Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients (NCT01054729), a randomized phase 2 study. The primary outcome is Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period.

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, double-blind, placebo-controlled, dose-ranging study. The registry describes a multicenter, parallel-group design and lists four groups: sofosbuvir 100 mg with PEG+RBV, sofosbuvir 200 mg with PEG+RBV, sofosbuvir 400 mg with PEG+RBV, and placebo with PEG+RBV. Enrollment was 64. Randomization was stratified by IL28B status, recorded as CC or CT/TT.

The active study drug or its matching placebo was taken once daily for 28 days, from baseline to Day 28. Participants in all groups also started PEG+RBV at baseline and continued it through Week 48. The registry describes additional evaluation for sustained virologic response for 24 weeks after completion of study treatment. These details place the primary safety observation window in the first four weeks, during the sofosbuvir or matching-placebo exposure, rather than across the full PEG+RBV course.

Blinding was supported by matching placebo tablets: participants receiving 100 mg active sofosbuvir took three placebo tablets, and those receiving 200 mg took two. The 400 mg group took four active tablets, while the placebo group took four matching placebo tablets. The registry describes the study as double-blind; it does not identify which specific personnel were masked or give details about how masking was maintained beyond the matching tablets.

The registry marks the trial completed and gives a start of 2010-01 and primary completion of 2010-04. It lists safety, tolerability, pharmacokinetics, and pharmacodynamics among the study aims. Beyond the randomized dose groups and the listed stratification, further details of the randomization procedure, allocation concealment, site count, or protocol amendments 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: 143 participants were screened and 64 were randomized; 63 participants were treated, and comprise the Safety Analysis Set.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set: participants 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: Participants who were randomized and treated were analyzed for Baseline Characteristics

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period, measured over Baseline to Week 4.

The primary endpoint was the percentage of participants who experienced adverse events during the sofosbuvir treatment period, from baseline to Week 4. A participant was counted once if they had a qualifying event. This participant-level rule means the endpoint concerns whether a person experienced at least one qualifying event in the specified period, rather than how many separate event episodes that person had.

Adverse-event outcomes are used to describe the safety experience observed during a defined exposure window. In this trial, the Week 4 endpoint aligns with the 28-day course of sofosbuvir or matching placebo. That timing is useful for keeping the primary safety summary tied to the randomized study-drug period, even though PEG+RBV continued for much longer.

The registry lists the endpoint as a percentage but posts group-level counts for serious and other adverse events, with the number at risk in each group. It does not give a separate overall percentage for the primary endpoint, define in the posted description the exact qualifying-event rule beyond counting a participant once, or provide an inferential analysis of the primary endpoint. The available counts therefore describe the recorded safety experience, but do not by themselves establish whether event frequency differed between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a participant-level binary safety outcome: whether a participant experienced an adverse event during the specified treatment period. The summary counts show participants with events and the corresponding number at risk in each group. No inferential analysis is listed for the primary outcome. The explanations below describe general statistical concepts relevant to this type of endpoint; they do not imply that these methods were used in the trial.

What does a participant-level percentage represent?

For a binary endpoint, each participant is classified according to whether the event occurred during the defined window. The resulting proportion describes the fraction of the analyzed group with at least one qualifying event. This differs from an event count, which could count repeated episodes in one person more than once. The registry says a participant was counted once if they had a qualifying event, so the unit in this endpoint is the participant.

The posted safety summaries distinguish serious adverse events from other adverse events. They report counts at risk and counts affected for each group. Since a participant may have more than one event or event type, a participant-level count does not convey the number, duration, severity, or recurrence of all events. The record does not describe whether serious and other categories are mutually exclusive or how events were classified if more than one category applied.

Why use a randomized placebo group?

In general, random allocation is intended to make the assigned groups comparable, on average, with respect to measured and unmeasured baseline characteristics. A placebo group receiving the same background PEG+RBV can help distinguish the experience during the randomized study-drug period from the experience under the background regimen. Double blinding can reduce some differences in care or reporting associated with knowledge of assignment. These are general design principles; the registry record does not report a check of baseline balance or a quantitative assessment of the success of masking.

The described stratification by IL28B status means that this factor was considered in allocating participants. Stratification can help balance a prespecified characteristic across groups. The registry does not report the randomization method, block sizes, allocation concealment details, or whether the primary analysis accounted for the stratification factor. Those analysis details are not reported in the registry record.

What would an inferential comparison add?

A group comparison would quantify how compatible the observed difference is with chance variation under a statistical model. A confidence interval, in general, expresses uncertainty around an estimated effect and shows a range of values compatible with the data and the chosen method. A p-value, in general, summarizes how unusual the data or a more extreme result would be under a specified null hypothesis and assumptions. Neither type of inferential result is listed for the primary endpoint in the registry record, so no such interpretation can be made.

For binary outcomes, methods may compare proportions directly or model the event probability. Method choice depends on the design, the event frequency, the analysis population, and whether adjustment is needed. With small group counts, approximate methods can be unreliable, and exact or other small-sample methods may be considered in general. The registry does not report which method was planned or used, and no adjusted or unadjusted comparison is posted.

How should the safety population be understood?

The stated Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug. This is a defined analysis population rather than necessarily every person enrolled or randomized. In general, analyses based on participants who received treatment can describe events during actual study-drug exposure, but the results may differ from an analysis retaining everyone as randomized if some participants did not start treatment or were excluded. The record does not provide a participant flow, reasons for any exclusions, or counts randomized but not treated.

The number at risk listed for each group is the denominator associated with these adverse-event summaries. It is important to keep each group’s denominator attached to its counts and not treat the overall enrollment as the denominator for each group. The registry gives no additional account of missing safety assessments or incomplete adverse-event reporting. Whether missingness occurred, and how it was handled, are not reported in the registry record.

What do the planning illustrations mean?

General sample-size calculations estimate how many participants might be needed for a future study to detect an assumed effect under specified statistical assumptions. They do not show that a trial with a given sample size had a particular probability of detecting an effect after the fact. The planning assumptions described for the posted illustration include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of the observed effect. Such illustrations are planning exercises, not observed power and not evidence that the original trial was designed around those assumptions.

The registry does not report the original trial’s sample-size justification, target effect, power calculation, interim analyses, or stopping rules. It also does not provide the statistical analysis plan for this endpoint. These omissions matter because they prevent a reader from assessing whether the posted endpoint analysis followed prespecified methods or whether any multiplicity adjustment was planned.

Why are multiple outcomes relevant?

The study lists several secondary outcomes, including Week 4 HCV RNA change, rapid virologic response, later sustained virologic response, and pharmacokinetic measures. When many outcomes or comparisons are examined, the chance of at least one apparently unusual result can rise. In general, multiplicity methods may control that risk, or outcomes may be interpreted as exploratory. The registry record does not report an analysis plan for handling multiple outcomes, and the absence of posted analyses for the primary outcome means there is no basis to infer how the wider set of outcomes was handled.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety endpoint and multiple secondary outcomes, including viral response measures and pharmacokinetic measurements. It does not report a multiplicity strategy, such as a hierarchy among endpoints, an adjustment to significance thresholds, or a distinction between confirmatory and exploratory testing. In general, testing several outcomes can increase the chance of at least one nominally unusual result. Without a reported plan, the results of any multiple comparisons should not be treated as if they were protected by a specific error-control procedure.

No analysis is listed for the primary outcome, and no p-values, confidence intervals, or adjusted estimates are posted for the adverse-event summaries. The registry record does not report interim analyses, stopping rules, missing-data methods, or a detailed statistical analysis plan. It also does not state whether the primary endpoint was analyzed as randomized, only among treated participants, or under another analysis set beyond identifying the Safety Analysis Set as participants randomized and receiving at least 1 dose.

The stated safety population defines who was eligible for the reported summaries, but the record does not give a full participant flow or explain whether any enrolled or randomized participants were omitted. It does not describe missing safety observations, how incomplete follow-up was addressed, or whether participants were followed for adverse events after the study-drug period. Thus, the posted counts are interpretable as summaries for the stated population and timeframe, but completeness and sensitivity to missing information cannot be assessed. The original sample-size justification is also not reported in the registry record.

11. 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: abdominal pain (7.1%), anaemia (6.7%), pancreatitis acute (6.7%), depression (6.7%), peripheral ischaemia (6.2%).

The safety summaries give the number at risk and the number of participants with serious or other adverse events during the specified period. Serious-event counts were 1 among 16 in the 100 mg group, 0 among 18 in the 200 mg group, 3 among 15 in the 400 mg group, and 1 among 14 in the placebo group. The corresponding counts for other adverse events were 14, 18, 13, and 13. These are counts of participants, not counts of every event episode.

The registry also lists serious adverse-event terms and percentages: Abdominal pain, 7.1%; Anaemia, 6.7%; Pancreatitis acute, 6.7%; Depression, 6.7%; and Peripheral ischaemia, 6.2%. The posted summary does not assign these terms to particular randomized groups or specify the denominators for the percentages. They should not be used as treatment-group comparisons.

The record shows no deaths value for the groups; deaths are not reported in the registry record. A blank or unreported value is not evidence of zero deaths. The serious-event counts are descriptive and do not establish that one group had a higher or lower underlying risk. The registry does not provide confidence intervals, comparative tests, or details of adjudication for these summaries.

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

The posted result is a descriptive account of participants with adverse events during the baseline-to-Week 4 sofosbuvir treatment period. The counts are reported separately for the three sofosbuvir dose groups and the matching-placebo group, all receiving PEG+RBV. They allow a reader to see how many participants at risk were recorded with serious and other adverse events in each group. The registry also lists several serious adverse-event terms as percentages, without group assignment or denominator details in the posted summary.

The result does not establish that one dose caused more or fewer adverse events than another dose or placebo. There is no inferential comparison, confidence interval, or p-value reported for the primary endpoint. Differences between the observed counts can reflect chance variation, especially when group sizes are limited; the record does not quantify the uncertainty around any difference. The summaries also do not give event timing within the four-week window, recurrence, duration, or a complete breakdown of all event types.

The scope is limited to the stated safety population and treatment window. PEG+RBV continued through Week 48, but the primary endpoint covers only the sofosbuvir treatment period through Week 4. The registry describes later evaluation for virologic response, but that is distinct from the primary safety question. The adverse-event counts should not be interpreted as a full account of safety across the entire treatment and follow-up period.

The study’s randomized, double-blind, placebo-controlled design provides a framework for comparing groups, but design alone does not substitute for a reported analysis. The posted record lacks the analysis details and inferential results needed to assess comparative precision. These data are therefore useful as a record of observed counts, not as proof of equivalence, a dose-response relationship, or a treatment effect. They do not support medical advice or an individual treatment decision.

13. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition, analysis population, and observation window must accompany any safety count. The primary endpoint was framed as the percentage of participants with an adverse event during the sofosbuvir treatment period, and the registry states that each participant was counted once for a qualifying event. The posted group summaries distinguish serious and other adverse events and specify the number at risk. Those definitions help clarify what the counts represent, while also showing that a participant-level summary does not capture every episode or its clinical course.

The design also raises a common interpretation issue in combination therapy. The randomized groups differed in the assigned sofosbuvir dose or matching placebo, while PEG+RBV was part of all four regimens. The primary safety window coincided with the short study-drug course, whereas the background treatment continued to Week 48. Keeping that timing clear prevents readers from treating a four-week safety summary as a complete account of the longer regimen.

Statistically, randomized groups make comparative analysis possible, but the registry posts no primary-outcome analysis. Counts alone do not reveal the precision of group differences. This is especially important when there are few participants and relatively few serious events: descriptive patterns can look different even when uncertainty is substantial. No uncertainty interval or test is reported to distinguish a stable contrast from sampling variation.

The record further demonstrates the difference between trial design and the evidence available for interpretation. It describes randomization, masking, a placebo comparator, and stratification, but does not report the original sample-size rationale, detailed analysis plan, or multiplicity handling. Those missing details constrain assessment of prespecification and statistical strength. The key statistical lesson is that a well-described design and a set of event counts are not, by themselves, a complete comparative analysis.

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.

The registry record does not report a statistical comparison for the primary safety endpoint. Although the adverse-event counts and numbers at risk are posted by group, no confidence intervals, p-values, adjusted estimates, or analysis method accompany them. As a result, the precision of any between-group contrast cannot be evaluated from the record.

The reported primary endpoint is a percentage of participants with adverse events, but the posted safety summaries separate serious from other adverse events. The record does not explain whether these categories are mutually exclusive, provide a complete event-by-event listing by group, or clarify the relationship between those summaries and the overall primary endpoint. The serious adverse-event term percentages are not linked to a treatment group or denominator in the posted summary.

The analysis population is described as participants randomized and receiving at least 1 dose of study drug, but no participant flow or reasons for any exclusions are reported. Missing-data handling, completeness of safety follow-up, and details of adverse-event ascertainment are not reported in the registry record. Deaths are not reported by group; the record does not establish that there were none.

The short primary safety window ends at Week 4, even though PEG+RBV continued through Week 48 and additional evaluation followed treatment. The primary endpoint therefore does not summarize adverse events over the full treatment and follow-up course. Finally, the registry does not report the trial’s original sample-size justification, interim analyses, stopping rules, or a detailed plan for handling multiple outcomes. These omissions limit assessment of both the intended statistical design and the completeness of the posted results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients — NCT01054729.
• Registry record last updated 2014-04-17; status last verified 2014-03.
• Results first posted 2014-02-19.
• 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

NCT01054729 was a completed phase 2 randomized, double-blind, placebo-controlled dose-ranging trial in treatment-naïve participants with genotype 1 HCV infection. Enrollment was 64. Participants received sofosbuvir 100 mg, 200 mg, or 400 mg, or matching placebo, with PEG+RBV. The assigned sofosbuvir or placebo course lasted 28 days; PEG+RBV continued through Week 48.

The primary endpoint concerned participants experiencing adverse events from baseline to Week 4. The safety summaries list serious and other adverse-event counts by group, with the corresponding number at risk. No inferential analysis of the primary endpoint is listed. The record does not report confidence intervals, p-values, a detailed analysis plan, multiplicity handling, missing-data methods, or the original sample-size justification. The posted counts are descriptive and do not establish comparative safety differences.