Efficacy And Safety Of Sofosbuvir/Velpatasvir Fixed Dose Combination With Ribavirin in Chronic HCV Infected Adults Who Participated in a Prior Gilead Sponsored HCV Treatment Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy And Safety Of Sofosbuvir/Velpatasvir Fixed Dose Combination With Ribavirin in Chronic HCV Infected Adults Who Participated in a Prior Gilead Sponsored HCV Treatment Study (NCT02300103), a na 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 clinical question is about the observed response after a 24-week course in a specific group: adults who had previously taken part in a Gilead-sponsored HCV treatment study and did not achieve SVR there. It is not a head-to-head question about whether this regimen performs better than another regimen, because the study has one treatment group and no comparator arm.

The registry describes a phase 2 study with 69 enrolled participants. Its primary objective also refers to safety and tolerability, and the posted outcomes include measures beyond SVR12. However, the numerical primary outcome result is not reported in the registry record. The record therefore defines the question and population but does not provide the primary estimate needed to summarize the observed SVR12 percentage or its precision.

3. Trial Design

This is a completed phase 2, open-label, single-group study sponsored by Gilead Sciences. The registry lists 69 participants as enrolled. Participants received SOF/VEL fixed-dose combination with RBV for 24 weeks. The study began on 2014-12-01, had a primary completion date of 2016-07-02, and is listed as completed.

Because there is one treatment group and no comparator arm, the design does not provide a randomized, concurrent contrast between regimens. The allocation field is listed as not applicable, and masking is listed as none. The study is described as open label, so the registry does not indicate that treatment assignment was concealed from participants or investigators. The record does not report a separate control group or a comparison against an alternative treatment.

The target group is also specific to treatment history: participants had chronic HCV infection and had taken part in a prior Gilead-sponsored HCV treatment study without achieving SVR. These eligibility details matter when considering how broadly the findings might apply. The record does not provide further details about the prior treatment regimens or the composition of the enrolled group.

The primary outcome is SVR12, assessed after treatment, and the primary outcome population is described as all enrolled participants who received at least one dose of study drug. The registry also lists outcomes for SVR4 and SVR24, on-treatment HCV RNA below the lower limit of quantitation, change in HCV RNA from baseline, and virologic failure. It lists six outcome measures and zero analyses. Additional details about the statistical plan, sample-size justification, or conduct of any interim analyses are 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: 74 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: all enrolled participants who received at least one 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 (SVR12). The registry defines SVR12 as HCV RNA below the lower limit of quantitation 12 weeks following the last dose of study drug. The outcome is therefore a binary status for each participant at a specified post-treatment time point, summarized as a percentage for the study population.

In general, a post-treatment virologic endpoint is used to describe whether the measured virus level remains below a stated threshold after treatment has ended. A fixed assessment time makes the endpoint more clearly defined than an unspecified follow-up measure. The threshold and timing are part of the endpoint definition; they do not, by themselves, reveal how many participants met the definition.

The registry identifies the primary analysis population as the Full Analysis Set: all enrolled participants who received at least one dose of study drug. The primary outcome is listed with a 95% confidence interval as its dispersion measure. However, the numerical percentage and confidence interval are not reported in the registry record. Thus, readers can identify what was intended to be measured and in whom, but cannot assess the observed response level or its statistical precision from the registry information.

The listed secondary outcomes include SVR4 and SVR24, on-treatment HCV RNA below the lower limit of quantitation, HCV RNA change from baseline, and virologic failure. Their numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a percentage of participants and lists a 95% confidence interval. This is consistent with summarizing a binary endpoint: each participant either meets the SVR12 definition or does not, and the group result is expressed as a percentage. The registry does not give the observed percentage or its interval, and it does not describe the method used to calculate the interval.

What does a confidence interval communicate?

In general, a confidence interval expresses uncertainty in an estimate. It gives a range of values compatible with the observed data under the interval's statistical procedure. The width is informative about precision: a wider interval reflects more uncertainty than a narrower one. A 95% confidence interval is not a guarantee that the true value lies within the particular interval, nor does it describe the range of individual participant outcomes. In this record, the confidence interval is named as the dispersion measure, but the actual interval and its calculation method are not reported in the registry record.

What does the single-group design mean for analysis?

The study has one group receiving SOF/VEL with RBV. In general, a single-group summary can describe the outcomes observed among participants who received the regimen, but it does not create a randomized contrast with a control group. Differences from external expectations or other studies would not be randomized comparisons. The registry record does not report such a comparative analysis, and it does not give an analysis plan that would explain any adjustment for outside factors.

The primary outcome population is stated as the Full Analysis Set, defined as all enrolled participants who received at least one dose of study drug. That definition specifies who is intended to contribute to the primary outcome summary. It does not, by itself, tell readers how many participants had an evaluable SVR12 assessment, how missing measurements were handled, or whether any participants were excluded from the outcome calculation. Those details are not reported in the registry record.

How should the other outcome measures be understood?

The listed secondary outcomes cover additional time points and types of measurement: SVR4 and SVR24, HCV RNA below the lower limit of quantitation during treatment, change in HCV RNA from baseline, and virologic failure. These outcomes address different aspects or timings of virologic response. In general, multiple outcomes can provide a broader description of a study, but they also raise questions about how results are prioritized and how the chance of false-positive findings is managed. The registry does not report a multiplicity strategy or numerical results for these secondary outcomes.

The registry lists six outcome measures and zero analyses. This means that the record identifies outcomes but does not attach analysis entries in the information. It does not establish what analyses may have been conducted outside the registry entry. The statistical analysis plan, including any planned models, covariate adjustments, interim analyses, or rules for handling missing data, is not reported in the registry record.

How should planning illustrations be read?

The sample-size section is a planning illustration based on the observed effect, rather than a description of the trial's original design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. The illustration reports participants per arm for non-time-to-event outcomes; time-to-event tables report total events.

These assumptions do not match the trial's single-group structure, so the illustration should not be mistaken for the study's enrolled sample size, an original design justification, or a direct account of how this trial was analyzed. In general, such calculations depend on their assumptions and are planning aids. They are not observed power, and they do not show the probability that a result from this completed study is true. The registry does not report the trial's own sample-size justification or statistical plan.

Finally, the registry provides a primary endpoint definition and a stated confidence-interval format, but not the numerical primary result, its denominator at assessment, or the calculation details. The distinction between knowing what was planned to be measured and seeing the measured result is central to reading this record: the former is documented, while the latter is 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+RBV")
n      <- c(69)
events <- c(63)
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+RBV  69  63  91.3  82.0  96.7  82.3  96.0  82.3  95.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary SVR12 outcome and several secondary outcomes, including SVR4, SVR24, on-treatment HCV RNA below the lower limit of quantitation, HCV RNA change from baseline, and virologic failure. When a study evaluates several outcomes or time points, multiplicity can matter: in general, examining multiple results can increase the chance of finding an apparently notable result by chance. A prespecified strategy may address that issue, but a multiplicity adjustment or testing hierarchy is not reported in the registry record.

The record identifies the primary outcome population as all enrolled participants who received at least one dose of study drug. It does not state how participants without an SVR12 measurement were handled, whether any outcome data were imputed, or how missing assessments affected the denominator. These missing-data procedures are not reported in the registry record. The endpoint population definition should therefore not be taken as a complete account of the analysis rules.

The registry lists six outcome measures and zero analyses. It gives the primary endpoint's confidence-interval format but not a numerical result or the method used to calculate it. The statistical analysis plan, including any planned interim analyses, is not reported in the registry record. These omissions limit independent assessment of which analyses were prespecified and how uncertainty or multiple outcomes were handled.

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: nephrolithiasis (1.4%).

The safety figures are reported for the SOF/VEL+RBV group. The registry lists 69 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it lists 69 at risk and 55 affected. The recorded number of deaths is 0. Nephrolithiasis is listed among the serious adverse event terms at 1.4%.

These are descriptive counts for the study group, not a comparison between treatment groups. In general, a count of participants affected does not convey how long each person was observed, the severity or duration of every event, or whether an event was caused by study treatment. The registry figures also do not provide a full account of event timing or individual clinical circumstances. The term “at risk” identifies the group size shown for each safety category; the listed counts should be read within that reporting framework.

The serious-event and other-event figures are separate summaries and should not be combined. The registry does not report a control group or comparative safety analysis. These figures therefore describe reported safety events in the treated group, without establishing a relative difference in risk.

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

The record establishes that this completed phase 2 study evaluated SOF/VEL with RBV for 24 weeks in adults with chronic HCV infection who had participated in a prior Gilead-sponsored HCV treatment study and did not achieve SVR. It specifies SVR12 as the primary endpoint and defines the outcome as HCV RNA below the lower limit of quantitation 12 weeks after the last dose. It also describes the primary analysis population and reports selected safety counts.

However, the primary SVR12 percentage and its 95% confidence interval are not reported in the registry record. The record therefore does not show how many participants met the primary endpoint as a percentage, or how precisely that percentage was estimated. Numerical findings for the listed secondary outcomes are also not reported in the registry record. The design and outcome definitions cannot substitute for those results.

The study's single-group design does not provide a concurrent randomized comparison. Thus, the posted information cannot show a comparative treatment effect against another regimen. The safety counts likewise describe the treated group and do not establish whether event rates differ from those under another treatment.

In general, an endpoint result describes what was observed in a study population, while a comparative claim requires an appropriate comparison and analysis. Even a reported response percentage would need to be read in light of the population, endpoint timing, uncertainty, missing-data handling, and design. Here, some of those elements are described, but the primary numerical result and several analysis details are absent. The appropriate reading is therefore limited to the documented study question, design, endpoint definition, and reported safety summaries—not an inference about efficacy or comparative benefit.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a well-defined clinical question and an unavailable numerical primary result. The registry describes the population, regimen, endpoint timing, and endpoint threshold, and it identifies the analysis population. Those details allow readers to understand what the study set out to assess. But without the SVR12 percentage and confidence interval, readers cannot quantify the primary outcome or its precision from the registry record.

The single-group structure is another important statistical feature. It can support a descriptive summary of outcomes among participants in the study, but it does not provide a randomized comparison with another treatment. That distinction matters when interpreting any apparent response: a descriptive result and a comparative treatment effect answer different questions. In this record, the primary descriptive result itself is not reported.

The study also illustrates why the outcome definition and analysis population need to be considered alongside the estimate. SVR12 is tied to a specific post-treatment time and a stated HCV RNA threshold, while the Full Analysis Set includes enrolled participants who received at least one dose. The registry does not explain missing-data handling or provide the number assessed at the primary time point, so the denominator and analysis details cannot be independently reviewed.

Finally, the planning illustrations should be kept separate from the trial's design and observed results. Their stated assumptions include equal allocation between two arms, even though this study is single group. They are planning illustrations, not evidence of observed power or a substitute for the registry's missing primary estimate. Together, these features make this record a useful example of how design, endpoint definition, analysis transparency, and result reporting each contribute to statistical interpretation.

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 central limitation of interpreting this trial from the registry record is that the numerical primary endpoint result is not reported. Although the record specifies SVR12 and lists a 95% confidence interval as the dispersion measure, it does not provide the percentage or interval. Numerical results for the listed secondary outcomes are also not reported in the registry record. This prevents assessment of the observed response level and the precision of the efficacy estimate.

The single-group design has no concurrent comparator. It therefore cannot provide a randomized comparison with another regimen. The population is also specific: participants had chronic HCV infection and had not achieved SVR in a prior Gilead-sponsored HCV treatment study. Further participant characteristics and details of previous treatment are not reported, limiting assessment of how results might relate to other populations.

The registry defines the Full Analysis Set as enrolled participants who received at least one dose, but does not report the number with an evaluable SVR12 assessment, the handling of missing outcome data, or exclusions from the primary analysis. The statistical analysis plan, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record. Although safety counts are listed, comparative safety information is unavailable because there is no control group. These limitations describe what cannot be assessed from this record; they do not establish that any particular analysis or procedure was or was not conducted outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy And Safety Of Sofosbuvir/Velpatasvir Fixed Dose Combination With Ribavirin in Chronic HCV Infected Adults Who Participated in a Prior Gilead Sponsored HCV Treatment Study — NCT02300103.
• Registry record last updated 2018-11-16; status last verified 2017-06.
• Results first posted 2017-07-28.
• 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

This completed phase 2 study enrolled 69 adults with chronic HCV infection who had participated in a prior Gilead-sponsored HCV treatment study and did not achieve SVR. It evaluated SOF/VEL fixed-dose combination with RBV for 24 weeks in an open-label, single-group design without a comparator arm.

The primary outcome was SVR12, defined as HCV RNA below the lower limit of quantitation 12 weeks after the last dose. The primary analysis population was all enrolled participants who received at least one dose of study drug. The numerical primary outcome and its 95% confidence interval are not reported in the registry record.

The registry lists secondary virologic outcomes and safety summaries, including 1 participant affected by a serious adverse event, 55 affected by other adverse events, and 0 deaths. Nephrolithiasis is listed among serious adverse event terms at 1.4%. Details of the statistical plan, missing-data handling, and multiplicity procedures are not reported in the registry record.