A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-administration of ABT-493 and ABT-530 With and Without Ribavirin in Subjects With HCV Genotype 1, 4, 5, and 6 Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-administration of ABT-493 and ABT-530 With and Without Ribavirin in Subjects With HCV Genotype 1, 4, 5, and 6 Infection (NCT02243280), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks Post-treatment.

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, multicenter study with a parallel design and non-randomized allocation. The registry record reports enrollment of 174 and describes the study as having two parts. The study began in 2014-08, had primary completion in 2016-02, and is listed as completed. The record does not report how participants were allocated to the arms or whether allocation followed a formal rule.

The study evaluated ABT-493 with ABT-530 in participants with chronic HCV genotype 1, 4, 5, or 6 infection. The listed arms varied by dose, duration, genotype, and cirrhosis status. Arms A and B were for genotype 1 without cirrhosis, with ABT-493 200 mg once daily and different ABT-530 doses for 12 weeks. Arm F used the same stated ABT-493 dose and ABT-530 120 mg once daily for genotype 1 participants with compensated cirrhosis. Arm I was for genotypes 4, 5, and 6 without cirrhosis, using ABT-493 300 mg and ABT-530 120 mg once daily for 12 weeks. Arm K used ABT-493 300 mg and ABT-530 120 mg once daily for 8 weeks in genotype 1 participants without cirrhosis.

Other listed arms were never opened following a sponsor decision. Ribavirin was initially planned in the protocol, but the registry record states that it was not administered in any arm. Because the study was not randomized and the arms do not represent like-for-like groups, between-arm outcome differences cannot be attributed to treatment choice alone. The registry record does not report a detailed statistical analysis plan, the allocation process, or an intended primary comparison.

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: Safety population: all participants who received at least 1 dose of study drug. Two participants assigned to Arm I received the incorrect dose of study drug throughout their participation in the study (ABT-493 200 mg QD instead of 300 mg) and are therefore included in Arm A instead of Arm I in the safety population.

Only the first 6 of 11 groups are shown.

Enrolled

Treated

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat population: all participants who received at least 1 dose of study drug

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety population: all participants who received at least 1 dose of study drug. Two participants assigned to Arm I received the incorrect dose of study drug throughout their participation in the study (ABT-493 200 mg QD instead of 300 mg) and are therefore included in Arm A instead of Arm I in the safety population.

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks Post-treatment, measured over 12 weeks after the last actual dose of study drug.

The primary endpoint was the percentage of participants with sustained virologic response 12 weeks after the last actual dose of study drug. The registry record defines response as plasma HCV RNA below the lower limit of quantification at that time. It identifies the analysis population as participants who received at least 1 dose of study drug.

This is a binary endpoint at the participant level: each participant either meets the stated response definition or does not. Reporting the percentage expresses how common the endpoint was within the assessed group. As a general statistical concept, a confidence interval describes uncertainty around an estimated percentage; the registry lists a 95% confidence interval as the dispersion measure for this outcome. The numerical percentage and its interval are not reported in the registry record, so the precision of the observed response estimate cannot be assessed from these registry entries.

SVR is used as a virologic outcome because it captures whether HCV RNA is below the specified measurement threshold at a defined post-treatment follow-up point. It should be read according to the endpoint definition and timing, rather than as a direct measure of every aspect of health or safety. The record also lists secondary outcomes concerning SVR 4 weeks post-treatment, on-treatment virologic failure, and post-treatment relapse. Their numerical results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a percentage, so its basic statistical form is a proportion: participants meeting the response definition relative to those assessed for the endpoint. The registry record defines response as HCV RNA below the lower limit of quantification 12 weeks after the last actual dose. It also specifies that the intended population is participants who received at least 1 dose of study drug. The record does not report the observed numerator or the arm-specific denominator for this outcome, so a percentage cannot be interpreted from the registry entries.

What does the confidence interval convey?

The registry identifies a 95% confidence interval as the measure of dispersion for the primary percentage. As a general statistical explanation, a confidence interval gives a range of values compatible with the data under the method used. A narrower interval indicates greater precision, while a wider interval indicates less precision. The interval does not remove possible bias from study design, selection, missing outcomes, or measurement. No numerical confidence intervals are reported in the registry record, so the precision of the endpoint estimate cannot be judged.

What does the non-randomized design imply?

Randomization is a method for balancing participant characteristics between groups in expectation. This study is explicitly listed as non-randomized. Its arms also differ in regimen and participant eligibility, including genotype and cirrhosis status. As a general statistical matter, such differences can make unadjusted comparisons difficult to interpret: an observed contrast may combine treatment differences with group differences. The registry record states that arms are not a like-for-like control comparison. It does not report an adjusted analysis that would address these differences, and it lists no analysis entries.

How should the sample-size illustrations be read?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations are framed around detecting a stated fraction of the observed effect. For non-time-to-event outcomes, the stated output convention is participants per arm for 80% power or 90% power. These are planning calculations, not observed trial results and not observed power. The numerical effect, sample-size illustration values, and specific fractions are not reported in the registry record details, so they cannot be interpreted. General statistical context: planning estimates depend on assumptions about the effect to detect, variability, significance level, allocation, and method. They do not show that a study achieved its intended precision or that an effect was present.

Why does outcome type matter?

The endpoint is binary at the participant level because each participant either satisfies the SVR definition or does not. Proportion estimates are sensitive to the number of participants with outcome information, especially when groups are small. General statistical context: the number of events and the denominator both inform precision. An estimate based on few outcome events may be uncertain even when its point estimate appears clear. The registry record does not give the primary endpoint event counts or denominators by arm, so this consideration cannot be quantified for the study.

The registry also lists secondary outcomes for SVR 4 weeks post-treatment, on-treatment virologic failure, and post-treatment relapse. It reports four outcome measures overall, but gives no numerical results for these secondary endpoints in the registry record. A complete interpretation would require their definitions, observed counts or percentages, denominators, and uncertainty estimates. Those details are not reported in the registry record details.

Finally, the study’s open-label status and non-randomized allocation are design features, while a confidence interval is a measure of sampling uncertainty. These address different issues. General statistical explanation: an interval can characterize uncertainty under a statistical model, but it does not correct systematic differences between groups or settle whether missing data have biased an estimate. The registry record does not report enough information about analysis methods, missing observations, or comparative adjustment to assess those issues.

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", "Arm B", "Arm F", "Arm I", "Arm K")
n      <- c(40, 39, 27, 34, 34)
events <- c(40, 38, 26, 34, 33)
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  40  40  100.0  91.2  100.0  91.2  100.0  91.4  99.9
ARM  Arm B  39  38  97.4  86.5  99.9  86.8  99.5  86.8  99.4
ARM  Arm F  27  26  96.3  81.0  99.9  81.7  99.3  81.7  99.1
ARM  Arm I  34  34  100.0  89.7  100.0  89.8  100.0  90.0  99.9
ARM  Arm K  34  33  97.1  84.7  99.9  85.1  99.5  85.1  99.3

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary endpoint and secondary outcomes involving SVR 4 weeks after treatment, on-treatment virologic failure, and post-treatment relapse. The record also reports four outcome measures overall. When several outcomes or comparisons are examined, general statistical context is that the chance of a false-positive finding can increase if no multiplicity strategy is used. The registry record does not report whether multiplicity was addressed, how outcomes were prioritized beyond identifying the primary endpoint, or whether any interim analyses were conducted.

Missing-data methods are not reported in the registry record. The primary population is defined as the intention-to-treat population comprising participants who received at least 1 dose of study drug, but the record does not state how participants without an endpoint measurement were handled. It also does not report the number with missing primary outcome data or whether any imputation or sensitivity analyses were used. General statistical context: the treatment of missing outcomes can affect a percentage estimate, particularly if missingness is related to response or group membership.

The registry lists 174 enrolled participants, but the number included in the primary endpoint analysis and the group-specific denominators are not reported in the registry record. The record lists no analysis entries. It therefore does not provide enough information to assess the analysis population actually used, missing-data assumptions, or the handling of multiple outcomes and comparisons.

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: pulmonary embolism (3.7%), adenocarcinoma (2.9%), prostate cancer metastatic (2.4%).

The registry safety figures list participants at risk and participants affected by serious adverse events and other adverse events for Arms A, B, F, I, and K. In Arm A, 1 participant among 42 at risk was affected by a serious adverse event, and 22 among 42 were affected by other adverse events. In Arm B, no participants among 39 at risk were affected by a serious adverse event, and 22 among 39 were affected by other adverse events. In Arm F, 1 among 27 at risk was affected by a serious adverse event, and 9 among 27 were affected by other adverse events. In Arm I, no participants among 32 at risk were affected by a serious adverse event, and 20 among 32 were affected by other adverse events. In Arm K, 1 among 34 at risk was affected by a serious adverse event, and 19 among 34 were affected by other adverse events.

These are descriptive counts, not randomized safety comparisons. The arms differed in participant groups and regimens, and the registry record cautions that they are not like-for-like controls. The listed serious adverse event terms include pulmonary embolism at 3.7%, adenocarcinoma at 2.9%, and metastatic prostate cancer at 2.4%; the record does not specify the denominators for these percentages in the registry record. Death counts are not reported in the registry record. The figures should not be treated as a complete assessment of comparative risk.

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

The registry record establishes that the study evaluated combinations of ABT-493 and ABT-530 in chronic HCV genotype 1, 4, 5, and 6 infection. It defines the primary endpoint as SVR 12 weeks after the last actual dose, with response meaning HCV RNA below the lower limit of quantification. It also specifies the intended endpoint population and lists secondary virologic outcomes. These details clarify what the study set out to measure.

However, the numerical primary and secondary efficacy results are not reported in the registry record details. Without observed percentages, event counts, denominators, and confidence intervals, the endpoint magnitude and precision cannot be described. The study’s enrollment figure does not substitute for an endpoint analysis denominator, and no treatment effect can be inferred from enrollment or the regimen descriptions alone.

The record also does not establish that one regimen performed better than another. Allocation was non-randomized, arms differed in regimen and eligibility, and the registry record cautions that they are not like-for-like control comparisons. General statistical context: an observed difference between non-randomized groups can reflect differences in participants or other factors, in addition to any treatment-related difference. No adjusted comparative analysis is reported in the record.

The safety figures document serious and other adverse event counts for the listed arms, but they are descriptive and do not provide a randomized basis for comparing risks. The registry record does not report death counts in the registry record. These data do not amount to a complete account of safety or establish whether the regimens are beneficial or harmful.

In short, the registry record supports a description of the study design, endpoint definition, and selected safety counts. It does not support conclusions about the size of the virologic response, the certainty of an efficacy estimate, or comparative treatment effects.

14. Why This Trial Matters Statistically

This study illustrates why design information is essential when reading clinical trial results. A parallel-arm structure alone does not make groups directly comparable. The registry identifies this study as non-randomized and explicitly warns that its arms are not like-for-like controls. The regimens were also studied in different genotype and cirrhosis groups, with variation in dose and duration. These features limit what can be concluded from simple arm-to-arm contrasts.

The endpoint definition is another important statistical feature. SVR is expressed as a percentage of participants meeting a laboratory threshold at a specified post-treatment time. Interpreting such an estimate requires both the event count and the denominator, together with an uncertainty measure. The registry record identifies a 95% confidence interval as the dispersion measure but does not report the numerical endpoint results or intervals in the registry record. This makes clear that an outcome definition is not itself an outcome estimate.

The study also shows the difference between a protocol plan and what was actually administered: ribavirin was initially planned, but the registry record states that it was not administered in any arm. Several listed arms were never opened following a sponsor decision. Reading the actual arm descriptions is therefore important when distinguishing planned regimens from those represented in the listed safety groups.

Finally, planning illustrations based on observed effects are not evidence of observed power or a substitute for reported estimates. They are useful only as conditional planning calculations under stated assumptions. Without the numerical efficacy findings and analysis details, the statistical record remains informative about design and measurement but does not permit a quantitative assessment of the primary effect.

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 for interpretation is that numerical efficacy results are not reported in the registry record details. The primary outcome percentage, its confidence interval, the endpoint event counts, and the analyzed denominators are unavailable. The secondary outcome results are also not reported. As a result, the magnitude and precision of the study’s virologic outcomes cannot be assessed.

The non-randomized, open-label design limits comparative interpretation. The registry record states that arms are not like-for-like control comparisons, and arm eligibility and regimens varied by genotype, cirrhosis status, dose, and duration. The record does not report an adjustment method or a detailed statistical analysis plan. It also does not report the allocation process.

The protocol initially planned ribavirin, but it was not administered in any study arm. Several listed arms were never opened following a sponsor decision. These registry entries mean that the listed planned arms should not be mistaken for groups that necessarily contributed data. The registry record does not give arm-specific efficacy analysis counts to clarify the contribution of each group.

Methods for missing outcomes, multiplicity, interim analyses, and sensitivity analyses are not reported in the registry record. Death counts are not reported in the safety details. The serious adverse event term percentages are provided without denominators in the registry record. These omissions restrict assessment of outcome completeness and the context for safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-administration of ABT-493 and ABT-530 With and Without Ribavirin in Subjects With HCV Genotype 1, 4, 5, and 6 Infection — NCT02243280.
• Registry record last updated 2021-07-13; status last verified 2021-07.
• Results first posted 2017-04-06.
• 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

The registry record describes a completed Phase 2, open-label, multicenter, non-randomized, parallel study of ABT-493 and ABT-530 in chronic HCV genotype 1, 4, 5, and 6 infection. Enrollment is listed as 174. The study began in 2014-08 and reached primary completion in 2016-02.

The primary endpoint was SVR 12 weeks after the last actual dose, defined as HCV RNA below the lower limit of quantification. Numerical efficacy results are not reported in the registry record details. Several arms were never opened, and ribavirin was not administered in any arm despite being initially planned. The listed safety counts are descriptive; the record cautions that the arms are not like-for-like controls.