This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Subjects With Chronic Genotype 4 Hepatitis C Virus Infection (NCT02250807), a na phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02250807 |
| Phase | Phase 3 |
| Condition | Chronic Hepatitis C, Genotype 4 Chronic Hepatitis C |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 40 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Janssen R&D Ireland |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled treatment-naive or treatment-experienced subjects with chronic genotype 4 hepatitis C virus infection. The registry record lists enrollment of 40. Its stated intent-to-treat population included randomized participants who received at least 1 dose of study medication; how that definition applies to this single-group study is unclear.
Intervention
Participants received oral simeprevir 150 mg with oral sofosbuvir 400 mg once a day, from Day 1 up to Week 12. The record describes the study as open-label, so masking was not used.
Comparator
There was no concurrent control arm. The study’s stated objective was to show superiority over a historical control: a composite of SVR12 rates from subpopulations in study HPC3011. The historical composite was to depend on the mix of treatment-naive participants, prior relapsers, prior non-responders, interferon-intolerant participants and other participants enrolled in this study.
Primary question
The primary endpoint was the percentage of participants with SVR12, defined at 12 weeks after actual end of treatment. The registry record does not report an SVR12 estimate, confidence interval or comparison with the historical control. Consequently, the stated superiority question cannot be assessed from the posted results.
3. Trial Design
This was a Phase 3, multicenter, open-label, single-arm study. Allocation is listed as not applicable, and masking as none. All participants received the combination of simeprevir and sofosbuvir; there was no concurrent comparison group. The registry record lists enrollment of 40 and describes the study as completed.
The regimen was oral simeprevir 150 mg with oral sofosbuvir 400 mg once a day, beginning on Day 1 and continuing up to Week 12. The study included treatment-naive and treatment-experienced subjects with chronic genotype 4 hepatitis C virus infection. The registry record lists a start in 2015-01 and primary completion in 2015-12.
The stated objective was to show superiority to a historical control, not to compare randomized groups within this study. The historical control was to be a composite based on observed historical SVR12 rates for simeprevir with pegylated interferon and ribavirin in subpopulations from HPC3011. Its composition was intended to depend on the treatment-history categories among participants enrolled in this study. The registry record does not report the resulting historical-control value or a comparison estimate.
The single-group design can describe outcomes observed among people receiving the regimen, but it cannot by itself separate treatment effects from differences in participant characteristics, care, measurement or time between the study and historical data. The record does not report enough detail to evaluate how the historical composite was constructed or adjusted. It also uses an intent-to-treat definition referring to randomized participants, while describing allocation as not applicable and the design as single-group. That wording leaves the exact analysis population unclear.
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
| Stage | SMV+SOF 12 Weeks |
|---|---|
| STARTED | 40 |
| COMPLETED | 40 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).
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.
| Characteristic | Unit | SMV+SOF 12 Weeks |
|---|---|---|
| Participants analysed | 40 | |
| Age, Continuous | years | 51 (29 to 69) |
| Sex: Female, Male: Female | Participants | 11 |
| Sex: Female, Male: Male | Participants | 29 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12), measured over 12 weeks after EOT.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants with sustained virologic response 12 weeks after end of treatment, called SVR12. The registry record defines SVR12 using hepatitis C virus RNA below the lower limit of quantification, stated as 15 IU/mL, at 12 weeks after actual end of treatment. The definition describes the RNA result as detectable or undetectable below that limit.
SVR12 is a binary outcome: each participant either meets the stated response definition at the specified follow-up or does not. Reporting a percentage summarizes the proportion meeting the definition in the analysis population. It is useful as a virologic endpoint because it evaluates whether the specified RNA criterion is met after treatment has ended, rather than only while treatment is being taken.
The endpoint definition and timeframe are reported, but the primary result is not. The registry record does not report the number meeting the definition, the percentage, its 95% confidence interval, or a comparison against the intended historical control. Therefore, the precision and magnitude of the observed primary outcome cannot be described from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically specific study question: whether a 12-week regimen of simeprevir with sofosbuvir would be superior to a historical control for SVR12 in subjects with chronic genotype 4 hepatitis C. The record also specifies an outcome definition and a 95% confidence interval as the planned measure of dispersion. However, it does not report the primary outcome estimate or confidence interval. The central effectiveness result is therefore not available for statistical interpretation.
The record lists enrollment of 40, but enrollment alone does not show how many participants contributed to the primary endpoint or how many met its definition. The analysis denominator, outcome count, handling of missing endpoint measurements and any exclusions are not reported in the registry record. No percentage or uncertainty measure should be inferred from enrollment or from the safety counts.
The historical comparison requires particular care. It was not a randomized or contemporaneous comparison. The intended control was a composite of historical SVR12 rates from subpopulations in HPC3011, with its value depending on the treatment-history composition of the current study. The registry record does not report the composite rate, the weights or component values, or the estimated difference from it. Without these details and the sponsor’s analysis, neither the direction nor the precision of the planned comparison can be evaluated.
Even if a numerical difference from a historical benchmark were reported, it would be an association across studies rather than a randomized treatment contrast. Differences in who entered the studies, outcome measurement, follow-up or other aspects of care could contribute to a contrast. The registry record does not report adjustment methods that would address these concerns.
The safety record lists zero participants affected by serious adverse events among 40 at risk, and 17 participants affected by other adverse events among 40 at risk. These are safety counts, not evidence about SVR12. Deaths are not reported in the record. The serious-adverse-event count should be read as a description of the recorded safety data, not as proof that serious harm is impossible.
Overall, the registry record allows a description of the design, regimen, endpoint definition and some safety counts. It does not provide the primary efficacy result needed to answer its stated superiority question. The outcome estimates, analysis details and historical comparison are not reported in the registry record.
9. Statistical Methods Explained
What does a percentage endpoint represent?
For a binary endpoint such as SVR12, each participant’s outcome is classified according to whether the endpoint definition is met. A percentage expresses the share of the analyzed participants meeting that definition. It is a summary of observed outcomes in a specified population and at a specified follow-up time. It does not, by itself, establish that treatment caused the outcomes or that the result would apply to people outside the study.
The record gives a primary endpoint definition and timeframe, but no observed SVR12 percentage or endpoint denominator. Thus, there is no response estimate to interpret. The fact that enrollment is listed as 40 does not establish that every enrolled participant was included in the primary analysis or had an evaluable follow-up result.
What would a confidence interval add?
A confidence interval describes statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates that a broader range of values remains compatible with the data and method. An interval is not a guarantee that the true value lies within its bounds, and it does not account automatically for bias in study design or measurement.
The primary endpoint lists a 95% confidence interval as its dispersion measure. No interval bounds are reported in the registry record. As a result, neither the point estimate nor its precision can be assessed. A confidence interval for a single-group percentage would describe uncertainty in that group’s response proportion; it would not remove the limitations of comparing that proportion with a historical control.
How does the historical comparison differ from a concurrent control?
A concurrent control is observed within the same study period, using the study’s procedures and eligibility framework. A historical control uses outcomes recorded in an earlier or separate study. In this trial, the stated benchmark was a composite of historical SVR12 rates from subpopulations in HPC3011, and its value was intended to depend on the mix of treatment-history groups enrolled in the current study.
That design makes the comparison sensitive to how the composite was built and to whether the historical subgroups are comparable to the current participants. Even careful matching of treatment-history categories cannot ensure that every relevant difference between studies has been accounted for. The registry record does not report the composite benchmark, its construction details, or an estimate and uncertainty for the intended comparison. It is therefore not possible to evaluate the numerical superiority claim from this record.
What can a single-group study estimate?
A single-group study can describe outcomes among participants receiving a regimen. It does not provide a randomized within-study estimate of what would have happened to comparable participants under another treatment. The absence of a concurrent comparator leaves the interpretation dependent on external information when a treatment contrast is sought.
Open-label status means masking was not used. That description alone does not establish that outcome measurement was biased. It does mean the record does not describe a masked comparison. More broadly, the registry record does not report the procedures used to collect or adjudicate outcomes, so their possible influence cannot be assessed.
What do the planning assumptions mean?
The registry record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It says the illustration concerns an effect expressed as a fraction of the observed effect. These are planning assumptions, not evidence about the study’s observed efficacy, and they are not identified as the trial’s own design justification.
Equal allocation between two arms does not describe this study’s single-group design. The record does not report the trial’s sample-size justification, an assumed target effect for its own design, or a statistical analysis plan. It also does not report the observed effect needed to interpret the planning illustration. Any sample-size illustration should therefore be read only as a planning exercise, not as observed power or as confirmation that the study could answer its superiority question.
What do adverse-event counts convey?
Counts of participants with events summarize the safety observations recorded for the specified group. They are distinct from the SVR12 endpoint and do not establish a causal comparison with another regimen. The record lists zero participants affected by serious adverse events and 17 affected by other adverse events, each with 40 at risk. It does not report event-level detail for these categories in the information available, and deaths are not reported. General statistical interpretation requires attention to event definitions, observation time and completeness of reporting; those details are not reported in the registry record.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| SMV+SOF 12 Weeks | 40 | 40 | 100.0% | 91.2% to 100.0% | 91.2% to 100.0% | 91.4% to 99.9% |
R code and output
arm <- c("SMV+SOF 12 Weeks")
n <- c(40)
events <- c(40)
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 SMV+SOF 12 Weeks 40 40 100.0 91.2 100.0 91.2 100.0 91.4 99.911. Multiplicity, Missing Data and Analysis Populations
The registry record lists SVR12 as the primary outcome and names secondary outcomes for SVR4, SVR24, on-treatment HCV RNA response, on-treatment failure, viral breakthrough and viral relapse. It also lists seven outcome measures, while reporting zero analyses. The registry record does not report a multiplicity procedure, such as a prespecified way to control the chance of false-positive findings across multiple outcomes or comparisons.
When several outcomes are examined, interpreting each result as if it were the only planned test can overstate the strength of evidence. A prespecified hierarchy or adjustment can address that issue, but no such approach is reported. Since numerical results for these outcomes are not reported, their estimates and any multiplicity-adjusted interpretation cannot be assessed.
Missing-data handling is not reported in the registry record. The number of participants with missing SVR12 measurements, reasons for missingness, imputation choices and sensitivity analyses are not reported. These details matter because the percentage can depend on how participants without an observed outcome are handled.
The stated intent-to-treat population includes randomized participants who received at least 1 dose, while the study is described as single-group with allocation listed as not applicable. The precise analysis population and the relation between enrollment and endpoint analysis are therefore unclear. The registry record does not report a separate per-protocol population or analysis rules for treatment discontinuation. These omissions limit assessment of how completely the reported population would represent everyone enrolled, even if outcome estimates were available.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| SMV+SOF 12 Weeks | 0 | 40 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| SMV+SOF 12 Weeks | 17 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | SMV+SOF 12 Weeks |
|---|---|---|
| Headache | Nervous system disorders | 8 of 40 |
| Asthenia | General disorders | 3 of 40 |
| Catarrh | Respiratory, thoracic and mediastinal disorders | 3 of 40 |
| Erythema | Skin and subcutaneous tissue disorders | 2 of 40 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 40 |
| Constipation | Gastrointestinal disorders | 2 of 40 |
For the group titled SMV+SOF 12 Weeks, the registry record lists 40 participants at risk for serious adverse events and zero affected. It also lists 40 at risk for other adverse events and 17 affected. These figures describe participants recorded with events in the respective categories; they are not a comparison between treatments.
A count of zero recorded participants with serious adverse events does not prove that the regimen has no serious risks. Interpretation depends on the length and completeness of safety observation, event definitions, ascertainment and the size and characteristics of the group. Those details are not reported in the registry record. The record does not list serious adverse-event terms, and deaths are not reported. The absence of listed terms should not be taken as additional evidence beyond the reported affected-participant count.
The 17 participants with other adverse events are distinct from the serious-event count as presented in the registry record, but event types, severity, timing and relationship to study medication are not reported. The counts do not establish whether an event was caused by treatment and do not support comparison with another regimen.
13. What the Result Does, and Does Not, Mean
The record describes a Phase 3, multicenter, open-label, single-arm study of a 12-week course of simeprevir with sofosbuvir in treatment-naive or treatment-experienced subjects with chronic genotype 4 hepatitis C. It specifies SVR12 as the primary endpoint, defines the response timing and RNA criterion, and states an intention to compare the result with a historical composite.
What the posted results do not show is the primary SVR12 estimate, its 95% confidence interval, the historical benchmark or a statistical comparison. The registry record therefore does not establish whether the stated superiority objective was met, nor how precise any primary estimate was. No conclusion about the magnitude of the primary outcome can be drawn from the enrollment figure or adverse-event counts.
The single-group design also matters to interpretation. Outcomes among treated participants can be described, but a historical comparison is vulnerable to differences between the current study and the source studies. The composite benchmark was intended to reflect the current participants’ treatment-history mix, yet its construction and numerical value are not reported. The record also does not report methods for adjusting the comparison or handling missing endpoint data.
The safety counts provide limited descriptive information: zero participants were recorded as affected by serious adverse events, and 17 were recorded as affected by other adverse events, each among 40 at risk. These observations do not quantify every possible harm, establish causation, or show how safety compares with another treatment. Deaths and detailed event information are not reported in the registry record.
Accordingly, the record supports a description of the study question and design, but not a conclusion about the primary efficacy result or a causal treatment effect. That distinction is especially important when a study’s objective invokes superiority but the comparison estimate and its uncertainty are unavailable.
14. Why This Trial Matters Statistically
This trial is statistically notable for pairing a clearly defined binary endpoint with a single-group design and a historical-control objective. Those features make the comparison strategy central to interpretation. The primary endpoint is SVR12, and the intended benchmark was a composite of historical response rates across treatment-history subgroups. Its value was to depend on the mix of participant histories in the study.
That approach highlights a general issue in clinical research: a historical benchmark must be sufficiently comparable to the current study for the contrast to be meaningful. Differences in participant mix and study conduct may influence outcome rates. Matching on treatment-history categories can be relevant, but does not automatically account for other differences. The registry record does not report the composite value, its component rates, how it was constructed, or the comparison estimate, so these features cannot be evaluated numerically.
The study also illustrates why an endpoint definition is not a substitute for a result. The record states how SVR12 was defined and when it was assessed, but does not report the percentage or confidence interval. Without those, readers cannot judge the observed response or its statistical precision. A planned superiority objective alone does not show that superiority was demonstrated.
Finally, the record’s planning illustration uses a two-arm equal-allocation assumption, whereas the trial itself is described as single-group. This distinction reinforces the need to separate planning examples from a study’s actual design and analysis. The sample-size justification and statistical plan are not reported in the registry record. Together, these features make the record useful for understanding the question and its design, while leaving the main statistical conclusion unavailable.
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 trial-specific limitation in the registry record is the absence of the primary SVR12 result and its 95% confidence interval. The outcome definition is available, but the observed percentage, endpoint denominator and comparison with the historical control are not reported. The stated superiority objective therefore cannot be evaluated from the posted results.
The single-arm design offers no concurrent randomized comparator. The planned historical composite depends on the treatment-history mix in this study, but its value, component data, weighting and construction are not reported. Differences between the current study and historical subpopulations could affect the comparison; adjustment methods are not reported.
The registry record does not report missing-data rules, the number of participants with unavailable endpoint measurements, sensitivity analyses, or a detailed analysis population. Its intent-to-treat description refers to randomized participants who received at least 1 dose, although the study is identified as single-group with allocation not applicable. The practical meaning of that population definition is unclear from the record.
The record lists secondary outcomes but does not report their estimates or a multiplicity strategy. It does not report the trial’s statistical analysis plan or sample-size justification. The listed planning illustration assumes equal allocation between two arms, which is not the described trial design; the illustration should not be treated as evidence of observed power or as the study’s own design basis.
Safety interpretation is also limited. The record gives affected-participant counts but does not report detailed event terms, observation duration, event timing or deaths. These omissions constrain assessment of the completeness and context of the safety findings.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Subjects With Chronic Genotype 4 Hepatitis C Virus Infection — NCT02250807.
- Registry record last updated 2016-11-17; status last verified 2016-09.
- Results first posted 2016-11-17.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
NCT02250807 is a completed Phase 3, multicenter, open-label, single-arm study of simeprevir with sofosbuvir in subjects with chronic genotype 4 hepatitis C. The regimen was simeprevir 150 mg and sofosbuvir 400 mg once a day from Day 1 up to Week 12. Enrollment was 40.
The primary endpoint was SVR12, defined using HCV RNA below the stated lower limit of quantification at 12 weeks after actual end of treatment. The study’s stated objective was superiority to a historical composite based on subpopulations from HPC3011. The primary estimate, confidence interval and historical comparison are not reported in the registry record.
Safety counts list zero participants affected by serious adverse events and 17 affected by other adverse events, each among 40 at risk. Deaths are not reported. The record lists secondary virologic outcomes, but their results and the statistical analysis plan are not reported.