Evaluate the Efficacy and Safety of TG-2349 in Subjects With Hepatitis C Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate the Efficacy and Safety of TG-2349 in Subjects With Hepatitis C Infection (NCT02340962), a randomized phase 2 study. The primary outcome is Proportion of Subjects Achieving Sustained Viral Response at 12 Weeks After the End of Treatment..

2. Clinical Question

The record describes a Phase 2, multicenter, randomized, open-label, dose-ranging study. It enrolled 25 participants and was completed. The primary endpoint focuses on the durability of the virologic response after the treatment period, rather than only a measurement taken while treatment was ongoing. The posted group results are counts of participants meeting the response criterion: 11 of 13 in the 200 mg group and 10 of 12 in the 400 mg group. The registry record does not report a placebo group or a group receiving the background drugs without TG-2349.

3. Trial Design

This was a randomized, open-label, parallel-group Phase 2 trial of TG-2349 in combination with interferon or peg-interferon and ribavirin. The two groups differed in the TG-2349 dose: Group I received 200 mg and Group II received 400 mg. The study description identifies a dose-ranging comparison among treatment-naïve East Asian subjects with chronic hepatitis C virus genotype 1b infection. The registry record lists TG-2349, ribavirin, and interferon alfa-2a as interventions; the group descriptions refer to interferon or peg-interferon with ribavirin.

Enrollment was 25. The posted primary outcome results list 13 participants in the 200 mg group and 12 in the 400 mg group. The trial began in 2015-05, had primary completion on 2016-08-12, and is recorded as completed. The registry record does not report the randomization sequence method, allocation concealment, masking of outcome assessors, or further operational detail about the study sites. The study is explicitly described as open-label, so participants and study personnel were not masked to assigned dose.

The primary outcome was sustained viral response 12 weeks after treatment ended, following 12-week treatments. Secondary outcome descriptions include response at other follow-up times, measures of HCV RNA, virologic failure and relapse, and ALT normalization. The registry record does not report the original design assumptions or sample-size justification. The posted planning illustrations are based on the observed effect and are not evidence of the trial’s original design rationale.

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: Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

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: Full Analysis Set (FAS) population includes subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Subjects Achieving Sustained Viral Response at 12 Weeks After the End of Treatment., measured over 12 weeks after the end of treatment (SVR12), after 12-week treatments.

The primary endpoint is the proportion of subjects achieving sustained viral response 12 weeks after the end of treatment, designated SVR12. The registry describes this as the proportion with HCV RNA below the lower limit of quantification, with target detected or target not detected, at that follow-up point. The stated timeframe is 12 weeks after the end of treatment, following 12-week treatments. The primary analysis population is the Full Analysis Set: subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs.

As a general statistical concept, a sustained response endpoint evaluates whether the measured virologic response persists into follow-up after treatment ends. It is distinct from an on-treatment measurement, which records HCV RNA while treatment is being given. Reporting the endpoint as a proportion makes the result interpretable as the number of participants meeting the response definition relative to the participants in the analysis group. Here, the posted results are counts: 11 of 13 in the 200 mg group and 10 of 12 in the 400 mg group.

The registry record does not report additional operational details about assay handling or how a missing SVR12 assessment was classified. The endpoint description alone therefore does not establish how every possible incomplete or ambiguous measurement was handled.

7. Results Posted in the Registry

• 400 mg TG-2349: 83.3% (10/12) versus 84.6% (11/13) on control; risk difference -1.3 percentage points (95% CI -30.1 to 27.5), risk ratio 0.98 (0.70–1.39); unadjusted two-proportion z-test p = 0.930.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the risk difference describe?

As a general statistical concept, a risk difference subtracts one group’s event proportion from the other group’s event proportion. It expresses the contrast on the absolute probability scale. The posted comparison is for the 400 mg group relative to the 200 mg group. A value near zero indicates that the observed proportions are close; the sign indicates the direction of the contrast under that ordering. The posted estimate is close to zero, and its confidence interval includes zero. The result therefore does not precisely distinguish a small difference from no difference or from a difference in the other direction.

What does a confidence interval add?

A confidence interval describes the range of values compatible with the observed data under the statistical method used. As a general explanation, narrower intervals indicate greater precision, while wider intervals indicate less precision. A confidence interval is not a guarantee that the true effect lies within its endpoints, nor does it assign a probability to particular values after the data have been observed. For this comparison, the interval spans both negative and positive risk differences. That breadth is important alongside the point estimate: the estimate alone would conceal how uncertain the contrast is.

How should the p-value be understood?

The unadjusted p-value is 0.93. In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, and it is not a measure of the size or clinical importance of an effect. A large p-value does not prove that the groups are identical. Here, the p-value should be considered together with the event counts and the broad confidence interval, rather than treated as a stand-alone verdict.

What does the participant-count outcome mean?

The primary outcome is binary at the participant level: each participant either meets the SVR12 definition or does not, according to the endpoint rules. The posted arm results are counts of participants meeting that definition, accompanied by group sizes. A binary outcome allows a comparison of proportions, but the amount of information depends strongly on how many participants contribute to each group. With small groups, each participant represents a relatively substantial part of the observed group result, and estimates can change noticeably with only a few outcomes differing.

What can be concluded from randomization and open-label conduct?

Random allocation is intended, as a general design principle, to make treatment groups comparable on average with respect to both measured and unmeasured factors. It does not ensure perfect balance in a small trial. The registry record identifies the study as randomized and open-label, but does not report the sequence-generation or allocation-concealment methods. Open-label conduct means assigned dose was not masked. The record does not explain whether endpoint assessors were masked or how the laboratory outcome was processed. These missing design details constrain assessment of potential bias, though they do not change the arithmetic of the posted group counts.

Why can dispersion matter in other outcome types?

As a general statistical concept, dispersion describes variation in measurements around a typical value. For count outcomes, over-dispersion means that the observed variation is greater than a chosen model would expect. Ignoring over-dispersion can make uncertainty estimates too small and confidence intervals too narrow. That issue is not the defining feature of this primary endpoint, which is recorded as a participant count meeting a binary response criterion. The registry record does list other outcomes involving viral-load measurements, but does not provide their posted results or analysis methods. It does not report a dispersion parameter for the primary outcome.

What details of the analysis are unavailable?

The registry record does not report the specific test or model used for the primary comparison, the method for constructing its confidence interval, or an analysis plan. It also does not report whether adjustment for covariates was used, how missing primary outcomes were handled, or whether any interim analyses were planned or conducted. Those details should not be inferred from the fact that an unadjusted p-value and risk-difference comparison are posted. The comparison can be described, but its full analytic provenance is not reported in the registry record.

10. Confidence Intervals and Precision

The point estimate for the risk difference is close to zero, but the confidence interval is broad and crosses zero. This means the posted data are compatible with more than one interpretation: a modest advantage for either dose group, or a small difference. The interval is therefore more informative about uncertainty than the point estimate alone. It does not support a precise claim that the two doses have identical response proportions, and it does not establish that one dose has a clear advantage.

As a general statistical explanation, precision reflects how tightly the data constrain an estimate. It depends on the amount of information available and on the variability of the outcome. For a binary endpoint, the group sizes and numbers of responses contribute to that information. The posted group results are 11 of 13 and 10 of 12, so the primary comparison is based on small groups. With few participants, observed proportions can be sensitive to the outcome of an individual participant, and the confidence interval can remain wide even when the point estimates look similar.

The interval’s inclusion of zero is consistent with the unadjusted p-value of 0.93, but neither item proves there is no difference. An equivalence or non-inferiority claim would require a suitable design and prespecified decision criteria; these are not reported in the registry record. The width of the interval also cautions against treating the observed contrast as a stable estimate for other populations or settings. The registry record does not report a confidence-interval method, so precision should be interpreted from the posted interval without assuming a particular calculation procedure.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size planning figures are participants per arm, not total events. They are illustrations based on the observed effect, not the trial’s original design assumptions. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The registry record does not report the original sample-size justification or the assumptions used when the trial was designed.

The 80% power column gives the planned number of participants per arm under the stated assumptions for a design with an 80% chance of detecting the specified effect if that effect is the true one and the assumptions hold. The 90% power column uses a higher chance of detection under those same conditions and therefore requires more participants per arm for each listed effect size. These are planning calculations, not a description of the participants enrolled in this trial.

The rows consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The listed participants per arm for 80% power are 12,852, 22,663, and 50,574, respectively; for 90% power they are 17,204, 30,339, and 67,703, respectively. Smaller effects require more participants because a subtler group difference is harder to distinguish from random variation. These planning figures are not observed power and should not be read as evidence about the probability that this completed study detected an effect.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.846; treatment proportion p₁ = 0.833; average p̄ = 0.840.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5188 = 1.0168.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5187 = 0.4366.
4. n = (1.0168 + 0.4366)² / (-0.0128)² = 12,851.4, rounded up to 12,852 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.846153846153846                          # control proportion
p1 <- 0.833333333333333                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2340962)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 12,852 (80% power), 17,204 (90% power)
 75% of observed effect: n per arm = 22,663 (80% power), 30,339 (90% power)
 50% of observed effect: n per arm = 50,574 (80% power), 67,703 (90% power)
power.prop.test: 12851.4 
Simulated power at n = 12,852 per arm: 0.802 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and seven posted secondary outcomes. The secondary outcome descriptions cover SVR at additional follow-up times, HCV RNA thresholds and measurements, virologic failure and relapse, ALT normalization, and change in HCV RNA. The record lists eight outcome measures overall. It does not report results for those secondary outcomes in the posted information used for this analysis.

When a study examines multiple outcomes or multiple time points, the chance of at least one apparently notable result can increase. As a general statistical concept, multiplicity procedures can control that risk, while a prespecified hierarchy can identify which comparisons are confirmatory and which are exploratory. The registry record does not report a multiplicity adjustment, an outcome-testing hierarchy, or a statistical analysis plan. It is therefore not possible to determine from the record whether or how multiplicity was addressed. The unadjusted p-value should be understood as unadjusted, not as a result known to account for other outcomes or analyses.

The Full Analysis Set is defined as subjects with genotype 1b HCV infection who were enrolled and received at least one dose of study drugs. The endpoint description identifies this as the population for the primary outcome. The record does not report how missing SVR12 measurements were classified, whether any participants were excluded after receiving a dose, or how deviations from treatment were handled. It also does not provide participant-level missingness details.

The registry outcome-analysis count is 0, while arm-level results and a comparison are posted for the primary outcome. This leaves the analysis reporting incomplete: the record gives useful outcome summaries but does not document a full set of statistical analyses. The analysis populations for the secondary outcomes, any sensitivity analyses, and the handling of missing data are not reported in the registry record. These omissions limit assessment of selective reporting and robustness.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lower limb fracture (8.3%), bladder cancer (8.3%), neutropenia (7.7%), cellulitis (7.7%).

The registry reports serious adverse events for Group I and Group II separately. In Group I, 2 serious adverse events were recorded among 13 participants at risk; in Group II, 2 were recorded among 12 participants at risk. The record reports 0 deaths in each group. For other adverse events, the reported affected counts are 13 among 13 at risk in Group I and 12 among 12 at risk in Group II. These are safety summaries and should not be conflated with the primary SVR12 endpoint.

The listed serious adverse event terms include Lower limb fracture at 8.3%, Bladder cancer at 8.3%, Neutropenia at 7.7%, and Cellulitis at 7.7%. The record does not clarify in this summary how these terms map to individual groups or whether one participant could contribute more than one term. These percentages should therefore be read as reported terms, not assigned to a dose group without supporting detail.

As a general statistical point, adverse-event counts describe events or affected participants according to the registry’s reporting conventions; the conventions matter when interpreting totals and overlap. The record does not provide detailed event timing, severity grading beyond the serious-event classification, duration, relationship to study drugs, or group-specific term counts. The small groups also limit how precisely these figures describe safety. The summaries do not, on their own, establish comparative safety.

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

The primary result describes SVR12 counts in a small randomized dose comparison: 11 of 13 participants in the 200 mg TG-2349 group and 10 of 12 in the 400 mg group met the stated response criterion. The posted risk-difference estimate is close to zero, the confidence interval spans zero, and the unadjusted p-value is 0.93. Together, these statistics show that the observed group results were similar, while leaving considerable uncertainty about the underlying difference.

This does not establish that the doses are equivalent, that the true difference is zero, or that either dose is superior. It also does not answer whether the combination is better than a regimen without TG-2349, because the record does not list such a comparator. The outcome is a virologic measure at a specified follow-up time; it is not by itself a complete assessment of health outcomes or treatment safety.

The findings apply to the population and combination described in the record: treatment-naïve East Asian subjects with chronic HCV genotype 1b infection who received at least one dose of study drugs, with SVR12 assessed in the Full Analysis Set. Generalization beyond that group, the trial setting, or the treatment regimen is not established by these data. The registry record does not report sufficient detail about missing outcomes, the analysis plan, or the method used for the comparison to resolve those uncertainties.

The safety summary is separate evidence. Serious adverse events and other adverse events were reported in both groups, with no deaths recorded. The event-term information does not provide enough detail to attribute each listed term to a particular group or infer a causal relationship. The efficacy and safety summaries should be interpreted as descriptive trial findings, not as individualized treatment guidance.

16. Why This Trial Matters Statistically

This trial illustrates why an observed similarity between group results is not the same as a precise conclusion of no difference. The primary counts are close, but the comparison’s confidence interval spans values in both directions. Looking at the interval alongside the point estimate prevents a reader from treating the observed contrast as more certain than the data support. The unadjusted p-value also needs this context: it does not quantify the probability that the doses are identical.

The trial is a randomized, open-label dose-ranging study with a clearly defined primary response time point. That structure gives a direct comparison between two TG-2349 doses within a shared combination regimen. At the same time, the small group sizes mean that the primary estimate is imprecise, and the absence of a no-TG-2349 comparator limits what the study can say about the contribution of TG-2349 itself.

The record also makes visible an important distinction between observed trial data and planning calculations. The sample-size illustrations use the observed effect and stated assumptions; they are not a retrospective measure of power and do not disclose why the original trial enrolled its participants. Separating those purposes helps avoid treating a planning exercise as a design justification.

Finally, the registry record includes a defined Full Analysis Set and several secondary outcome descriptions, but does not report a complete analysis plan, missing-data handling, or secondary results in this summary. Those gaps matter because statistical interpretation depends not only on estimates, but also on how outcomes and analyses were specified and carried out. The trial therefore offers a useful example of reading outcome counts, uncertainty, design context, and reporting limitations together.

17. 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.

Several trial-specific limitations affect interpretation. The study was open-label, and the registry record does not report whether outcome assessors were masked. It identifies randomization but does not describe sequence generation or allocation concealment. The small groups—13 participants in the 200 mg group and 12 in the 400 mg group—produce an imprecise primary comparison, as reflected by a confidence interval that includes effects in either direction.

The comparison concerns two TG-2349 doses given with interferon or peg-interferon and ribavirin. The registry record does not list a placebo group or a background-treatment-only group, so the posted comparison cannot isolate the effect of TG-2349 versus no TG-2349. The record also does not report whether the choice between interferon and peg-interferon varied by participant or group, or provide further regimen details.

Important statistical details are not reported in the registry record, including the original sample-size rationale, the primary analysis method, the confidence-interval method, multiplicity procedures, and missing-data handling. The listed secondary outcomes do not have corresponding results in the posted summary used. The adverse-event term summary lacks detail about group attribution, timing, and relationship to study drugs. These reporting gaps limit assessment of robustness, selective reporting, and safety comparisons. The findings should be understood in the context of this specific population, trial design, and combination regimen.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Evaluate the Efficacy and Safety of TG-2349 in Subjects With Hepatitis C Infection — NCT02340962.
• Registry record last updated 2023-07-14; status last verified 2018-09.
• Results first posted 2018-10-12.
• 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.

21. Record Summary

The registry record describes a completed, randomized, open-label, parallel-group Phase 2 dose-ranging study of TG-2349 with interferon or peg-interferon and ribavirin in treatment-naïve East Asian subjects with chronic hepatitis C genotype 1b infection. Enrollment was 25. The groups received 200 mg or 400 mg TG-2349. The primary outcome was SVR12 in the Full Analysis Set.

The posted primary counts were 11 of 13 in the 200 mg group and 10 of 12 in the 400 mg group. The comparison has a risk-difference confidence interval spanning zero and an unadjusted p-value of 0.93. The record also lists seven secondary outcomes and adverse-event summaries. The original sample-size justification, detailed analysis plan, missing-data procedures, and secondary outcome results are not reported in the registry record.