Safety and Efficacy of Voxilaprevir Plus Sofosbuvir/Velpatasvir Fixed Dose Combination in Adults With Chronic Non-Genotype 1 HCV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Voxilaprevir Plus Sofosbuvir/Velpatasvir Fixed Dose Combination in Adults With Chronic Non-Genotype 1 HCV Infection (NCT02378961), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12).

2. Clinical Question

The study’s stated objectives were to evaluate safety, tolerability, and efficacy of the drug combination in adults with chronic non-genotype 1 HCV infection. Its endpoint framework focuses on whether HCV RNA remains below the assay’s quantitation limit after treatment has ended, rather than only whether RNA falls during treatment. The registry also lists SVR4 and SVR24, on-treatment HCV RNA below the lower limit of quantitation, change in HCV RNA from baseline, and virologic failure as secondary outcomes.

Because treatment assignment was non-randomized and sequential, differences between regimen groups should not be read as if participants had been randomly assigned to otherwise comparable options. Treatment history, cirrhosis status, treatment duration, and the sequence in which groups were studied can all be relevant to interpretation. The registry record does not report a randomized comparison or establish that the groups were designed to estimate causal differences between regimens. The primary question is therefore descriptive: the registry specifies an outcome and population, but a numerical SVR12 estimate is not reported in the available record.

3. Trial Design

NCT02378961 is listed as a phase 2, global, multicenter, open-label study. It was non-randomized, used no masking, and followed a sequential model. The registry records enrollment of 128 and describes the study as completed. It lists chronic hepatitis C virus infection as the condition and Gilead Sciences as the sponsor. The study started on 2015-02-16, with primary completion on 2015-09-21.

The intervention was VOX plus SOF/VEL, with regimen descriptions spanning 6, 8, and 12 weeks. The descriptions distinguish treatment-naive from treatment-experienced participants and cirrhotic from non-cirrhotic participants. Those differences define clinically relevant subgroups, but they also mean that group outcomes need not be directly comparable. In particular, the sequential, non-randomized design does not ensure that participants assigned to different regimens had the same baseline characteristics or were enrolled under the same conditions.

Open-label means that the study was not masked, according to the registry. The record does not report further details on masking procedures because none are listed. The registry’s group descriptions and adverse-event entries do not constitute a randomized control comparison. No protocol for assigning participants among the sequential regimens is reported in the registry record.

The primary outcome was the percentage of participants with SVR12 after discontinuing therapy, assessed at Posttreatment Week 12. The primary endpoint description defines response using HCV RNA below the lower limit of quantitation. The designated population is the Full Analysis Set, defined as participants who received at least 1 dose of study drug. The registry also names outcomes at SVR4 and SVR24, on-treatment RNA response, change from baseline, and virologic failure. Numerical primary efficacy results and analysis details for those outcomes are not reported in the registry record.

Enrollment is a study-level registry figure, not a substitute for the analyzed denominator of any specific outcome. The record does not report endpoint-specific participant counts or explain whether all enrolled participants contributed to each listed outcome. Accordingly, the study’s design can be characterized, but the available registry entries do not support reconstructing a complete efficacy analysis.

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: 171 participants were screened. Enrollment was sequential, with the longer treatment duration groups enrolled, treated, and evaluated for Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) prior to enrollment of the shorter treatment duration groups, which were not enrolled, at the discretion of the Sponsor.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): participants who 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: participants who 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 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 discontinuation of therapy, assessed at Posttreatment Week 12. The registry defines SVR12 as HCV RNA below the lower limit of quantitation 12 weeks after the last dose of study treatment. The stated analysis population is the Full Analysis Set, meaning participants who received at least 1 dose of study drug.

As a general statistical concept, a binary endpoint classifies each participant as either meeting or not meeting a defined response criterion. Reporting a percentage describes the frequency of participants meeting that criterion within the analysis population. The confidence interval communicates uncertainty around the estimated percentage; it is not a range containing a known fixed value with certainty. Its width depends in part on the amount of information available and the observed pattern of responses.

SVR12 is used as a post-treatment measure because it assesses virologic status after therapy has stopped, rather than measuring only an on-treatment change. It also gives the endpoint a consistent definition tied to a specific follow-up time and laboratory threshold. The registry lists SVR4 and SVR24 as secondary outcomes, but the primary endpoint is SVR12. A numerical SVR12 estimate, confidence interval, and endpoint-specific denominator are not reported in the registry record, so the magnitude and precision of the primary result cannot be described from that record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

The primary outcome is a binary response summarized as a percentage: participants either met the SVR12 definition or did not. The registry defines meeting the endpoint as HCV RNA below the lower limit of quantitation 12 weeks after the last dose of study treatment. A percentage is a compact description of the observed response frequency in the analysis population. It does not, on its own, describe how responses are distributed across treatment-history or cirrhosis subgroups.

General explanation: an estimate from a clinical study is subject to sampling uncertainty. A confidence interval is a range calculated by a statistical procedure to express that uncertainty. It should be interpreted as an indication of precision, not as a guarantee that the true value lies inside the particular interval. The registry specifies a 95% confidence interval as the dispersion measure for the primary outcome, but does not report the numerical estimate or interval.

Why does the analysis population matter?

The record names the Full Analysis Set as the primary endpoint population and defines it as participants who received at least 1 dose of study drug. The outcome denominator should correspond to the participants whose endpoint status was included in the analysis, not automatically to the study’s overall enrollment. The record does not give the endpoint-specific denominator or describe how participants without a recorded SVR12 status were handled. That prevents readers from checking the reported percentage against its analysis population, even if the percentage had been listed.

General explanation: different analysis populations can answer different questions. A population based on treatment receipt excludes people who never started study drug, while other definitions may include or exclude participants according to protocol adherence or availability of follow-up. Those choices can affect interpretation. Only the Full Analysis Set definition stated in the registry is available for the primary outcome; additional analysis-population definitions and their use are not reported in the registry record.

What does the design permit readers to compare?

The study was non-randomized, open-label, and sequential. Random assignment is one method for balancing both measured and unmeasured participant characteristics across treatment groups. Without it, group membership may be related to characteristics that also relate to outcomes. Sequential enrollment can also mean that groups were studied in different periods or circumstances, but the specific sequence and its operational details are not reported in the registry record.

General explanation: an unadjusted difference between groups is descriptive unless the design and analysis support a causal interpretation. Adjustment for measured characteristics may address some observed imbalance, but cannot necessarily account for unmeasured differences. No comparative analysis or adjustment method is reported in the registry record. The arm descriptions vary by treatment duration, treatment history, and cirrhosis status, so direct interpretation of between-group contrasts would be especially cautious.

How should the confidence interval be read?

The registry identifies a 95% confidence interval for the primary outcome. General explanation: an interval combines an estimate with information about uncertainty under a statistical procedure. If the estimate is close to a boundary, methods for calculating an interval may matter because a percentage is bounded. The registry record does not state the interval method, so it is not possible to assess which calculation was used. Nor is there a numerical interval in the record to evaluate its width.

Precision and design validity are different issues. A narrow interval can still describe a biased or poorly comparable estimate if the design does not support the intended interpretation. Conversely, a broad interval indicates uncertainty even when the design is appropriate. Because the registry does not report the primary estimate or interval, neither precision nor the range of plausible response values can be assessed from this record.

Why can over-dispersion matter?

General explanation: over-dispersion occurs when observed variability exceeds what a statistical model assumes. In count outcomes or clustered data, ignoring excess variability can make uncertainty appear smaller than it is. This is not a conclusion about this study: the registry record does not report a model for the binary primary endpoint, evidence of over-dispersion, or a method for addressing it. The concept is relevant when reviewing a statistical analysis, but it cannot be attributed to this trial without further information.

What does the safety count describe?

The serious adverse event figures are counts within the listed group sizes. They describe the serious-event entries recorded for those groups, not a randomized comparison of safety. General explanation: event counts can be informative descriptively, while formal comparisons require attention to the time each participant was observed, the definition of an event, and the analysis approach. The registry record does not provide those details for these entries. It also does not report death counts; the death fields are not populated.

The record names gastroenteritis at 3.4% among the top serious terms. It does not report the denominator or additional context for that percentage in the listed details, so its precision and relation to the group-specific counts cannot be evaluated from this record. Serious events and other adverse events are distinct categories; the other-event counts should not be substituted for serious-event counts.

What is not available about the analysis?

The record lists no statistical analyses. It does not report hypothesis tests, estimates for the primary endpoint, an analysis model, multiplicity handling, missing-data procedures, interim analyses, or sample-size justification. These omissions mean readers cannot reconstruct the planned or performed efficacy analysis. General methods can explain what such procedures would address, but they cannot fill in the trial’s undocumented choices. The registry record is therefore informative about the endpoint definition and broad design, but not a complete statistical report of the primary efficacy analysis.

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("VOX+SOF/VEL 6 Weeks, Treatment Naive, Non Cirrhoti", "VOX+SOF/VEL 8 Weeks, Treatment Naive, Cirrhotic", "VOX+SOF/VEL 12 Weeks, Treatment Experienced, Non C", "VOX+SOF/VEL 12 Weeks, Treatment Experienced, Cirrh")
n      <- c(33, 30, 36, 29)
events <- c(29, 28, 36, 28)
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  VOX+SOF/VEL 6 Weeks, Treatment Naive, Non Cirrhoti  33  29  87.9  71.8  96.6  72.7  95.2  72.5  95.0
ARM  VOX+SOF/VEL 8 Weeks, Treatment Naive, Cirrhotic  30  28  93.3  77.9  99.2  78.7  98.2  78.6  98.0
ARM  VOX+SOF/VEL 12 Weeks, Treatment Experienced, Non C  36  36  100.0  90.3  100.0  90.4  100.0  90.5  99.9
ARM  VOX+SOF/VEL 12 Weeks, Treatment Experienced, Cirrh  29  28  96.6  82.2  99.9  82.8  99.4  82.8  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary SVR12 outcome and several secondary outcomes: SVR4 and SVR24, on-treatment HCV RNA below the lower limit of quantitation, change in HCV RNA from baseline, and virologic failure. It does not report how statistical testing across these outcomes was handled. In particular, multiplicity adjustment, a hierarchy of tests, or a distinction between confirmatory and exploratory analyses is not reported in the registry record.

General explanation: when several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed separately. A prespecified testing strategy can help control that issue and clarify which findings are confirmatory. The registry record does not describe such a strategy, so the strength of any hypothetical secondary finding cannot be evaluated within a stated multiplicity framework. Numerical secondary results are also not reported in the record.

The primary population is defined as participants who received at least 1 dose of study drug. The record does not state how missing SVR12 measurements, withdrawals, or participants without follow-up were classified or handled. Missing-data assumptions and sensitivity analyses are not reported in the registry record. This matters because a percentage endpoint depends on how participants without an observed outcome are treated and on which participants form its denominator.

The record lists no statistical analyses. It does not report the primary endpoint denominator, a missing-data method, or an analysis plan. Accordingly, the registry supports description of the stated population and endpoint definition, but not independent assessment of how incomplete outcome data or multiple outcomes may have affected the analysis.

12. Safety Results

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

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: gastroenteritis (3.4%).

The registry reports serious adverse event counts for four groups: 0 among 33 participants in the 6-week treatment-naive, non-cirrhotic group; 0 among 30 in the 8-week treatment-naive, cirrhotic group; 0 among 36 in the 12-week treatment-experienced, non-cirrhotic group; and 1 among 29 in the 12-week treatment-experienced, cirrhotic group. The record lists gastroenteritis at 3.4% among the top serious terms. Death counts are not reported in the registry record.

These figures are descriptive. They indicate the serious-event entries recorded within the listed groups, but do not establish a relative safety difference between regimens. The study was non-randomized and sequential, and the groups are not like-for-like controls. Their treatment history, cirrhosis status, and treatment duration differ. The registry record does not report event observation time, a comparative safety analysis, or further context for the gastroenteritis percentage.

General explanation: serious adverse events are not interchangeable with all adverse events. The record separately lists other adverse-event counts, but those counts should not be interpreted as serious-event counts. Nor can a lack of recorded serious events in a group establish that no risk exists. The number of observed events, follow-up, event definitions, and group comparability all affect what safety counts can show. The available entries do not provide enough information for a causal safety comparison.

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

The record establishes that this was a phase 2 study of VOX plus SOF/VEL in adults with chronic non-genotype 1 HCV infection, with treatment regimens spanning 6, 8, and 12 weeks. It defines SVR12 as HCV RNA below the lower limit of quantitation 12 weeks after the last dose and names the Full Analysis Set as the primary analysis population. These details clarify what the planned primary measure represents.

However, a numerical SVR12 result is not reported in the registry record. There is no percentage, confidence interval, or endpoint-specific denominator available to characterize the observed primary outcome. The registry’s enrollment of 128 does not establish how many participants contributed to this endpoint. Consequently, the record does not support a quantitative statement about the primary response estimate or its precision.

The study’s non-randomized, sequential design also limits direct comparisons among the regimen groups. The registry describes differences in duration, treatment history, and cirrhosis status, and explicitly notes that the groups are not a like-for-like control comparison. An outcome difference across these groups, if reported elsewhere, could not automatically be attributed to the regimen itself without considering design and analysis. No adjusted comparison is reported in the registry record.

The safety entries provide a descriptive account of serious adverse events in four groups, including one recorded serious event in the 12-week treatment-experienced, cirrhotic group. They do not establish comparative safety or characterize all possible harms. Overall, the record conveys study design, endpoint definitions, and selected safety counts, but does not provide the numerical primary efficacy result or enough analysis detail to assess its statistical evidence. It does not establish a treatment effect, and it does not show that a treatment does or does not work.

14. Why This Trial Matters Statistically

Statistically, this study illustrates why an endpoint definition and a result are separate pieces of evidence. The registry specifies a clinically interpretable post-treatment endpoint, SVR12, and defines the response threshold using HCV RNA below the lower limit of quantitation. It also identifies the primary population as participants who received at least 1 dose. Those definitions help readers understand what an estimate would represent, but they cannot replace the estimate, interval, denominator, or analysis details.

The design is also important to interpretation. Sequential non-randomized groups can describe outcomes under different regimens and participant circumstances, but do not automatically provide a fair treatment contrast. Here, the arm descriptions distinguish treatment history, cirrhosis status, and treatment duration. The registry itself warns that the groups are not like-for-like controls. That makes the study a useful example of why design details should be considered before interpreting between-group outcomes as causal.

There is also a practical lesson about registry records: an outcome can be named without its numerical result being available in the record. Readers should distinguish a stated objective or outcome measure from a reported analysis. The absence of a numerical SVR12 result prevents assessment of both the response estimate and its precision, while the absence of analysis details leaves questions about missing outcomes and multiplicity unresolved.

The listed serious adverse event counts offer some descriptive safety information, but they do not overcome the limitations of the design or provide a comparative analysis. In this trial, careful statistical reading means separating what the registry defines, what it reports numerically, and what remains unreported. That distinction is central to evaluating the scope of the evidence without overstating it.

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 primary limitation for interpreting efficacy is that the registry record does not report a numerical SVR12 result, confidence interval, or endpoint-specific denominator. Although the study enrollment is listed as 128, that figure is not the analysis denominator for the primary endpoint. The Full Analysis Set is defined by receipt of at least 1 dose, but the record does not state how many participants met that definition or how many had evaluable SVR12 status.

The non-randomized, sequential design limits causal interpretation and direct comparisons among groups. The regimen descriptions vary by treatment duration, treatment history, and cirrhosis status. The record notes that the arms are not a like-for-like control comparison and does not report adjusted estimates or methods for addressing differences between groups. Open-label conduct is also recorded, while further details on outcome assessment procedures are not reported in the registry record.

The registry lists secondary outcome definitions but does not report their numerical results in the available record. It also does not report multiplicity procedures, missing-data handling, sensitivity analyses, an interim-analysis plan, or the statistical analysis plan. No sample-size justification is reported in the registry record. These omissions limit assessment of how the study was designed to estimate effects and how incomplete data or multiple outcomes may have influenced interpretation.

For safety, the listed serious adverse event counts are descriptive and cover four groups. Observation time, comparative methods, and further context for the listed gastroenteritis percentage are not reported. Death counts are not reported in the registry record. These limitations do not negate the information that is present, but they set boundaries on what can be concluded from the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of Voxilaprevir Plus Sofosbuvir/Velpatasvir Fixed Dose Combination in Adults With Chronic Non-Genotype 1 HCV Infection — NCT02378961.
• Registry record last updated 2020-03-03; status last verified 2017-10.
• Results first posted 2017-09-15.
• 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

NCT02378961 is a completed phase 2, global, multicenter, open-label, non-randomized, sequential study sponsored by Gilead Sciences. It enrolled 128 participants with chronic non-genotype 1 HCV infection. The registry records a study start date of 2015-02-16 and primary completion on 2015-09-21.

The study evaluated VOX plus SOF/VEL regimens of 6, 8, or 12 weeks across groups distinguished by treatment history and cirrhosis status. The primary outcome was the percentage with SVR12, defined as HCV RNA below the lower limit of quantitation 12 weeks after the last dose. The primary analysis population was the Full Analysis Set, defined as participants who received at least 1 dose.

A numerical primary efficacy result and its confidence interval are not reported in the registry record. The record lists secondary outcomes and descriptive serious adverse event counts, but does not report the statistical analysis plan, missing-data procedures, or multiplicity handling.