Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Participants With Chronic HCV: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Participants With Chronic HCV (NCT02671500), a na phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

In a single-group study, the observed endpoint can describe outcomes among participants who received the study treatment, but it cannot by itself establish how those outcomes compare with what would have occurred under a different treatment or no treatment. The registry lists secondary outcomes involving SVR at other follow-up times, on-treatment HCV RNA, change from baseline, and overall virologic failure. Those additional outcomes do not change the primary question: the stated primary endpoint is a proportion meeting the registry's SVR12 definition.

3. Trial Design

This was a phase 3, multicenter, open-label, single-group study of SOF/VEL fixed-dose combination for 12 weeks in participants with chronic HCV infection. The registry lists 375 participants enrolled and records the study as completed. It identifies Gilead Sciences as the sponsor. The study's stated objectives were to evaluate efficacy, safety, and tolerability.

The design has no randomized allocation and no masking. All participants were assigned to the single listed treatment group; the registry does not describe a concurrent control group. The record therefore supports a description of outcomes in the treated study population, rather than a randomized treatment-effect comparison. In particular, differences between this group's outcomes and outcomes from another population or study would not be protected by randomization and could reflect differences in participants, care, follow-up, or other conditions.

Open-label means masking was absent. Knowledge of treatment assignment can matter differently for different outcomes: a laboratory-defined viral response is less dependent on subjective judgment than an outcome based on participant or investigator assessment, while reporting and recording of some safety events may be influenced by awareness. The registry does not provide further detail about outcome adjudication or procedures used to limit assessment bias.

The primary endpoint was the percentage of participants with SVR12, assessed at posttreatment week 12. The Full Analysis Set included participants who enrolled and received at least one dose. The registry lists SVR4, SVR24, on-treatment HCV RNA measures, change from baseline in HCV RNA, and overall virologic failure among the secondary outcomes. The primary endpoint's numerical result and confidence interval are not reported in the registry record. Details such as the intended sample-size justification, recruitment targets by subgroup, interim analyses, and detailed statistical analysis plan are also not reported in the registry record.

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: 437 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 participants who were enrolled into the study and received 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 participants who were enrolled into the study and received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12), measured over Posttreatment Week 12.

The primary endpoint is the percentage of participants with sustained virologic response 12 weeks after discontinuing treatment, abbreviated SVR12. The registry defines a response as HCV RNA below the lower limit of quantitation (LLOQ), specified as 15 IU/mL, at 12 weeks after stopping study treatment. It is a binary outcome at the participant level: each participant either meets the stated response definition at that follow-up assessment or does not.

A percentage expresses how common the defined outcome was in the analysis population. It is useful for describing the frequency of a clinically interpretable endpoint, but it does not, by itself, quantify a causal treatment effect. That distinction is especially important in a single-group study, where there is no randomized comparator to establish what would have happened to the same kind of participants under another condition.

SVR12 is used as a follow-up measure because it assesses whether the viral response is present after treatment has stopped, rather than only while participants are receiving therapy. The registry also lists SVR at 4 and 24 weeks after treatment discontinuation as secondary outcomes. Those follow-up measures address different assessment times and should not be treated as interchangeable with the primary endpoint.

The registry record does not report the numerical SVR12 percentage or its 95% confidence interval. It therefore permits a clear description of what the endpoint was intended to measure, but not a numerical account of how many participants met it or how precisely the percentage was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a percentage, with a 95% confidence interval, in the Full Analysis Set. It does not provide the numerical estimate, interval limits, or enough analysis detail to reconstruct the sponsor's calculation. The concepts below explain how this type of endpoint is generally interpreted; they should not be read as a description of unreported procedures used in this study.

What does a percentage endpoint represent?

For a binary endpoint, each participant is classified according to whether the prespecified event or condition is present. The estimated percentage describes the proportion meeting that definition in the analysis population. In this study, the qualifying condition was HCV RNA below the LLOQ of 15 IU/mL at posttreatment week 12. The registry calls that outcome SVR12.

The estimate depends on both the outcome classification and the denominator. A percentage may be calculated among participants with observed endpoint data, or under a specified rule for participants whose endpoint status is missing. Those approaches answer different operational questions. The registry defines the Full Analysis Set as enrolled participants who received at least one dose, but does not report the number with an observed SVR12 assessment or how missing endpoint results were handled. The exact denominator used for the posted percentage is therefore not available in the registry record.

How should a confidence interval be read?

In general, a confidence interval represents uncertainty in an estimate under the assumptions of the method used. Its width reflects statistical precision: a narrower interval indicates less sampling uncertainty than a wider interval, all else being equal. It does not account automatically for every possible source of bias, such as missing follow-up, measurement problems, or limitations of a single-group design. The record specifies a 95% confidence interval for the primary endpoint, but does not report its numerical limits. Precision cannot be judged without those limits.

A confidence interval is not a comparison. For a single-group percentage, it describes uncertainty about that group's endpoint estimate. It does not provide the difference between SOF/VEL and a control group, because no control group is listed. It also cannot remove confounding or other systematic differences that would matter in a nonrandomized comparison.

Why does the study design matter to the analysis?

Randomization creates treatment groups that can be compared while reducing systematic differences in expectation. This study is recorded as single-group, with allocation listed as not applicable and masking absent. Consequently, its primary endpoint is a within-group description rather than a randomized contrast. The open-label design also means treatment assignment was not masked; the registry does not report additional details about blinded outcome assessment.

Even when an endpoint is objectively defined, the design still determines what can be inferred. A laboratory threshold provides a clear rule for classifying SVR12, but a clear rule does not create a comparator. The study can describe the proportion meeting the rule among its analyzed participants; it cannot identify, from this design alone, the difference attributable to treatment relative to an alternative.

What can be said about sample-size planning?

The intended sample-size justification and its assumptions are not reported in the registry record. A planning illustration based on an observed effect is not the same as the original design calculation, and it is not observed power. In general, planning calculations depend on assumptions about the effect to detect, the significance level, allocation, and statistical method. A result from such a calculation describes a hypothetical design under those assumptions, not evidence that the study had a particular probability of detecting an effect after the data were observed.

Because no randomized arms are listed, two-arm planning assumptions would not describe the actual design recorded for this trial. The registry does not report a protocol-based sample-size rationale or interim-analysis plan. No inference about those design decisions should be made from the enrollment count alone.

What do secondary outcomes add?

The registry lists SVR4 and SVR24, HCV RNA below the LLOQ on treatment, change from baseline in HCV RNA, and overall virologic failure as secondary outcomes. In general, multiple outcomes can provide complementary descriptions, but they also raise questions about which results were prespecified as primary, how comparisons were prioritized, and whether adjustments were planned when many hypotheses are tested. The registry does not report a multiplicity-adjustment strategy. Numerical secondary-outcome findings are not reported in the registry record, so their values and uncertainty cannot be interpreted.

The statistical interpretation should therefore remain bounded by the recorded information: an explicitly defined binary primary endpoint, a named analysis population, a 95% confidence-interval measure, and a single-group open-label design. The numerical endpoint result, interval limits, missing-data procedures, and detailed analysis methods are not reported in the registry record.

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 (Overall)", "SOF/VEL (China - Region 1)", "SOF/VEL (Southeast Asia - Region 2)")
n      <- c(375, 264, 111)
events <- c(362, 254, 108)
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 (Overall)  375  362  96.5  94.1  98.1  94.2  98.0  94.2  97.9
ARM  SOF/VEL (China - Region 1)  264  254  96.2  93.1  98.2  93.2  97.9  93.2  97.9
ARM  SOF/VEL (Southeast Asia - Region 2)  111  108  97.3  92.3  99.4  92.4  99.1  92.4  99.0

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome and lists several secondary outcomes. A primary endpoint gives a central outcome for interpreting a study, while additional outcomes can address other times or aspects of response. When multiple outcomes are assessed, the chance of finding at least one apparently notable result can increase if each is tested separately. Statistical plans may address this through a testing hierarchy, multiplicity adjustment, or another prespecified approach. The registry record does not report whether any such approach was planned or used.

The primary endpoint's numerical estimate and 95% confidence interval are not reported in the registry record. The record also does not report numerical results for the listed secondary outcomes. Therefore, the outcome hierarchy cannot be evaluated from reported estimates, and no claim about statistical significance or consistency across outcomes is possible.

The Full Analysis Set is defined as participants who enrolled and received at least one dose of study drug. The registry does not report how many members of that set had an SVR12 assessment, the amount or pattern of missing endpoint data, or the rules used to classify participants with missing results. It also does not report whether sensitivity analyses examined alternative missing-data assumptions.

Missing-data handling matters because a percentage can depend on whether participants without an observed endpoint are excluded, counted as not meeting the criterion, or handled under another rule. These are general possibilities, not descriptions of what this study did. Without the analysis details and endpoint status counts, the effect of missing data on the reported estimate cannot be assessed.

The record defines the primary analysis population but does not report additional analysis populations or the statistical plan for handling protocol deviations. Those details, along with multiplicity procedures, missing-data methods, and interim-analysis information, are not reported in the registry record.

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: diabetic foot infection (0.3%), pneumonia (0.3%), ligament rupture (0.3%).

For the listed SOF/VEL group, the registry reports 375 participants at risk for serious adverse events and 3 affected. It reports 375 at risk for other adverse events and 36 affected. These are descriptive counts for the study group; they do not provide a comparison with another treatment or control group. The record also reports zero deaths in the group.

The listed serious adverse-event terms are diabetic foot infection, pneumonia, and ligament rupture, each reported as 0.3%. These term-specific percentages should be read as the registry's reported values, not as evidence that the events were caused by the study treatment. A serious adverse event is a safety classification; the registry information presented does not establish causal attribution for each event.

Counts and percentages do not describe every aspect of safety. They do not, by themselves, convey event timing, duration, recurrence, severity beyond the serious classification, or the participants' clinical circumstances. The registry record does not report additional detail on those matters in the information available for this analysis. Because the study had no comparator group, the figures describe what was recorded among participants in the treated group, not a relative risk or treatment-attributable excess.

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

The record establishes that a phase 3, multicenter, open-label, single-group study evaluated SOF/VEL fixed-dose combination for 12 weeks in participants with chronic HCV. It specifies a primary endpoint based on HCV RNA at posttreatment week 12 and defines the Full Analysis Set. It also records selected adverse-event counts and identifies three serious adverse-event terms, each reported as 0.3%.

The record does not report the numerical SVR12 percentage or its 95% confidence interval. As a result, the primary efficacy estimate and its precision cannot be described. The listed secondary outcomes also lack numerical findings in the registry record. There is therefore no basis in this record for stating how frequently participants met the primary endpoint or how secondary virologic outcomes varied over time.

Even if the primary percentage were available, a single-group study would describe the outcome in the treated group rather than provide a randomized comparison with another option. Without a comparator, the observed result cannot by itself distinguish treatment effects from participant characteristics, other care, natural disease course, or other influences. The open-label design and unreported details about outcome assessment add further limits to what can be inferred.

The safety figures show counts and selected event terms recorded for the study group. They do not establish causation, comparative safety, or the likelihood of an event under another treatment. Zero deaths are recorded, but that fact alone does not characterize the full safety profile.

Accordingly, the registry record supports a description of the design, endpoint definition, analysis population, and selected safety data. It does not support a numerical conclusion about SVR12 or a causal conclusion about efficacy or safety. Missing endpoint results, confidence-interval limits, missing-data procedures, and further analysis details are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a suitable design answer different statistical questions. The SVR12 definition is operationally specific: HCV RNA had to be below the LLOQ of 15 IU/mL at posttreatment week 12. That rule clarifies what counts as a response. But precision about the endpoint does not supply the numerical result, and it does not provide a comparison group.

The study's single-group structure also shows the distinction between describing an outcome and estimating a comparative treatment effect. A response percentage can summarize the treated participants' observed outcomes. A randomized comparison is needed to support a direct contrast protected by random allocation. The registry lists no comparator, so interpretation must remain descriptive even if an estimate is available elsewhere.

Another statistical issue is the connection between the analysis population and missing outcomes. The Full Analysis Set includes participants who enrolled and received at least one dose, but the registry does not report how many had an observed SVR12 assessment or how missing values were treated. A population definition alone is not enough to understand the denominator and assumptions behind a percentage.

Finally, a confidence interval is important because an estimate has uncertainty, but the registry reports only that a 95% confidence interval was the dispersion measure, not its limits. Without the estimate and interval, neither the frequency of SVR12 nor its precision can be judged. The record thus offers a useful example of how a complete endpoint definition can coexist with unavailable numerical outcome reporting.

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 direct limitation for interpreting efficacy is that the numerical primary outcome and its 95% confidence interval are not reported in the registry record. Without them, the main endpoint's observed frequency and precision cannot be described. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study is single-group and has no randomized comparator. This limits causal interpretation: outcomes in the treated group cannot be directly contrasted with outcomes under another treatment or control condition. The open-label design means masking was absent. The registry does not report whether outcome assessors were otherwise blinded or whether additional procedures were used to reduce assessment bias.

The Full Analysis Set definition is available, but the number of participants with observed SVR12 data, the handling of missing endpoint status, and sensitivity analyses are not reported in the registry record. Those omissions prevent assessment of whether incomplete follow-up could affect the endpoint percentage. Further details about protocol deviations and analysis populations are also not reported.

The registry does not report the sample-size justification, detailed statistical analysis plan, multiplicity strategy, or interim analyses. These omissions mean that planned assumptions and decision rules cannot be evaluated. The enrollment count alone does not establish the intended precision or power of the study.

Safety reporting is limited to the listed counts, deaths, and selected serious adverse-event terms. The record does not provide comparative safety data or enough detail to determine causation, timing, or the broader context of the events. These limitations are specific to the information recorded and do not establish that unreported analyses were or were not conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks in Participants With Chronic HCV — NCT02671500.
• Registry record last updated 2019-01-08; status last verified 2018-12.
• Results first posted 2019-01-08.
• 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

NCT02671500 is a completed phase 3, multicenter, open-label, single-group study of SOF/VEL fixed-dose combination for 12 weeks in participants with chronic HCV. The registry lists enrollment of 375 and identifies Gilead Sciences as sponsor.

The primary endpoint was the percentage with SVR12, defined as HCV RNA below the LLOQ of 15 IU/mL at posttreatment week 12. The Full Analysis Set included enrolled participants who received at least one dose. The numerical SVR12 result and its 95% confidence interval are not reported in the registry record.

The record reports 3 participants affected by serious adverse events and 36 affected by other adverse events among 375 at risk in each category, with zero deaths. Diabetic foot infection, pneumonia, and ligament rupture are each listed at 0.3%. The design has no comparator, and the registry does not report detailed missing-data methods, multiplicity procedures, or the statistical analysis plan.