Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir Fixed-Dose Combination With or Without Ribavirin in Participants With Chronic Genotype 1 HCV Infection Previously Treated With a Direct Acting Antiviral Regimen: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir Fixed-Dose Combination With or Without Ribavirin in Participants With Chronic Genotype 1 HCV Infection Previously Treated With a Direct Acting Antiviral Regimen (NCT02536313), a randomized phase 2 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Cessation of Treatment (SVR12).

2. Clinical Question

The clinical question concerns response after prior direct-acting antiviral treatment, rather than response in an HCV population without that treatment history. The primary endpoint is reported separately for the two treatment groups. The registry record does not report a formal statistical comparison of the groups for the primary endpoint, so the percentages and confidence intervals should be read as group-specific estimates rather than as evidence of a tested difference between regimens.

The study also registered secondary outcomes concerning response at other post-treatment times, HCV RNA during treatment, change in HCV RNA, and virologic failure. Those outcomes provide additional descriptions of the treatment course and follow-up, but their role in drawing conclusions depends on their reported results and on the analysis plan, which is not reported in the registry record.

3. Trial Design

This was a phase 2, randomized, open-label, parallel-group study. The registry lists 49 participants enrolled: 24 in the SOF/VEL/VOX group and 25 in the SOF/VEL/VOX plus ribavirin group. Both regimens were specified for 12 weeks. Because the study was open-label, masking was listed as none.

The registry describes participants as having chronic genotype 1 HCV infection and prior treatment experience with a direct-acting antiviral regimen. The primary outcome population was the Full Analysis Set, defined in the record as all randomized or enrolled participants who took at least one dose of study drug. The reported group denominators for SVR12 are 24 and 25, matching the enrollment counts listed for the arms.

The primary endpoint was the percentage of participants with SVR12, assessed at post-treatment week 12. The registry also lists secondary outcomes including SVR at post-treatment weeks 4 and 24, HCV RNA below the lower limit of quantitation on treatment, change in HCV RNA from baseline or day 1 through week 12, and virologic failure through post-treatment week 24.

The study status is completed. The registry lists a start date of 2015-07-29 and primary completion on 2016-03-28. These administrative details describe the recorded study timeline, but do not supply further information about recruitment procedures, follow-up completeness, or how individual outcomes were analyzed.

The registry record does not report the allocation sequence method, a sample-size justification, prespecified interim analyses, or a detailed statistical analysis plan. It also does not report whether the study was designed to test superiority, equivalence, or non-inferiority between the regimens. The randomized design establishes the intended treatment-group comparison, but the absence of these details limits what can be inferred about the design’s statistical objectives.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: all randomized/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: participants who took 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 Cessation of Treatment (SVR12), measured over Posttreatment Week 12.

The primary endpoint is the percentage of participants with sustained virologic response 12 weeks after treatment cessation, called SVR12. The registry defines a response as HCV RNA below the lower limit of quantitation, specified as 15 IU/mL, at post-treatment week 12. The reported endpoint is therefore a binary classification for each participant: the threshold was or was not met at the stated follow-up.

SVR12 is used as a follow-up measure of virologic response after the treatment course has ended. Measuring the outcome after treatment distinguishes it from an on-treatment laboratory response and places emphasis on whether HCV RNA remains below the stated threshold at the follow-up visit. The registry also lists SVR at other post-treatment times as secondary outcomes, but SVR12 is the designated primary outcome.

The registry reports a percentage and a 95% confidence interval for each treatment group. The interval conveys uncertainty around the group-specific percentage: narrower intervals generally indicate greater precision, while wider intervals indicate less precision. It does not by itself establish whether the regimens differ. That requires a direct comparison and an appropriate analysis; a formal primary-endpoint comparison is not reported in the registry record.

The endpoint population is defined as randomized or enrolled participants who received at least one dose of study drug. This definition makes treatment exposure part of inclusion in the primary analysis population. The registry record does not describe how missing post-treatment HCV RNA measurements were handled, so the percentages should be interpreted with that reporting limitation in mind.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain how to read the posted results. The central distinction is between describing the outcomes observed in each group and estimating a treatment-group contrast. The registry reports group-specific SVR12 percentages and confidence intervals. It also reports a comparison for the secondary virologic-failure outcome. These are different kinds of statistical summaries and should not be treated as interchangeable.

What does a confidence interval convey?

A confidence interval describes uncertainty around an estimate under the statistical method used to construct it. For SVR12, each group has its own interval around its percentage. The interval is not a range containing a fixed proportion of individual participant outcomes, and it is not a guarantee that the true value lies within those limits. It is a way of expressing how much uncertainty accompanies an estimate from a finite group of participants.

The primary-endpoint intervals are relatively broad in relation to the observed percentages. That matters because a point estimate alone can look more certain than the data warrant. The lower and upper limits show that values meaningfully below the point estimate remain compatible with the data and the interval method. The registry does not name the interval-construction method, so a more specific account of its assumptions is not reported in the registry record.

Why is a direct comparison different?

Two separate group estimates do not, by themselves, answer whether the groups differ. A direct comparison estimates a contrast, such as a risk difference, and quantifies uncertainty around that contrast. For the primary SVR12 endpoint, the registry reports no such comparison. Thus, the endpoint results support a descriptive account of response in each group, but not a formal inference about the difference between regimens.

For virologic failure, the record gives a risk difference estimate and a confidence interval. Because the interval includes zero, the data are compatible with no difference as well as with effects in either direction under that method. The unadjusted p-value is 0.322. A p-value summarizes how unusual data at least as discrepant as those observed would be under a specified null model; it is not the probability that the null hypothesis is true, nor a measure of clinical importance. The registry does not report adjustment for multiple testing for this secondary comparison.

How should small event counts be read?

Binary outcomes such as SVR12 and virologic failure classify participants according to whether an event or response occurred. With relatively few participants, each participant represents a meaningful part of the group’s observed percentage. When events are rare, a risk difference can be especially imprecise because the estimate is based on very few observed events. This is one reason the virologic-failure comparison has limited precision and should be interpreted cautiously.

For continuous outcomes, such as change in HCV RNA, statistical summaries may describe a mean or another location measure and its variability. The registry lists HCV RNA change as a secondary outcome but does not include its numerical result in the record summarized for this analysis. Distributional assumptions, transformations, and handling of values below quantitation are not reported in the registry record.

What does randomization contribute?

Random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline factors. It does not guarantee exact balance in a small study. The registry identifies the allocation as randomized, but it does not describe sequence generation, concealment, stratification, or other implementation details. Randomization supports the intended comparison, while the missing implementation information limits assessment of how it was carried out.

Open-label status means masking was listed as none. Knowledge of treatment assignment can influence behaviors and assessments, especially when outcomes involve subjective judgments. The primary endpoint is based on a laboratory threshold, which is less dependent on subjective rating than many clinical outcomes, but open-label conduct can still matter for follow-up and other aspects of trial delivery. The registry does not report whether laboratory assessment was masked.

What do planning illustrations mean?

Sample-size planning illustrations based on an observed effect are not observed power and are not evidence that the study was adequately sized for its original purpose. Such illustrations depend on stated assumptions, including the effect chosen to detect, significance level, allocation, and statistical approximation. The record describes an illustration using a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. The registry does not report that these were the trial’s original design assumptions or provide a sample-size justification.

Planning calculations translate assumptions into a prospective design illustration. They do not change the uncertainty in the actual trial estimates, and they cannot repair an absent primary comparison. The registry record does not report an interim-analysis plan, stopping rule, or detailed analysis plan. These omissions mean the intended control of error rates and the prespecified status of particular analyses cannot be assessed from the record.

Why does multiplicity matter?

When a study assesses several outcomes or performs several comparisons, the chance of at least one apparently notable result can increase if each is interpreted without regard to the others. A prespecified hierarchy, adjustment, or other strategy can address this issue, depending on the study’s goals. The registry lists multiple secondary outcomes, but a multiplicity strategy is not reported. Accordingly, unadjusted secondary findings should be viewed as exploratory or supportive rather than as stand-alone confirmatory evidence.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes, but it does not report a multiplicity strategy. When multiple outcomes are analyzed, unadjusted statistical tests can increase the chance of a nominally notable finding across the set of analyses. Approaches such as a prespecified testing hierarchy or adjustment can help control that issue, but no such approach is described in the registry record. The unadjusted virologic-failure comparison should therefore be regarded as limited secondary evidence rather than a confirmatory finding.

Missing-data handling is also not reported. The primary analysis population is defined as randomized or enrolled participants who took at least one dose of study drug, but the record does not state how participants without an SVR12 measurement were treated, whether imputation was used, or how withdrawals and incomplete follow-up were addressed. The reported denominators match the arm enrollment counts, but that alone does not establish that every participant had an observed outcome or explain any missing observations.

The Full Analysis Set definition includes treatment exposure, so it is not a statement that every randomized participant was analyzed regardless of whether treatment began. The registry does not provide a participant flow description sufficient to assess exclusions after randomization, adherence, or follow-up completeness. These details matter because conclusions can be sensitive to how incomplete outcome data are handled, particularly in a small study.

The record does not report the detailed statistical analysis plan, the primary endpoint’s comparison model, the method used to construct the primary confidence intervals, or whether any interim analyses were conducted. It also does not report a sample-size justification for the trial’s intended comparison. Without those details, the planned inferential framework and the handling of multiple looks or outcomes cannot be verified from the registry record.

These are reporting limitations, not proof that the study lacked procedures or that data were missing. The appropriate conclusion is narrower: the registry record does not describe the procedures, so their effects on interpretation cannot be evaluated. The group-specific estimates and reported secondary comparison remain readable, but precision and inferential claims should reflect these unresolved details.

11. 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: pneumonia (4.2%).

The registry lists serious adverse events for each treatment group as counts among participants at risk: one serious event among 24 participants receiving SOF/VEL/VOX and none among 25 receiving SOF/VEL/VOX plus ribavirin. No deaths are reported in either group. Pneumonia is listed as a top serious adverse event term at 4.2%, but the record does not identify which treatment group that term belongs to.

These counts are sparse and should be treated as descriptive. They do not provide a precise estimate of comparative safety, and they do not establish that serious events are more or less likely with either regimen. With few events, estimates of event frequency are uncertain; the absence of a recorded event in a group does not establish that the underlying risk is zero.

The registry also lists other adverse events affecting 6 of 24 participants in the SOF/VEL/VOX group and 11 of 25 participants in the combination group. These counts concern a different category from serious adverse events and should not be conflated with the serious-event counts. The record does not report event-level details, attribution to study treatment, timing, severity grading beyond the serious classification, or exposure-adjusted summaries. The safety figures therefore offer a limited description rather than a complete comparative safety assessment.

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

The primary result describes SVR12 percentages in two groups of participants with chronic genotype 1 HCV infection and prior direct-acting antiviral treatment. The estimates are accompanied by confidence intervals, which convey uncertainty. They do not establish the exact response percentage that would be expected in a broader population, and they do not by themselves demonstrate a treatment-group difference.

The registry record does not report a formal primary-endpoint comparison, nor does it identify a superiority, equivalence, or non-inferiority objective. Therefore, the results cannot support a claim that one regimen is statistically better, that the regimens are equivalent, or that one is non-inferior to the other. Similar-looking group percentages are not a substitute for a prespecified comparison with an appropriate uncertainty assessment.

The trial is also limited in scale and phase. Its group sizes are 24 and 25, and the confidence intervals show that the estimates are not highly precise. The findings describe the enrolled participants and the recorded follow-up; broader generalization depends on how well those participants represent other settings and populations, information not established by the outcome percentages alone.

The secondary virologic-failure result is based on very few events and is reported with an unadjusted p-value. It should not be treated as a definitive safety or efficacy conclusion, especially in the absence of a reported multiplicity strategy. Other registered secondary outcomes are not numerically reported in the registry record, limiting their ability to reinforce or challenge the primary pattern.

The safety counts are similarly descriptive. One serious event in one group, none in the other, and no deaths do not provide a precise comparison of risks. The record also lacks detail on event relatedness and timing. These data neither prove a safety advantage nor rule out uncommon harms.

In short, the posted data provide a snapshot of outcomes in a small randomized study, with high observed SVR12 percentages and notable statistical uncertainty. They do not establish comparative effectiveness or comprehensive safety, and they do not replace evidence from a prespecified inferential analysis or a broader evidence base.

13. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between a strong-looking point estimate and a precise estimate. The observed SVR12 percentages are high in both groups, yet the confidence intervals remain wide. A point estimate can convey the observed sample result; its interval communicates how much uncertainty remains when generalizing beyond those participants.

It also highlights that a randomized design does not guarantee that the registry will report an inferential comparison for every endpoint. The primary endpoint is presented by group, but a formal comparison is not reported. Without that contrast, readers should not convert a descriptive pattern into a claim that one regimen is superior or that the groups are equivalent. The study’s randomization is relevant, but the analysis reported still determines which statistical questions can be answered.

The secondary virologic-failure comparison further illustrates the limits of sparse events. When events are few, the estimated contrast is uncertain, and an unadjusted p-value must be read in the context of multiple registered outcomes. It is possible to report a numerical comparison without that comparison providing firm evidence for a treatment effect.

Finally, the registry’s definition of the primary analysis population and its lack of reporting on missing-data handling, multiplicity, and the detailed analysis plan show why endpoint estimates need design context. Statistical interpretation depends not only on the observed percentages, but also on who was analyzed, how uncertainty was calculated, and which analyses were prespecified. Those details are not reported in the registry record, so the most reliable reading remains appropriately descriptive.

14. 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.

Several limitations are specific to the information recorded for this trial. The study enrolled 49 participants across two groups, so the primary estimates and especially rare-event summaries have limited precision. The primary SVR12 confidence intervals are broad, and the registry record does not provide a formal comparison between groups for that endpoint.

The trial was open-label, with masking listed as none. Although the primary endpoint is based on HCV RNA, knowledge of assignment could affect behavior, reporting, or follow-up processes. The record does not state whether laboratory assessment was masked or describe safeguards against such influences.

The analysis population is defined as participants who received at least one dose, but participant flow and missing outcome handling are not reported. It is therefore not possible to assess from the registry record whether all randomized or enrolled participants contributed an observed SVR12 result, or how incomplete follow-up affected the estimates.

The record does not report the allocation sequence method, concealment procedures, the trial’s sample-size justification, a detailed analysis plan, or any interim-analysis procedures. It also does not describe a multiplicity strategy despite listing several secondary outcomes. These gaps make it difficult to evaluate whether the reported analyses reflect prespecified decisions and how the overall chance of false-positive findings was managed.

Secondary numerical reporting is incomplete in the registry record summarized for this analysis. The reported virologic-failure comparison is unadjusted and based on few events. The safety information is also limited to counts and a top serious-event term, without details about timing, treatment relationship, or event-level descriptions. These limitations do not show that the findings are invalid; they constrain the strength and scope of conclusions that can be drawn from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir Fixed-Dose Combination With or Without Ribavirin in Participants With Chronic Genotype 1 HCV Infection Previously Treated With a Direct Acting Antiviral Regimen — NCT02536313.
• Registry record last updated 2019-02-25; status last verified 2017-08.
• Results first posted 2017-09-14.
• 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.

18. Record Summary

NCT02536313 is a completed randomized, open-label, parallel-group phase 2 study sponsored by Gilead Sciences. It enrolled 49 participants with chronic genotype 1 HCV infection previously treated with a direct-acting antiviral regimen. Participants received SOF/VEL/VOX or SOF/VEL/VOX plus ribavirin for 12 weeks.

The primary endpoint was SVR12, defined as HCV RNA below 15 IU/mL at post-treatment week 12. The registry reports 100.0% among 24 participants in the SOF/VEL/VOX group and 96.0% among 25 participants in the combination group, with group-specific 95% confidence intervals. A formal primary-endpoint comparison is not reported.

Registered secondary outcomes cover additional response times, on-treatment HCV RNA, HCV RNA change, and virologic failure. A secondary virologic-failure comparison is reported, but it is unadjusted and imprecise. Serious adverse event counts were low, with no deaths reported. The registry record does not report the detailed statistical plan, missing-data procedures, or multiplicity strategy.