Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection in Participants With Chronic Genotype 1, 2, 3, or 6 HCV Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection in Participants With Chronic Genotype 1, 2, 3, or 6 HCV Infection (NCT01826981), a 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

3. Trial Design

The registry identifies this as a Phase 2, multicenter, randomized, open-label study with a parallel-group model. It was designed to assess the efficacy and safety of sofosbuvir-containing regimens for chronic HCV infection. The record reports enrollment of 359 and an overall study status of completed. Study start is listed as 2013-04 and primary completion as 2015-03.

The trial included six cohorts and multiple groups. Regimens and eligibility characteristics varied: some groups were for participants who had not achieved SVR in a previous Gilead sofosbuvir study; others involved treatment-experienced participants with liver disease, treatment-naive participants, participants with cirrhosis, or participants with HCV and HBV coinfection. Genotypes 1, 2, 3, and 6 were represented. Regimens included different combinations of sofosbuvir, ledipasvir, velpatasvir, ribavirin, peginterferon, and GS-9669, with treatment durations of 8, 12, or 24 weeks depending on the group.

Randomized allocation is reported for the study as a whole, but the listed arms do not all represent a like-for-like treatment contrast. For example, a treatment-naive genotype 3 group and a retreatment group differ in eligibility as well as regimen. The arm-level percentages therefore describe results within groups with differing clinical characteristics; they should not automatically be interpreted as a common randomized comparison across every listed regimen. The posted comparisons use one group as a reference, but the registry record does not report a sponsor analysis for those contrasts.

The primary analysis population is described as the full analysis set: participants who were randomized and received at least 1 dose of study drug. Details of any additional analysis populations, exclusions after randomization, or handling of missing primary-outcome data 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: 446 participants were screened.

Only the first 6 of 15 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set: Participants who were randomized 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: Participants who were randomized and received at least 1 dose of study drug.

Only the first 6 of 16 groups are shown.

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 is defined in the registry as HCV RNA below the lower limit of quantification at post-treatment week 12. The endpoint is assessed after treatment has ended, so it captures whether the specified virologic threshold was met at a follow-up time rather than only during therapy.

In general, a post-treatment response measure is useful because an on-treatment viral result alone does not establish that the response persists after treatment stops. SVR12 provides a defined follow-up point for describing post-treatment virologic status. The registry also lists outcomes for viral RNA during treatment and at other post-treatment times, as well as on-treatment virologic failure and viral relapse. Those measures address related but distinct parts of the treatment course; they do not replace the primary endpoint’s particular timing and definition.

The endpoint is reported as a percentage of participants, and the primary population includes randomized participants who received at least 1 dose of study drug. The posted results vary across groups, from 64.0% in the treatment-naive genotype 3 LDV/SOF group to 100.0% in several groups. These are cohort-specific observed percentages. The registry record does not report confidence intervals for the individual arm percentages, and it does not report the number of participants with missing SVR12 data or the method used to handle missing values.

SVR12 is a virologic outcome. It does not, by itself, describe every aspect of health, safety, durability beyond the reported follow-up, or comparative performance in populations not included in a particular group.

7. Results Posted in the Registry

• Cohort 1,Group 2: SOF+Peg+RBV 12 wk (GT2,3 SOF Retreatment): 90.0% (9/10) versus 100.0% (19/19) on control; risk difference -10.0 percentage points (95% CI -28.6 to 8.6), risk ratio 0.90 (0.73–1.11); unadjusted two-proportion z-test p = 0.161.
• Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, Liver Disease): 100.0% (25/25) versus 100.0% (19/19) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.
• Cohort 2,Group 2: LDV/SOF+GS-9669 12 wk (GT1 TE, Liver Disease: 100.0% (26/26) versus 100.0% (19/19) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0), risk ratio 1.00 (1.00–1.00); unadjusted two-proportion z-test p = n/a.
• Cohort 2,Group 3: LDV/SOF 12 wk (GT3 TN): 64.0% (16/25) versus 100.0% (19/19) on control; risk difference -36.0 percentage points (95% CI -54.8 to -17.2), risk ratio 0.64 (0.48–0.86); unadjusted two-proportion z-test p = 0.003.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants Experiencing Viral Relapse

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Cohort 1,Group 2: SOF+Peg+RBV 12 wk (GT2,3 SOF Retreatment): 10.0% (1/10) versus 0.0% (0/19) on control; risk difference 10.0 percentage points (95% CI -8.6 to 28.6); unadjusted two-proportion z-test p = 0.161.
  • Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, Liver Disease): 0.0% (0/25) versus 0.0% (0/19) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort 1,Group 2: SOF+Peg+RBV 12 wk (GT2,3 SOF Retreatment) and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cohort 2,Group 1: LDV/SOF+RBV 12 wk (GT 1 TE, Liver Disease) and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes describe different points in the virologic course: HCV RNA while treatment is ongoing, response at several post-treatment follow-up times, on-treatment virologic failure, and viral relapse. Together, these outcomes can add context to the primary SVR12 measure by showing whether viral suppression was recorded during therapy and how post-treatment results were characterized at other times. They are related to SVR12, but each has its own timing and definition; none should be treated as interchangeable with the primary endpoint.

The posted viral-relapse percentages vary across groups, including groups with no recorded relapse and groups with nonzero percentages. These results do not independently resolve why SVR12 differs across cohorts. Relapse is only one possible component of a post-treatment outcome pattern, and interpretation also depends on the underlying analysis population, available follow-up, and the registry’s definitions. Details about missing measurements and the handling of participants without follow-up results are not reported in the registry record.

Secondary outcomes are generally less definitive than a prespecified primary endpoint when many outcomes or comparisons are assessed. In general, testing multiple outcomes increases the chance of finding an apparently unusual result even when no underlying difference exists. An adjustment strategy or a testing hierarchy can address some of this issue, but a multiplicity plan is not reported in the registry record. The registry also reports no sponsor analyses for the posted results.

Accordingly, the secondary outcomes are best used as descriptive context for the primary SVR12 findings, not as independent confirmation of a treatment effect. Their interpretation should account for distinct measurement times, group differences, and the absence of reported multiplicity procedures and missing-data details. No single secondary result can make the cross-cohort comparisons equivalent to a direct randomized comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment
• Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment
• Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment
• Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment
• Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) While on Treatment
• Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR 24)
• For Cohort 6, Percentage of Participants With HCV RNA < LLOQ (15 IU/mL) at 16 and 20 Weeks After Discontinuation of Therapy (SVR16 and SVR 20)
• Percentage of Participants With On-treatment Virologic Failure

9. Statistical Interpretation

10. Statistical Methods Explained

Statistical interpretation depends on distinguishing the observed arm percentages from the recalculated comparisons. The posted primary outcome is binary at the participant level: a participant either met the SVR12 definition or did not, according to the registry’s stated threshold and follow-up time. The arm percentage describes the proportion meeting that definition in the analysis population. It is a summary of observed participants, not a direct measurement of certainty about the response rate in a broader population.

What does a risk difference describe?

In general, a risk difference subtracts one group’s event proportion from another group’s event proportion. For these posted recalculations, the reference is the first genotype 1 retreatment group, with LDV/SOF plus RBV for 12 weeks. A negative SVR12 risk difference means the other group’s observed percentage is lower than the reference group’s observed percentage; a positive difference would mean it is higher. A risk difference is expressed on the proportion scale and is often easier to interpret as an absolute contrast than a relative measure.

These calculations are unadjusted. They do not account for differences in participant characteristics, cohort eligibility, genotype, prior treatment, liver status, or other factors. In addition, the reference group and the comparison groups are not all described as having the same clinical profile. The calculations therefore provide a simple numerical contrast, not a substitute for a prespecified, appropriately controlled analysis. The registry record reports no sponsor analysis for these comparisons.

How should a p-value be read?

In general, a p-value describes how compatible data are with a specified null model, under the assumptions of the statistical test used. It is not the probability that a treatment works, that a result is due to chance, or that the null hypothesis is true. A smaller p-value does not indicate the size or clinical importance of a difference. It also does not address whether the comparison was planned, whether groups were comparable, or whether the test assumptions are suitable.

The listed p-values are unadjusted recalculations, and the registry record does not report the test method used for them. Because multiple groups and outcomes are present, individual p-values should be interpreted in the context of multiplicity and the overall study design. The record does not report a multiplicity adjustment or a prespecified testing hierarchy. A result that meets a conventional threshold in an unadjusted calculation should not automatically be treated as confirmatory.

Why can estimates at the boundary be difficult?

General statistical principle: binary outcomes can produce boundary estimates when every observed participant in a group has the outcome, or when none does. In this study, several groups have an observed SVR12 percentage of 100.0%. Where both the reference and comparison group have that value, the recalculated contrast is zero and the displayed interval has no width. That result describes the observed samples and the calculation used; it does not show that the population response rates are known exactly. Small samples and sparse outcomes can make uncertainty difficult to represent with simple methods.

What does the analysis population mean?

The primary endpoint population is defined as the full analysis set, consisting of randomized participants who received at least 1 dose of study drug. This definition is relevant because the denominator used for an outcome can affect the percentage. The record does not say how participants with missing SVR12 measurements were handled, whether any participants were excluded from particular outcome calculations, or whether sensitivity analyses were conducted. Those details are not reported in the registry record, so the percentages should be interpreted with that limitation in mind.

Why do randomization and open-label status both matter?

In general, random allocation can help balance measured and unmeasured characteristics between groups assigned within a trial comparison. Open-label status means participants and study personnel were not masked to treatment assignment. For an outcome based on laboratory HCV RNA, the outcome definition is objective, but open-label conduct can still matter for study procedures, treatment management, follow-up, and other outcomes. The record gives the overall allocation and masking characteristics but does not provide enough detail to determine how randomization was implemented within every cohort or how it relates to each posted contrast.

Finally, the trial’s Phase 2 status and the range of regimens and clinical groups frame the purpose of the results. The registry record does not report a sample-size justification, interim analyses, or a complete statistical analysis plan. Those omissions limit assessment of design assumptions and of how the posted analyses relate to any prespecified plan.

11. Confidence Intervals and Precision

A confidence interval describes a range of values compatible with the observed data under a statistical procedure and its assumptions. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision. An interval does not guarantee that the true value lies within its endpoints, and it does not measure the clinical importance of an estimate.

The registry record does not report confidence intervals for the individual arm-level SVR12 percentages. This matters because the percentages alone do not show how precisely each group’s response rate has been estimated. The group sizes vary, from 8 participants in the HCV/HBV coinfection group to 50 participants in the treatment-experienced genotype 3 group. A percentage based on a small group will generally be less informative about the population value than the same percentage based on a much larger group, although the exact uncertainty depends on the observed outcome pattern and the interval method.

Intervals are available for some of the recalculated risk differences, but they are unadjusted and compare each listed group with the genotype 1 retreatment reference. Some intervals include zero, meaning that the simple calculation is compatible with no difference under the method used. Other intervals exclude zero. This alone does not settle whether the contrast is reliable or meaningful: group comparability, multiple comparisons, sample size, missing outcome handling, and the choice of calculation all matter.

For comparisons in which both observed percentages are 100.0%, the recalculated difference and displayed interval are all zero. Such a collapsed interval should not be interpreted as certainty about the underlying rates. It is tied to the observed boundary values and the simple recalculation. The registry record does not report a method for estimating uncertainty around each arm percentage or a sponsor analysis that could provide a different inferential framework. Overall, precision is difficult to judge from the arm percentages alone, especially in the smaller groups.

12. Multiplicity, Missing Data and Analysis Populations

The study reports a primary endpoint and multiple secondary outcomes, with results across several cohorts and treatment groups. This creates a multiplicity issue: when many outcomes or comparisons are considered, some results may appear notable by chance even if the underlying differences are absent. In general, prespecifying a primary comparison, controlling the family-wise error rate, using another adjustment, or defining a testing hierarchy can help clarify how multiple results should be interpreted. The registry record does not report such a plan, and the posted recalculated comparisons are unadjusted.

The absence of a reported multiplicity strategy does not show that no strategy was used; it means the strategy is not reported in the registry record. The record reports zero analyses and does not include sponsor-reported statistical comparisons for the primary outcome. The available contrasts are therefore not evidence of a documented confirmatory testing plan. They should be treated as exploratory, unadjusted calculations alongside the arm-level results.

The primary analysis population is defined as randomized participants who received at least 1 dose of study drug. This is the population description available for SVR12. The registry record does not report how missing post-treatment HCV RNA values were handled, whether participants lost to follow-up were counted as having no response, whether imputation was used, or whether sensitivity analyses evaluated alternative assumptions. It also does not report the number of missing primary endpoint observations within each group. These details matter because a percentage can change depending on how missing outcomes are classified or excluded.

The record does not report a sample-size justification, interim analysis plan, or complete statistical analysis plan. Without those details, it is not possible to assess the planned precision, the intended role of each cohort comparison, or whether the posted contrasts match prespecified analyses. These are documentation limitations; they do not establish that the study was conducted improperly. They do limit the strength of conclusions that can be drawn from the posted unadjusted results.

13. 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: hepatic cirrhosis (5.0%), lower respiratory tract infection (5.0%), hepatocellular carcinoma (5.0%), squamous cell carcinoma of the tongue (5.0%), encephalopathy (5.0%).

The safety results report serious adverse events and other adverse events by group. Serious adverse events were recorded in some groups and not in others; the reported counts range from zero to 4 across the listed groups. Other adverse events were reported in each group, with counts ranging from 6 to 43. These are counts, not percentages, and they should be read with the group-specific numbers at risk shown in the registry results. No percentages should be inferred from these counts without a defined denominator and calculation.

The serious-event terms listed as most frequent each have a reported value of 5.0%: hepatic cirrhosis, lower respiratory tract infection, hepatocellular carcinoma, squamous cell carcinoma of the tongue, encephalopathy, and acute kidney injury. The registry record does not supply further detail about event timing, severity grading, relationship to treatment, or whether events overlapped within participants. Death counts are not reported in the registry record.

In general, adverse-event counts describe what was recorded during a study; they do not by themselves show whether an event was caused by a regimen. The groups also differ in size and clinical characteristics, so counts across groups are not direct measures of comparative safety. The open-label design and the absence of detailed event-level context further limit causal interpretation. These figures should be read as descriptive safety reporting, not as proof of safety or harm.

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

The posted results describe SVR12 percentages in several groups of participants with chronic HCV infection who received different sofosbuvir-containing regimens. They show that the observed percentages were not identical across all groups. That pattern is useful for understanding the range of outcomes recorded in this study and for seeing how results varied across genotypes, treatment histories, liver conditions, and regimens represented in the cohorts.

The results do not establish that one regimen caused a higher or lower SVR12 rate than another across all populations. The arms differ in eligibility and clinical characteristics, and the simple recalculated comparisons are unadjusted. Although randomized allocation is reported for the trial, the registry record does not establish that every cross-cohort contrast represents a direct randomized comparison among otherwise comparable participants. The posted p-values therefore should not be treated as definitive evidence of superiority or equivalence.

The percentages also do not show the exact response rate that would occur in a future population. Individual arm confidence intervals are not reported, some groups are small, and the record does not explain how missing endpoint data were handled. A result of 100.0% in an observed group does not mean that every future participant would meet the endpoint or that uncertainty is absent.

SVR12 is a virologic endpoint at a defined post-treatment time. It does not describe all health outcomes, all potential adverse effects, or longer-term outcomes beyond the follow-up reported. The safety counts are descriptive and do not establish that a regimen caused an event. The registry record also lacks a reported multiplicity plan, sample-size justification, and sponsor statistical analyses for the posted comparisons. The most defensible reading is therefore descriptive and cohort-specific: the results show what was recorded in these groups, with important limits on comparative and causal interpretation.

15. Why This Trial Matters Statistically

This study is statistically notable for the breadth of its clinical groups and regimens within one Phase 2 record. It includes genotype 1, 2, 3, and 6 HCV, retreatment groups, treatment-naive groups, treatment-experienced groups, participants with cirrhosis or liver fibrosis, and participants with HBV coinfection. That variety allows the registry to present outcomes across settings that are not represented by one uniform population. It also makes careful comparison especially important: differences in observed percentages can reflect differences between groups as well as differences between regimens.

The study illustrates why a randomized label alone does not guarantee that every pair of posted arm percentages is a clean head-to-head treatment contrast. The allocation is reported as randomized, but the group descriptions vary considerably. The recalculated comparisons use one cohort as a reference, and the registry record does not report sponsor analyses that establish the intended inferential role of those contrasts. Distinguishing arm-level description from causal inference is central to interpreting multi-cohort trials.

It also highlights the importance of precision and reporting. Some groups are small, individual arm confidence intervals are not reported, and the record does not report missing-data methods, a sample-size justification, or a multiplicity plan. Unadjusted comparisons across multiple groups can be informative as exploratory summaries, but their evidential weight differs from a prespecified analysis with a stated statistical plan.

For biostatisticians and clinical researchers, the record is a useful example of how population definition, endpoint timing, comparator choice, and reporting detail shape interpretation. The percentages are meaningful as observations within the described groups; their broader meaning depends on design features and analysis details that are not reported in the registry record.

16. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The main trial-specific limitation is the heterogeneity of the cohorts. The groups differ by genotype, prior treatment response, treatment-naive or treatment-experienced status, fibrosis or cirrhosis, HBV coinfection, regimen, and duration. This makes broad comparisons across groups difficult to interpret as treatment effects. The first genotype 1 retreatment group serves as the reference for the posted recalculations, but it is not described as a common matched comparator for each clinical population.

The registry reports randomized allocation overall, but does not provide enough detail to determine how randomization operated across the cohorts or whether each listed contrast reflects randomized assignment between comparable groups. Masking was not used. The registry record does not report the randomization procedure, allocation concealment, or a sponsor analysis for the posted comparisons.

The primary endpoint is clearly defined, but arm-level confidence intervals are not reported. Group sizes vary, and several groups have few participants. The record does not report a sample-size justification, the handling of missing SVR12 outcomes, the number of missing outcome measurements, or sensitivity analyses. It also does not report a statistical analysis plan, multiplicity procedure, or interim analysis details. These omissions make it harder to assess precision, prespecification, and robustness.

Finally, the safety information is limited to group-level counts and selected serious-event terms. Death counts are not reported in the registry record, nor are event timing, treatment relationship, or detailed event-level descriptions. These limitations restrict comparative safety interpretation. They do not negate the observed results, but they define what can and cannot be concluded from the registry record.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Efficacy and Safety of Sofosbuvir Containing Regimens for the Treatment of Chronic HCV Infection in Participants With Chronic Genotype 1, 2, 3, or 6 HCV Infection — NCT01826981.
• Registry record last updated 2018-11-16; status last verified 2016-09.
• Results first posted 2016-09-16.
• 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.

20. Record Summary

This completed Phase 2, multicenter, randomized, open-label, parallel-group study assessed sofosbuvir-containing regimens for chronic HCV infection. Total enrollment was 359. The study included cohorts with genotype 1, 2, 3, or 6 and varied by treatment history, liver status, and HBV coinfection. Regimens and treatment durations differed across groups.

The primary endpoint was SVR12: HCV RNA below the lower limit of quantification 12 weeks after treatment discontinuation. The analysis population was randomized participants who received at least 1 dose of study drug. Posted arm percentages varied across groups. Recalculated comparisons use a genotype 1 retreatment group as reference and are unadjusted; the registry reports no sponsor analyses for them.

Important details, including missing-data handling, multiplicity procedures, sample-size justification, and a complete statistical analysis plan, are not reported in the registry record. The findings are best read as descriptive results within the specified cohorts, with limited basis for causal comparisons across groups.