Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection (NCT02349048), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12).

2. Clinical Question

The clinical question is whether the specified treatment regimens were followed by an undetectable or below-quantification HCV RNA result at the stated post-treatment assessment. The record defines this outcome using HCV RNA below the lower limit of quantification, 15 international unit per milliliter, or undetectable. It also lists outcomes covering response during treatment, SVR4 and SVR24, treatment failure, viral relapse, sequence findings among participants not achieving SVR, and SVR according to the presence or absence of an NS3 Q80K polymorphism at baseline.

The groups differ both in the liver-fibrosis descriptions and in treatment duration. Because the allocation is recorded as non-randomized, their outcomes should not be interpreted as a direct causal comparison of 6 weeks versus 8 weeks. The registry record does not report the primary outcome results, so the clinical question cannot be answered from the posted results described in this record.

3. Trial Design

This was a Phase 2, open-label, parallel-group study. The registry lists the allocation as non-randomized and masking as none. Its official title describes it as randomized, creating an inconsistency between the title and the allocation field. The registry record does not explain that discrepancy; the recorded allocation field indicates that the arms are not a randomized comparison.

The record lists total enrollment of 68. Arm A comprised participants with chronic HCV genotype 1 infection and early stages of liver fibrosis, treated once daily with simeprevir 150 mg, daclatasvir 60 mg and sofosbuvir 400 mg for 6 weeks. Arm B comprised participants with cirrhosis, treated with the same listed daily doses for 8 weeks. Thus, arm membership is linked to both the clinical description and the treatment duration. These groups are not interchangeable control groups.

The study status is completed. The registry lists the start as 2015-01 and primary completion as 2016-02. Janssen Research & Development, LLC is named as sponsor. The stated purpose was to evaluate efficacy, safety, tolerability and pharmacokinetics of the regimens in treatment-naive participants with early stages of liver fibrosis or cirrhosis.

A non-randomized design can describe outcomes in the enrolled groups, but it does not ensure that groups are comparable in all respects. Here, the fibrosis categories and durations differ by arm, so any contrast could reflect these distinctions as well as other differences between participants. The registry record does not report a separate control treatment, a random allocation procedure, or a protocol rationale for assigning the different durations to the described groups. The primary endpoint results 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Intent-to-treat (ITT) analysis set is defined as all enrolled participants who took at least 1 dose of Simeprevir (SMV), Sofosbuvir (SOF) or Daclatasvir (DCV).

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12), measured over 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B).

The primary endpoint was the percentage of participants with sustained virologic response 12 weeks after the end of study drug treatment, called SVR12. The registry defined response as HCV RNA below the lower limit of quantification, 15 international unit per milliliter, or undetectable at the specified assessment. The assessment was at week 18 for Arm A and week 20 for Arm B, reflecting the different treatment durations.

As a general statistical concept, a binary endpoint classifies each participant according to whether a defined event or criterion is met. A percentage expresses the frequency of participants meeting that definition in the analysis population. SVR12 is a post-treatment virologic endpoint: it asks whether the specified HCV RNA criterion was met after treatment had ended, rather than measuring a change during dosing. Its interpretation depends on the assay threshold, assessment timing and analysis population, all of which determine what counts as a response.

The record defines the primary analysis population as the intent-to-treat (ITT) analysis set: all enrolled participants who took at least 1 dose of simeprevir, sofosbuvir or daclatasvir. Although this definition is stated, the registry record does not report the number achieving SVR12 or the corresponding percentage for either arm. Without those results, the endpoint definition can be described, but the observed response cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information available in the registry record is limited. It identifies the primary endpoint as a percentage and defines the analysis population, but does not report the primary outcome estimates or an inferential analysis. The methods below distinguish general statistical principles from the information documented for this study.

What does a percentage endpoint represent?

As a general statistical concept, a percentage for a binary outcome is based on participants who meet a specified criterion relative to the analysis population. Here, the criterion was HCV RNA below the lower limit of quantification, 15 international unit per milliliter, or undetectable at the SVR12 assessment. The percentage depends on both the number meeting the criterion and the number evaluated under the stated analysis definition. The registry record gives the ITT population definition but does not report the primary endpoint counts or percentages.

A percentage is an estimate of an underlying response frequency, not a certainty about what would occur in every similar participant. Its precision is ordinarily conveyed by an uncertainty interval, such as a confidence interval. As a general explanation, a confidence interval describes a range of values reasonably compatible with the data and the statistical method used. A narrow interval indicates greater precision than a wide interval. No confidence interval for SVR12 is reported in the registry record, so its precision cannot be evaluated.

Why does the design affect interpretation?

The record identifies a parallel-group, open-label study, with no masking and non-randomized allocation. It also describes different fibrosis categories and different treatment durations across the arms. In a randomized comparison, allocation by chance is intended to balance measured and unmeasured characteristics on average; this record does not document such an allocation and explicitly flags the arms as not a like-for-like control comparison. Consequently, a contrast between arm outcomes would be descriptive rather than a clean estimate of the effect of duration alone.

Open-label means masking was absent, as the registry field states. In general, knowledge of treatment assignment can affect some aspects of care, reporting or assessment, depending on the outcome and procedures. The record does not report how any such potential influences were addressed. The primary endpoint is based on a laboratory-defined HCV RNA criterion, but no further details about assessment procedures or handling of measurements are reported in the registry record.

What analysis plan is documented?

The ITT analysis set is defined as all enrolled participants who took at least 1 dose of one of the listed study drugs. That definition identifies who was intended to contribute to the primary endpoint analysis. The registry record does not report how missing SVR12 assessments, treatment discontinuations, or other unavailable outcome data were handled. It also does not report the statistical test, model, adjustment variables, confidence-interval method, or a prespecified analysis plan for the primary endpoint.

The record lists secondary endpoints, but their presence does not establish how each was analyzed or whether any formal multiplicity adjustment was planned. Multiplicity is a general issue that arises when several outcomes, time points or subgroup comparisons are examined: the chance of at least one apparently notable result can increase when many tests are considered. Whether and how that issue was addressed is not reported in the registry record.

Why is over-dispersion not relevant to the listed primary measure?

Over-dispersion is a general concern for count outcomes when variability exceeds what a simple probability model expects. The primary endpoint is a percentage of participants meeting a binary response definition, not a count rate or time-to-event outcome. The registry record does not report a statistical model for the endpoint, so no claim can be made about whether a particular variance adjustment was used. The concept should not be mistaken for a documented feature of this analysis.

How should planning calculations be read?

Sample-size calculations are planning illustrations, not observed results. General planning calculations may show how a hypothetical effect and design assumptions relate to the number of participants needed for a chosen power and significance level. Such illustrations are not the trial’s observed power, do not show that an effect occurred, and do not replace the trial’s own design justification. The registry record does not report a sample-size justification or the assumptions used by the trial team.

The record’s planning description states that its illustration uses a two-sided significance level of 0.05, equal allocation between arms, a normal approximation and a target effect expressed as a fraction of the observed effect. It also distinguishes participants per arm for most outcomes from total events for time-to-event calculations. These are description-level assumptions for an illustration, not evidence that the study used those assumptions prospectively. The record does not report the trial’s own sample-size rationale. In particular, the overall enrollment of 68 is not, by itself, evidence of the precision achieved for SVR12 or of a prospective power target.

What can be concluded from the available methods detail?

The endpoint threshold, assessment timing and ITT population definition are documented. The primary endpoint results and their uncertainty are not. Important details about missing data, multiplicity, analysis procedures and the sample-size justification are also not reported in the registry record. Statistical interpretation must therefore remain descriptive: the study’s setup can be explained, but the efficacy estimate and its precision cannot be reconstructed from 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("Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks", "Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks")
n      <- c(59, 9)
events <- c(51, 9)
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  Arm A: Simeprevir/Daclatasvir/Sofosbuvir - 6 Weeks  59  51  86.4  75.0  94.0  75.5  93.0  75.4  92.9
ARM  Arm B: Simeprevir/Daclatasvir/Sofosbuvir - 8 Weeks  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcomes. These include virologic response during treatment, SVR4 and SVR24, on-treatment failure, viral relapse, late viral relapse, viral sequence findings among participants not achieving SVR, and SVR by baseline NS3 Q80K polymorphism status. Considering multiple outcomes can raise a multiplicity issue. As a general statistical matter, the more comparisons assessed, the greater the opportunity for chance findings unless analyses are planned and interpreted with that context. Whether multiplicity was controlled, and by what method, is not reported in the registry record.

The record defines the ITT analysis set as all enrolled participants who took at least 1 dose of simeprevir, sofosbuvir or daclatasvir. It does not explain how participants with missing SVR12 measurements, incomplete follow-up or other unavailable outcome data were handled. Missing-data handling matters because the observed percentage can depend on whether such participants are excluded, counted as nonresponders, or handled through another method. No such approach should be assumed for this study.

The registry record also does not report a detailed statistical analysis plan, model, confidence-interval method or sample-size justification. It lists 68 participants overall, but that enrollment figure does not establish the intended power or precision. The recorded allocation is non-randomized; the groups differ in fibrosis description and treatment duration, so comparisons are not equivalent to a randomized control contrast. These design features should inform interpretation alongside the absence of reported primary results.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain (1.7%), headache (1.7%).

The serious adverse-event figures are descriptive counts. The record lists 59 participants at risk in Arm A, with 1 affected by a serious adverse event, and 9 at risk in Arm B, with 0 affected by a serious adverse event. The registry lists Chest Pain and Headache among the top serious terms, each at 1.7%. It does not assign those listed terms to a specific arm in the adverse-event information presented.

The record also lists 39 participants with other adverse events in Arm A and 4 in Arm B, among the same respective at-risk groups. These figures are not a like-for-like safety comparison: the arms differ in size, fibrosis description and treatment duration, and allocation is recorded as non-randomized. Counts alone do not establish that treatment duration caused any difference.

Deaths are not reported in the registry record. The serious-event counts and listed terms do not describe severity beyond the registry’s serious classification, event timing, duration, outcome or relationship to study treatment. Nor do they provide a complete account of individual clinical circumstances. They should be read as the adverse-event information recorded, not as a standalone assessment of comparative safety.

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

The trial’s primary question concerns the proportion of participants meeting a defined HCV RNA criterion 12 weeks after completing study drug treatment. The registry record specifies the threshold and the assessment timing for each arm, and identifies the population intended for the primary analysis. These design details clarify what SVR12 means in this study.

The record does not report how many participants achieved SVR12 or the percentage in either arm. It therefore does not establish the observed response frequency, its precision, or whether the result differed between the groups. It also does not report the listed secondary endpoint results. Describing an endpoint and evaluating it are distinct: a definition alone is not an outcome finding.

The study is not a like-for-like comparison of treatment durations. Arm A was described as participants with early stages of liver fibrosis receiving 6 weeks of treatment; Arm B was described as participants with cirrhosis receiving 8 weeks. The allocation field is non-randomized. Any contrast between these arms would combine differences in group description and treatment duration, among other possible differences, rather than isolate the effect of duration.

The safety counts provide a limited descriptive record: 1 serious adverse event in Arm A and 0 in Arm B, with other adverse events recorded for 39 participants in Arm A and 4 in Arm B. The groups differ in size, and the record does not provide enough detail to interpret these counts as evidence of a causal safety difference. Deaths are not reported in the registry record.

The appropriate reading is therefore narrow. The registry documents a Phase 2, open-label, non-randomized study and defines its endpoints, but does not post the primary efficacy results. No conclusion about the magnitude, direction or precision of an SVR12 effect can be drawn from the registry record. The absence of a posted result should not be converted into a positive or negative treatment conclusion.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and design details must be read together. SVR12 is defined by a specific HCV RNA criterion at a specified interval after treatment ends. The registry also gives arm-specific study weeks for that assessment, making clear that the endpoint timing is aligned to treatment completion even though the study-week number differs between arms.

At the same time, a well-defined outcome does not resolve limitations in the comparison. The arms represent different fibrosis descriptions and different treatment durations, and allocation is listed as non-randomized. A difference between outcomes could not be attributed to duration alone using the design description in the registry. This is an important distinction between reporting outcomes by group and estimating a causal treatment contrast.

The record also shows why the existence of multiple endpoints is not equivalent to the availability of results. It lists a broad set of virologic secondary outcomes, yet does not report the primary endpoint result or the secondary outcome findings. In the absence of estimates and uncertainty intervals, readers cannot evaluate either the magnitude or precision of the outcome.

Finally, the safety information is also bounded by what is recorded: adverse-event counts and serious-event terms are listed, while deaths are not reported. These figures offer descriptive information, but do not support an adjusted comparative safety assessment. The trial is statistically informative as an example of how population, allocation, treatment duration, endpoint timing and result reporting shape interpretation. Its posted record permits a careful account of design and outcome definitions, not a quantitative conclusion about efficacy.

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 most important limitation for interpreting efficacy is that the registry record does not report the primary SVR12 result. No response percentage, uncertainty interval or inferential comparison is available in the record. Results for the listed secondary outcomes are also not reported there.

The arms are structurally different. Arm A is described as participants with early stages of liver fibrosis receiving 6 weeks of treatment, while Arm B is described as participants with cirrhosis receiving 8 weeks. Allocation is recorded as non-randomized, and the registry explicitly cautions that the arms are not a like-for-like control comparison. A direct contrast would not isolate the role of treatment duration.

There is an inconsistency in the registry record: the official title calls the study randomized, while the allocation field says non-randomized. The record does not reconcile these descriptions. The allocation field and the stated caution about the arms are therefore important context for reading the design.

The record defines the ITT population but does not report how missing outcome assessments or discontinuations were handled. It does not report a detailed statistical analysis plan, multiplicity approach, confidence-interval method or sample-size justification. These omissions limit assessment of how the outcomes would have been estimated and how robustly they could be interpreted.

The safety information is limited to participant counts, selected serious-event terms and percentages. Deaths are not reported in the registry record, and details such as event timing, duration and relationship to treatment are not included in the information described. The unequal arm sizes and different group descriptions further constrain any comparative reading of safety counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection — NCT02349048.
• Registry record last updated 2017-03-01; status last verified 2017-01.
• Results first posted 2017-03-01.
• 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

NCT02349048 is a completed Phase 2, open-label, parallel-group study sponsored by Janssen Research & Development, LLC. The record lists 68 enrolled participants with treatment-naive chronic HCV genotype 1 infection. Arm A is described as participants with early stages of liver fibrosis receiving simeprevir 150 mg, daclatasvir 60 mg and sofosbuvir 400 mg once daily for 6 weeks. Arm B is described as participants with cirrhosis receiving the same doses for 8 weeks.

The primary endpoint is SVR12, defined using HCV RNA below the lower limit of quantification, 15 international unit per milliliter, or undetectable. Its results are not reported in the registry record. Allocation is listed as non-randomized, and the record cautions that the arms are not a like-for-like control comparison. Serious adverse-event counts are 1 in Arm A and 0 in Arm B; deaths are not reported in the registry record.