Open-Label, Bridging Study of Telaprevir in Treatment-Naïve and Treatment-Experienced Russian Patients With Genotype 1 Chronic Hepatitis C: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label, Bridging Study of Telaprevir in Treatment-Naïve and Treatment-Experienced Russian Patients With Genotype 1 Chronic Hepatitis C (NCT01498068), a non-randomized phase 3 study. The primary outcome is Number of Participants With Extended Rapid Virologic Response (eRVR).

2. Clinical Question

The study’s stated purpose was to determine the effectiveness, safety, and tolerability of the combination regimen in Russian participants with genotype 1 chronic hepatitis C. The clinical question is descriptive: it concerns outcomes among participants receiving the regimen, not the difference between the regimen and a randomized control treatment. The treatment-naïve and treatment-experienced groups may differ in relevant ways, so their results should not be treated as if participants had been randomly assigned between equivalent groups.

The primary endpoint focuses on a specified early virologic response. It records whether a participant met the RNA threshold at both scheduled assessment times, rather than measuring a change in symptoms or comparing treatment strategies. The registry record does not report the observed number or proportion who met this definition. It therefore does not establish the frequency of eRVR in the study population, nor does the primary endpoint information alone answer a comparative treatment question.

3. Trial Design

This was a Phase 3, open-label, non-randomized, single-group study with enrollment of 36. The registry lists the study as completed. Its recorded start was 2012-01 and its primary completion was 2012-04. Janssen-Cilag International NV is listed as the sponsor.

The treatment-naïve and treatment-experienced groups received the same named drug combination: telaprevir, pegylated interferon-alfa-2a, and ribavirin. The treatment-naïve regimen description specifies telaprevir 750 mg every 8 hours for 12 weeks, pegylated interferon-alfa-2a 180 microgram weekly, and ribavirin 1000 - 1200 mg daily, dependent on weight, for 24 or 48 weeks. The treatment-experienced description gives the same regimen and duration information. The registry text says total treatment duration is based on prior treatment status and liver disease, but the available description is truncated after that point; further details are not reported in the registry record.

Non-randomized allocation means that the registry does not describe random assignment to treatment groups. The treatment-history groups are not a like-for-like control comparison: treatment history defines the groups, and the record does not report a separate untreated or alternative-treatment control. Open-label status means masking is listed as none. The record does not report whether outcome assessment involved any additional procedures to reduce the influence of this design on measurement or reporting.

The single-group designation and the presence of treatment-history categories should be read together: the registry describes a treated cohort whose participants are classified by prior treatment status, not a randomized trial of the combination against another regimen. No protocol-level detail about recruitment, eligibility criteria beyond the stated population, or the rationale for the design is 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: Of the 39 participants screened, 36 participants (16 treatment-naïve/ 20 treatment-experienced) were enrolled and treated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis (FA) population: All participants who received at least one dose of the study medication.

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 Number of Participants With Extended Rapid Virologic Response (eRVR), measured over Week 4 and Week 12.

The primary endpoint is the number of participants with extended rapid virologic response. The registry defines eRVR as HCV RNA less than 25 IU/mL, with target not detected, at both Week 4 and Week 12 of treatment. This is a joint criterion: a participant must meet the stated RNA condition at each of the specified assessments to qualify as having eRVR.

As a count endpoint, it describes how many participants in the analysis population met the definition. It does not itself provide the proportion unless a denominator is also used, and it does not measure the size of an RNA change. The endpoint’s specified population is the full analysis population, comprising participants who received at least one dose of study medication. The registry record does not report the observed count or denominator for the primary outcome, so the actual frequency of eRVR cannot be read from the endpoint definition alone.

In general, an early virologic endpoint can provide a standardized way to describe response at prespecified treatment assessments. Requiring the RNA threshold at both visits makes the endpoint dependent on results at both time points; a participant who does not meet the criterion at either assessment does not satisfy the stated definition. That feature makes the endpoint distinct from a single-visit result or a continuous measure of RNA change. The registry record does not report the rationale for selecting this endpoint, how missing measurements were classified, or whether eRVR was used to guide later treatment duration.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are only partly described in the registry record. The primary endpoint is a participant count, and the record specifies the full analysis population as all participants who received at least one dose of study medication. It does not report the statistical analysis used for the primary endpoint, an uncertainty interval, or an analysis population count. The number of registered analyses is zero. That registry field does not establish that no analyses were performed; it means the record does not list registered analysis entries.

What does the count represent?

For a binary endpoint such as eRVR, participants are classified according to whether they meet the endpoint definition. The reported count would be the number meeting the HCV RNA criterion at both Week 4 and Week 12. In general, a proportion can be formed by relating that count to the relevant analysis denominator. The registry record does not report the observed primary count or denominator, so neither an event proportion nor its precision can be described from the available endpoint information.

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the method used. It does not guarantee that the true value lies within the interval, and it does not account automatically for every source of bias. An interval around a response proportion would describe sampling uncertainty for the analyzed participants, but it would not correct the limitations of a non-randomized design, open-label assessment, incomplete outcome data, or differences between treatment-history groups. No primary endpoint confidence interval is reported in the registry record.

Why does the design matter for inference?

Randomization is a method for balancing, on average, measured and unmeasured baseline factors between assigned groups. This study is listed as non-randomized and single-group, so it does not offer that design basis for a causal comparison. The treatment-naïve and treatment-experienced groups are defined by prior treatment status; their outcomes could reflect differences in participant history as well as response to the regimen. A contrast between these groups would not have the same interpretation as a randomized treatment contrast.

In general, an uncontrolled study can describe what happened among those enrolled and treated. It cannot determine what would have happened to the same participants under an alternative treatment using the study’s observed outcomes alone. A historical or external comparison would require its own data and assumptions; such a comparison is not described in the registry record. The open-label designation also means masking is listed as none. The registry record does not report blinded outcome review or other methods used to mitigate potential influence of treatment awareness.

What can the sample-size planning illustrate?

The study’s sample-size assumptions are described as a planning illustration computed from the observed effect, rather than as the trial’s own design. The stated framework uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, the planning convention is participants per arm for 80% power or 90% power. The registry record does not report the trial’s own sample-size justification or design assumptions.

In general, a sample-size calculation asks how much information a planned study would need to detect an assumed effect under specified statistical conditions. Its output depends on the chosen effect size, variability or event frequency, significance level, allocation, and analysis method. A planning calculation is not a description of the number of participants who experienced an outcome. Nor does it establish the power achieved by a completed study. In particular, a calculation based on an observed effect is a retrospective planning illustration, not observed power and not evidence that the estimate is precise or reproducible. The record does not state an interim-analysis plan or provide the values of any sample-size illustrations.

How should event counts and uncertainty be viewed?

In general, event counts are easier to interpret when accompanied by clear denominators, definitions, and uncertainty estimates. A small count can be compatible with a range of underlying event rates, and the degree of uncertainty depends on the amount of information and the analysis assumptions. The serious adverse event figures are counts by treatment-history group, not a randomized comparison. The record does not report inferential tests or confidence intervals for these safety counts.

Over-dispersion is a general concern when observed variation is greater than expected under a simple probability model, for example because participants’ risks differ or observations are correlated. In that circumstance, a model that assumes less variation may understate uncertainty. The registry record does not report a model for the primary outcome or evidence that over-dispersion was assessed; this concept therefore cannot be tied to a specific analysis in this study. More broadly, the absence of a reported statistical plan means the record does not establish which model, adjustment variables, missing-data rules, or multiplicity procedures were used.

These method distinctions matter because an endpoint’s definition, an observed estimate, and a causal interpretation are separate things. The definition tells the reader what qualifies as an event. An estimate would quantify observed experience in a specified population, while an uncertainty measure would describe its precision under a chosen method. A causal treatment comparison requires an appropriate design and analysis. The registry record supplies the definition and design classification, but does not report the primary outcome estimate, its uncertainty, or the analytical details needed to go further.

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("Treatment-naïve", "Treatment-experienced")
n      <- c(16, 20)
events <- c(13, 18)
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  Treatment-naïve  16  13  81.2  54.4  96.0  57.0  93.4  56.6  93.2
ARM  Treatment-experienced  20  18  90.0  68.3  98.8  69.9  97.2  69.6  97.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes, including median change in log10 HCV RNA, rapid virologic response at Week 4, RNA below the stated threshold at scheduled assessments, virologic failure, and treatment-outcome categories. Multiple outcomes create a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase if no adjustment or prespecified interpretation strategy is used. The registry record does not report a multiplicity-adjustment method, a testing hierarchy, or which secondary outcomes were intended to support confirmatory conclusions.

The record does not report how missing endpoint measurements were handled. This matters for eRVR because the definition requires RNA results at both Week 4 and Week 12. In general, a missing assessment may be treated as not meeting the endpoint, excluded from a particular calculation, or handled through another prespecified approach; these choices can change the estimate and its denominator. None of those rules is stated in the registry record. The full analysis population is defined as participants who received at least one dose, but the record does not give the observed size of that population or say how it relates to missing outcome data.

The registry lists zero analyses. This does not reveal whether analyses took place outside the registry record, and it should not be interpreted as evidence that outcomes were not analyzed. The statistical analysis plan, interim-analysis procedures, and any prespecified approaches to subgroup or sensitivity analyses are not reported in the registry record. As a result, the extent to which the listed outcomes were analyzed according to prespecified methods cannot be assessed.

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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events separately for the treatment-naïve and treatment-experienced groups. The serious-event count is zero in each group, with 16 and 20 participants at risk, respectively. These figures describe the entries recorded for the study; they do not establish that serious events were impossible, or that the regimen is free of serious risk. The registry does not report event-specific serious adverse event terms.

For other adverse events, the record lists 16 affected participants among 16 at risk in the treatment-naïve group and 19 affected participants among 20 at risk in the treatment-experienced group. The record does not provide event terms or severity details for these figures in the registry record for interpretation. They should not be confused with the serious adverse event counts, which are separately recorded.

These are descriptive counts in a non-randomized, open-label study. They do not establish whether an event was caused by study medication, and they do not support a causal safety comparison between the treatment-history groups. The deaths field is not reported in the registry record. Information about event timing, duration, management, discontinuations, and follow-up is also not reported in the registry record.

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

The record establishes that a Phase 3 study evaluated telaprevir in combination with pegylated interferon-alfa-2a and ribavirin among Russian participants with genotype 1 chronic hepatitis C. It specifies treatment-naïve and treatment-experienced groups and defines the primary endpoint as eRVR: HCV RNA less than 25 IU/mL, target not detected, at Week 4 and Week 12. It also records selected adverse-event counts.

What the record does not report is the observed primary endpoint result. The count of participants with eRVR, the corresponding analysis denominator, and a measure of uncertainty are not present in the registry record. The endpoint definition therefore cannot be used to infer how many participants achieved it or how precisely any response rate was estimated. The stated purpose of determining effectiveness and tolerability should not be mistaken for a result.

Even if a response estimate were available, its interpretation would be bounded by the design. This was a single-group, non-randomized and open-label study, not a randomized comparison against another regimen. Outcomes among enrolled participants could be described, but they would not by themselves show what would have occurred under an alternative treatment. The treatment-history categories are not interchangeable control arms because participants were classified by prior treatment status.

The safety figures similarly describe registered counts rather than comparative risk or causality. Zero recorded serious adverse events in the groups does not prove absence of risk, while the other adverse-event counts do not identify the events or establish their relation to treatment. Missing data, analysis methods, and additional safety details are not reported in the registry record.

In general, statistical evidence is strongest when the outcome definition, denominator, estimate, uncertainty, analysis population, and study design can all be considered together. Here, the design and endpoint definition are stated, but the primary outcome estimate and key analysis details are not. The appropriate interpretation is therefore limited: the registry records what the study set out to evaluate and selected safety counts, but does not provide enough primary outcome information to characterize observed eRVR or make a treatment-effect comparison.

14. Why This Trial Matters Statistically

This study is statistically notable because it demonstrates the distinction between a defined endpoint and a reported result. The registry gives a precise operational definition of eRVR, including its RNA threshold and both assessment times, but does not report the observed number meeting that definition. Readers therefore cannot move from knowing what counted as a response to knowing how often the response occurred.

The design classification is equally important. A non-randomized, single-group study can contribute descriptive information about participants receiving a regimen, but it does not offer a randomized control contrast. The treatment-naïve and treatment-experienced categories describe prior treatment status, not random allocation. Statistical comparisons between those categories would be vulnerable to differences associated with their histories and should not be interpreted as a randomized estimate of treatment effect.

The registry also lists a sample-size planning framework based on an observed effect. Such illustrations can help explain what a future study might plan to detect under specified assumptions, but they are not the completed trial’s own design justification and are not observed power. Keeping this distinction clear prevents planning calculations from being mistaken for evidence about the precision or reliability of the trial result.

Finally, the safety counts show why denominators and event definitions matter. Serious adverse events and other adverse events are recorded separately, and their counts are descriptive. Without detail on the events, missing data, or analytic methods, those counts cannot support more elaborate safety comparisons. For clinical researchers, the record’s main statistical lesson is the need to assess endpoint results, denominators, uncertainty, analysis rules, and design together rather than treating an endpoint label or count as a complete treatment-effect conclusion.

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 is that the registry record does not report the observed primary outcome. The eRVR definition is available, but its count, analysis denominator, and uncertainty are not. This prevents assessment of the primary endpoint’s frequency and precision using the information in the record.

The non-randomized, single-group design provides no randomized comparator. The treatment-naïve and treatment-experienced groups differ by prior treatment status and cannot be regarded as equivalent control groups. As a result, the design does not support a causal comparison of the regimen with an alternative treatment. Open-label status and the absence of masking are recorded, but procedures for limiting assessment or reporting bias are not reported in the registry record.

Further interpretive details are missing. The registry does not report the sample-size justification for the trial, the statistical analysis plan, missing-data rules, multiplicity procedures, interim-analysis methods, or the handling of protocol deviations. It also does not provide detailed event terms for the other adverse-event counts, or a deaths figure. The treatment-duration description mentions prior treatment status and liver disease as factors, but the registry text is truncated before additional detail is given.

These limitations apply to interpretation of the registry record; they do not establish that the omitted methods or outcomes were absent from other study materials. They mean that conclusions relying on those details cannot be verified from the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-Label, Bridging Study of Telaprevir in Treatment-Naïve and Treatment-Experienced Russian Patients With Genotype 1 Chronic Hepatitis C — NCT01498068.
• Registry record last updated 2015-01-30; status last verified 2015-01.
• Results first posted 2013-12-30.
• 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

NCT01498068 is a completed Phase 3, open-label, non-randomized, single-group study of telaprevir with pegylated interferon-alfa-2a and ribavirin in Russian participants with genotype 1 chronic hepatitis C. Enrollment was 36. The primary endpoint was the number of participants with eRVR, defined as HCV RNA less than 25 IU/mL, target not detected, at Week 4 and Week 12, in the full analysis population of participants who received at least one dose.

The record lists treatment-naïve and treatment-experienced groups and reports selected adverse-event counts, but does not report the observed primary endpoint result or its uncertainty. It offers no randomized control comparison. The record’s design, endpoint definition, and safety counts support a limited descriptive account, not a comparative estimate of treatment effect.