, or usual care. The absence of masking also means participants and study personnel knew which treatment was being given. The record does not describe any steps to reduce possible assessment bias.

The primary outcome was assessed at posttreatment Week 12. It was defined as HCV RNA below the LLOQ, with the endpoint description specifying 15 IU/mL. The Full Analysis Set included all enrolled participants who took at least 1 dose of study drug. The record does not report the number analyzed for SVR12, how participants without an assessment were handled, or whether the analysis population differed from enrollment.

The registry identifies five outcome measures and one analysis. It names SVR4, SVR24, and virologic failure as secondary outcomes, in addition to the primary SVR12 measure. However, it does not report the numerical primary result or confidence interval, nor numerical values for the listed secondary outcomes. The study's title and description state that efficacy, safety, and tolerability were objectives; the available numerical safety information is limited to the serious and other adverse-event counts described in the safety discussion.

The record does not report a protocol rationale for the sample size, a planned comparison, or a detailed statistical analysis plan. The single-group design should guide interpretation throughout: the observed outcome, if available, would be a within-study proportion, not a treatment effect estimated against a randomized control group.

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: 41 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set included all enrolled participants who took at least 1 dose of 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: 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 Sustained Virologic Response (SVR) < Lower Limit of Quantification (LLOQ) 12 Weeks After Discontinuation of Treatment (SVR12), measured over Posttreatment Week 12.

The primary endpoint is the percentage of participants with HCV RNA below the lower limit of quantification 12 weeks after discontinuing treatment. The endpoint description defines the threshold as 15 IU/mL and names the measure SVR12. It is a binary outcome at the participant level: each participant either meets the stated virologic criterion at the specified follow-up assessment or does not.

As a general statistical concept, a binary proportion provides a direct description of how often a defined event or status is observed in an analysis population. A confidence interval expresses the statistical uncertainty around an estimated proportion; it indicates a range of values compatible with the data under the method used. Its width depends in part on the amount of information available and on the observed proportion. An interval does not address every source of uncertainty, such as limitations from an uncontrolled design or missing assessments.

SVR12 is used as a post-treatment virologic endpoint because it evaluates whether the specified HCV RNA criterion is met after treatment has stopped, rather than only while a participant is taking study drug. The endpoint definition alone does not establish the result. The numerical SVR12 percentage, its denominator, and its 95% confidence interval are not reported in the registry record, so the endpoint's observed level and precision cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary percentage endpoint and a 95% confidence interval. It does not report the numerical outcome estimate, the confidence interval, or the detailed procedure used to calculate them. The following explanations describe general statistical concepts relevant to this type of endpoint; they do not fill in missing trial results or establish which analysis method the study used.

What does a binary percentage represent?

A binary endpoint classifies each participant according to whether a stated condition is met. For SVR12, the condition is HCV RNA below the LLOQ 12 weeks after treatment discontinuation. The percentage is an estimate of the fraction of participants in the analysis population who meet that criterion. To interpret it fully, a reader needs both the number meeting the endpoint and the number included in the denominator, as well as the rule for handling missing measurements. Those numerical details are not reported in the registry record.

A percentage is a descriptive summary, not a causal comparison. In a single-group study, it characterizes the outcome in the treated study population under the study's conditions. It does not estimate the difference between outcomes under SOF/VEL and outcomes under a comparator condition. The absence of a randomized control group is especially important when interpreting efficacy claims, because other differences and changes over time cannot be separated from the treatment experience by a between-group contrast.

What does a confidence interval add?

In general, a confidence interval communicates uncertainty in an estimate arising from sampling variation under a specified statistical model. A narrower interval indicates greater statistical precision than a wider interval, all else being comparable. It is not a guarantee that the true value lies within the particular reported interval, and it does not account automatically for selection bias, measurement problems, missing data, or the lack of a control group. The registry specifies a 95% confidence interval for the primary endpoint, but the interval itself is not reported in the registry record. Consequently, its width and the precision of the estimate cannot be assessed.

For a percentage, interval methods can differ, particularly when the number of observations is limited or the estimated proportion lies near a boundary. The registry record does not state which interval method was used. It would therefore be inappropriate to reconstruct an interval or imply that a particular method was prespecified.

Why does the analysis population matter?

The Full Analysis Set is defined as all enrolled participants who took at least 1 dose of study drug. That definition identifies who is intended to contribute to the primary analysis, but the record does not report the number with an evaluable SVR12 assessment or the analysis denominator. It also does not say whether participants who stopped treatment early, missed follow-up, or had other deviations were included in the endpoint calculation. The definition should not be mistaken for proof that every person in the set had a measured outcome.

In general, an analysis population is part of the estimand: it helps define the question that an estimate answers. Different participant sets can yield different proportions if their members or outcome availability differ. Transparent reporting of the population, denominator, and missing-data rules is therefore needed to understand exactly what a reported percentage represents. These details, beyond the Full Analysis Set definition, are not reported in the registry record.

What can a single-group design estimate?

A one-group proportion can describe what was observed in the study cohort. A randomized comparison, by contrast, estimates the difference between outcomes in groups assigned to different conditions, subject to its design and analysis assumptions. Because this study is recorded as single-group with allocation listed as not applicable, the primary outcome cannot be interpreted as a randomized treatment effect. Comparing the observed proportion with an external benchmark would require a justified benchmark and assumptions about comparability; neither is specified in the registry record.

The study was open-label, with masking listed as none. As a general matter, awareness of treatment can influence behavior, follow-up, co-interventions, or assessment processes. A virologic laboratory measure may be less subjective than a judgment-based outcome, but the record does not describe laboratory procedures or blinding of assessors. It is not possible to determine from the registry record whether any such safeguards were used.

How should the planning assumptions be read?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are assumptions for an illustrative sample-size calculation, not evidence that the trial itself used a two-arm design. The actual study is single-group. The record also states that time-to-event illustrations use a total event count, while other illustrations use participants per arm. No planning values are reported, and an illustrative sample-size result would not be an observed outcome or observed power.

In general, over-dispersion arises when observed variability exceeds what a model assumes. For a binary percentage, an analysis that assumes independent observations may be too precise if outcomes are correlated within clusters or if the data otherwise vary more than the model allows. The registry record does not describe a clustered design or report an over-dispersion adjustment, so this is a general consideration rather than a feature that can be attributed to this study.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("SOF/VEL")
n      <- c(37)
events <- c(37)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  SOF/VEL  37  37  100.0  90.5  100.0  90.6  100.0  90.7  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies five outcome measures and one analysis. The primary outcome is SVR12; the named secondary outcomes include SVR4, SVR24, and virologic failure. The record does not provide numerical results for these outcomes, and it does not report a multiplicity adjustment or a hierarchy for interpreting them.

As a general statistical concept, testing or interpreting multiple outcomes can increase the chance of finding at least one apparently notable result by chance. Prespecified outcome priorities and statistical adjustments can help control how that risk is interpreted. The outcome count and names alone do not establish how many formal hypotheses were tested, which were considered confirmatory, or whether any adjustment was used. Those details are not reported in the registry record.

The primary analysis population is defined as all enrolled participants who took at least 1 dose. However, the record does not report the primary endpoint denominator, the number with an observed posttreatment Week 12 measurement, or how missing data were handled. It also does not describe whether sensitivity analyses assessed alternative missing-data assumptions. This matters because a percentage depends on both the outcome classification and the treatment of participants whose status is unavailable.

The record does not report whether there were interim analyses, nor does it provide a detailed statistical analysis plan. Those aspects should not be inferred from the trial's Phase 3 designation or from the endpoint definitions. As a result, the available information does not support an assessment of how multiplicity, missing observations, or analysis choices may have influenced the primary estimate.

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: patella fracture (2.7%).

The registry lists one SOF/VEL group, with 37 participants at risk for serious adverse events and 1 affected. For other adverse events, it lists 37 at risk and 5 affected. It also reports 1 death. A serious adverse-event term listed among the top terms is patella fracture, reported as 2.7%.

These are descriptive figures for the study group, not a comparison of adverse-event rates between treatments. The record does not explain the relationship between the reported death and adverse-event counts, provide event timing or narratives, or state whether events were judged related to study treatment. The listed term and percentage should not be used to infer details that are not reported in the registry record.

In general, adverse-event counts depend on how events are defined, collected, and attributed, and they do not by themselves establish causation. The at-risk counts identify the group considered for the event summaries, but the registry does not provide exposure-adjusted rates or a detailed safety analysis. These figures describe what the record reports; they do not establish a comparative safety profile.

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

The study record answers a specific design question: it describes a Phase 3, open-label, single-group assessment of SOF/VEL in adults with chronic HCV infection and compensated cirrhosis. The primary endpoint was defined as HCV RNA below the LLOQ 12 weeks after treatment discontinuation, with the threshold stated as 15 IU/mL. The treatment regimen and Full Analysis Set definition are also recorded.

However, the numerical SVR12 result and its 95% confidence interval are not reported in the registry record. This means the central efficacy estimate cannot be described or judged for precision from the record. The endpoint definition is not itself a result. It does not indicate how many participants met the criterion, what proportion did so, or how uncertain an estimate would be.

Even if a numerical one-group result were available, it would describe outcomes among participants in this study rather than a randomized difference between SOF/VEL and a comparator. Without a control group, the design does not establish what would have happened to comparable participants under another condition. The study's open-label status and the unreported details of follow-up and missing-data handling also matter when considering how outcomes were collected and analyzed.

The posted safety counts provide limited descriptive information: the record reports serious and other adverse events in the SOF/VEL group, along with a death count and a serious-event term. These counts do not establish that treatment caused or did not cause an event, and they cannot show how safety compares with another treatment.

The most defensible reading is therefore bounded. The record documents the population, regimen, endpoint definition, design, and selected adverse-event figures. It does not report the numerical primary result, its precision, or enough comparative information to support a controlled treatment-effect conclusion. The named secondary outcomes likewise do not have numerical results reported in the registry record.

14. Why This Trial Matters Statistically

Statistically, this trial is useful for illustrating the distinction between a clearly defined endpoint and a reported estimate. SVR12 is specified with a follow-up time and laboratory threshold, and the intended Full Analysis Set is defined. Those features help a reader understand what the primary outcome was meant to measure. Yet without the percentage, confidence interval, denominator, and missing-data approach, the endpoint cannot be quantitatively interpreted.

The single-group design also makes the estimand important. A response proportion in a treated cohort is not the same quantity as a difference between treatment groups. Recognizing that distinction prevents a descriptive outcome from being treated as a comparative effect. The registry's design fields make clear that no randomized comparator is recorded, even though the study is Phase 3.

The record also illustrates why safety counts need context. Counts of affected participants can summarize reported events, but they do not communicate comparative risk, causation, timing, or exposure-adjusted frequency on their own. Such interpretation requires more detail than the registry lists.

Finally, the record identifies multiple outcomes and a planning illustration, but does not report a detailed analysis plan, multiplicity strategy, or missing-data procedures. These omissions limit reproducibility and assessment of statistical uncertainty. The appropriate statistical conclusion is not that an unreported effect is large, small, precise, or imprecise; it is that the record defines important analysis questions while leaving their numerical answers unreported.

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 most consequential limitation for interpreting efficacy is that the registry record does not report the numerical SVR12 percentage or its 95% confidence interval. It also does not report the endpoint denominator or the number with an evaluable posttreatment Week 12 measurement. As a result, the primary outcome's observed level and precision cannot be assessed.

The single-group design provides no randomized control comparison. This limits causal interpretation because outcomes under another treatment or no study treatment are not observed in a concurrent group. The open-label design is another feature to consider; the record does not describe masking of laboratory or outcome assessments.

The Full Analysis Set is defined, but additional analysis details are not reported in the registry record. These include how missing SVR12 measurements were handled, whether participants who discontinued treatment remained in the analysis, and whether sensitivity analyses were conducted. Such information is important for understanding the denominator and robustness of a binary endpoint estimate.

The registry names secondary outcomes but does not report their numerical results. It also does not report a multiplicity strategy, detailed statistical analysis plan, or whether interim analyses occurred. The record does not provide the sample-size rationale for the trial itself. Its planning assumptions describe an illustration rather than the design of the single-group study, and no planning values are reported in the registry entries.

Safety information is limited to selected counts and a serious-event term. Timing, event descriptions, treatment attribution, and comparative safety information are not reported in the registry record. These limits mean the listed figures should be understood as a narrow descriptive account, not a full safety evaluation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Investigate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination for 12 Weeks in Adults With Chronic HCV Infection and Compensated Cirrhosis — NCT04112303.
• Registry record last updated 2022-04-20; status last verified 2022-03.
• Results first posted 2022-04-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT04112303 is a completed Phase 3, multicenter, open-label, single-group study sponsored by Gilead Sciences. It enrolled 37 adults with chronic HCV infection and compensated cirrhosis. Participants received SOF/VEL 400/100 mg orally once daily for up to 12 weeks. The recorded study start was 2019-10-16, and primary completion was 2021-03-26.

The primary outcome was SVR12, defined as HCV RNA below the LLOQ 12 weeks after treatment discontinuation; the endpoint description gives the LLOQ as 15 IU/mL. The Full Analysis Set included enrolled participants who took at least 1 dose. The numerical primary result, confidence interval, endpoint denominator, and missing-data method are not reported in the registry record.

The registry lists SVR4, SVR24, and virologic failure as secondary outcomes. It reports serious and other adverse-event counts for the SOF/VEL group and 1 death. With no concurrent comparator and no numerical primary outcome result reported, the record supports description of the study design and reported safety counts, but not a quantitative or randomized estimate of treatment effect.