A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Renally Impaired Adults With Chronic Hepatitis C Virus Genotype 1 - 6 Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Renally Impaired Adults With Chronic Hepatitis C Virus Genotype 1 - 6 Infection (NCT02651194), a na phase 3 study. The primary outcome is Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12).

2. Clinical Question

3. Trial Design

EXPEDITION-4 was a Phase 3, single-arm, open-label study of ABT-493/ABT-530 in adults with chronic HCV infection and chronic severe renal impairment. The registry record gives an enrollment of 104. It lists no allocation to different groups and no masking. Every participant was assigned to the combination regimen; no concurrent control arm is described.

The regimen was ABT-493/ABT-530, coformulated at 300 mg/120 mg and taken once daily for 12 weeks. The listed primary endpoint was SVR12, assessed 12 weeks after the last actual dose of study drug. The secondary outcomes named in the record were on-treatment virologic failure and post-treatment relapse. The record lists three outcome measures, but does not provide their numerical results in the information available for this analysis.

The study started in 2015-12, had primary completion in 2016-10, and is recorded as completed. These dates describe the registered study timeline; they do not supply additional information about the timing or conduct of individual analyses. Detailed eligibility criteria, baseline characteristics, follow-up completeness, and the reasons for any treatment discontinuation are not reported in the registry record.

Because treatment was not randomized against a control, the design can describe outcomes observed during and after the regimen but cannot isolate a treatment effect by comparison with an untreated or alternatively treated group. Open-label conduct also means masking was not used. The registry record does not report further design details that would establish how subjective outcome assessment was handled.

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: This study included a 35-day screening period.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: all participants who received at least 1 dose of study drug; participants with missing data after backwards imputation were imputed as nonresponders.

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: All participants who received at least 1 dose of study drug (ITT population).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12), 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 treatment (SVR12). The registry definition required plasma HCV RNA to be below the lower limit of quantification 12 weeks after the last dose of study drug. This is a binary outcome: each participant is classified as meeting or not meeting the response definition under the stated analysis rules.

A virologic response endpoint records whether viral RNA is measurable at a specified follow-up time. A sustained-response measure uses a post-treatment assessment rather than an on-treatment measurement, so the timing is part of the endpoint definition. The stated timeframe was 12 weeks after the last actual dose, making the endpoint time-anchored to treatment completion rather than only to the study start.

Reporting a percentage would describe the proportion meeting the definition in the analyzed population. A confidence interval would express uncertainty around that estimated proportion: a narrower interval generally indicates greater precision, while a wider interval indicates less precision. The registry record identifies a 95% confidence interval as the dispersion measure, but its numerical bounds and the SVR12 percentage are not reported in the registry record. The endpoint is therefore defined, but its observed value and precision cannot be assessed from these results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary percentage: participants either satisfy the specified SVR12 definition or do not. A percentage is useful because it expresses the frequency of an outcome in the analyzed group in a readily interpretable form. The estimate still depends on the population definition, the endpoint rules and the handling of missing observations. For this study, the registry record specifies an intent-to-treat population made up of participants who received at least 1 dose, with missing data after backwards imputation counted as nonresponders.

What does a confidence interval add?

A point estimate alone does not convey how much uncertainty surrounds it. A confidence interval gives a range of values compatible with the data under the method used. It is not a guarantee that the true value lies within the reported interval, nor does it account automatically for every source of bias. The registry record names a 95% confidence interval for the primary endpoint, but the numerical estimate and interval limits are not reported in the registry record. The precision of the endpoint therefore cannot be judged.

For a binary outcome, uncertainty is influenced by the amount of information available and by the observed proportion. In general, greater information tends to support more precise estimates; sparse outcome data can produce less precise estimates. These are general statistical principles, not additional findings about this trial. The enrollment figure alone does not reveal the precision of SVR12 because the primary outcome count and missing-data pattern are not reported.

Why does the single-group structure matter?

A single-group design estimates outcomes in the group that received the intervention. In a randomized comparison, treatment groups can be compared under the protection of random assignment, subject to the design and analysis assumptions. Here, the registry record lists no randomized allocation and no control group. Thus, even a reported response percentage would not estimate a contrast against another treatment or a counterfactual outcome. Differences between this group and an external population could reflect eligibility, patient characteristics, follow-up, outcome ascertainment or other factors as well as treatment.

The open-label status means masking was not used. Masking can reduce the possibility that knowledge of treatment assignment influences some aspects of care, reporting or assessment. Its importance depends on the outcome and how it is measured. SVR12 is defined using a laboratory measurement, but the registry record does not provide enough detail to assess laboratory procedures, assessor roles or safeguards against bias. This general explanation does not establish that bias occurred.

How should planning calculations be understood?

Sample-size calculations are planning tools that relate assumptions about an effect, variability, significance level and power to a proposed study size. The registry record describes a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such an illustration is not evidence that the completed single-group trial was designed or analyzed according to those assumptions.

In particular, equal allocation between two arms does not describe this trial’s registered single-group design. A calculation using an observed effect is a hypothetical planning exercise, not an estimate of the study’s observed power. Post-study observed-power calculations do not replace the outcome estimate and its confidence interval. The registry record does not report the trial’s own sample-size justification, and the numerical inputs or outputs of a planning illustration cannot be assessed from the information recorded.

What does over-dispersion mean in general?

For count outcomes, a statistical model may assume a particular relationship between the average event count and its variability. Over-dispersion means the observed variation is greater than that assumption allows. If unaddressed, standard errors can be too small and confidence intervals too narrow. This is a general consideration for count-data methods; the primary endpoint in this study is a binary percentage, and the registry record does not report an analysis involving an over-dispersed count model.

For time-to-event analyses, events and follow-up time are central, and methods may estimate how event rates or event timing differ between groups. No comparative time-to-event analysis is described in the registry record. The named secondary outcomes are virologic failure and relapse, but the record does not report their numerical results, analysis methods or event-time summaries.

Statistical methods should be interpreted in relation to the design, endpoint and missing-data rules, not as isolated labels. The registry record identifies the endpoint form, confidence-interval type and analysis population, but does not report the numerical results or a complete statistical plan. These omissions limit assessment of estimation, precision, model assumptions and robustness.

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("ABT-493/ABT-530")
n      <- c(104)
events <- c(102)
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  ABT-493/ABT-530  104  102  98.1  93.2  99.8  93.3  99.5  93.3  99.4

11. Multiplicity, Missing Data and Analysis Populations

The record identifies SVR12 as the primary endpoint and names on-treatment virologic failure and post-treatment relapse as secondary outcomes. When multiple outcomes are tested or interpreted together, multiplicity can increase the chance of at least one apparently noteworthy result arising by chance. A prespecified hierarchy or adjustment procedure can help address this issue. The registry record does not report whether a multiplicity procedure, endpoint hierarchy beyond the primary designation, or other adjustment was used.

The record lists zero analyses. It does not provide a detailed statistical analysis plan, numerical endpoint results, or information about interim analyses. Whether any additional outcomes or subgroup analyses were planned or conducted is not reported in the registry record. Without that information, the interpretation of a set of outcome findings and any control of false-positive results cannot be assessed.

The intent-to-treat population was defined as participants who received at least 1 dose of study drug. Missing data after backwards imputation were classified as nonresponders for the SVR12 endpoint. This rule makes missing observations count against the response outcome rather than removing them from the endpoint calculation. In general, classifying missing outcomes as failures can produce a lower response estimate than an analysis that excludes those observations, though the size and direction of the difference in this study cannot be determined without the missing-data counts and results.

The record does not report how many participants had missing SVR12 data, the details of the backwards-imputation procedure, or any sensitivity analyses under alternative missing-data assumptions. It also does not report the number assessed at each follow-up time. These gaps matter because the primary endpoint is measured after treatment, and completeness of that assessment affects the evidence available for estimating the response proportion.

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: cardiac failure congestive (2.9%), gastrointestinal haemorrhage (1.9%), pulmonary oedema (1.9%), hypertensive crisis (1.9%), hypertensive cardiomyopathy (1.0%).

The safety record lists 104 participants at risk for serious adverse events and 25 recorded under the serious-event count. It also lists 104 at risk for other adverse events and 54 recorded under that count. These are event-reporting figures for the treated group, not a comparison with an untreated or alternative-treatment group. No comparative risk estimate can be derived from them.

The record lists congestive cardiac failure at 2.9%, gastrointestinal haemorrhage at 1.9%, pulmonary oedema at 1.9%, hypertensive crisis at 1.9%, hypertensive cardiomyopathy at 1.0%, and mitral valve stenosis at 1.0% among the most frequent serious-event terms. The registry record does not provide further context about event onset, duration, severity grading, relatedness assessments or observation time for these terms. The listed percentages should therefore be read as registry safety summaries rather than as causal estimates.

The death count is not reported in the registry record. An absent death value should not be interpreted as evidence that no deaths occurred. More generally, adverse-event counts describe reported events under the record’s definitions and collection procedures; they do not by themselves establish that the study drug caused an event or that an event was unrelated to treatment.

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

The record describes a Phase 3, single-group, open-label study of a 12-week ABT-493/ABT-530 regimen in adults with chronic HCV infection and chronic severe renal impairment. It defines SVR12 as the primary endpoint and specifies a post-treatment assessment based on HCV RNA below the lower limit of quantification. It also identifies an intent-to-treat population and a rule for counting missing endpoint data as nonresponders after backwards imputation.

Those design and endpoint details explain what the study intended to measure. They do not provide the primary result. The numerical SVR12 percentage, confidence-interval bounds, and counts meeting or not meeting the definition are not reported in the registry record. Accordingly, the response frequency and its precision cannot be stated. The secondary outcome names are listed, but their numerical results are also not reported.

Even if a response estimate were available, the single-group design would support a description of outcomes among treated participants, not a randomized comparison. Without a control group, it cannot determine how outcomes would differ under another regimen or without treatment. Open-label conduct and the absence of further assessment details also constrain evaluation of possible ascertainment influences, although the record does not establish that such bias occurred.

The safety counts and listed serious-event terms provide some descriptive information, but they do not establish causation or comparative safety. The death count and additional details about safety ascertainment are not reported in the registry record. A complete interpretation would require the missing numerical efficacy results, their uncertainty, fuller follow-up and analysis information, and suitable comparative evidence for causal claims. None of these qualifications changes the registered study question; they define what can and cannot be concluded from the record.

14. Why This Trial Matters Statistically

This study is statistically notable for the combination of a clearly defined post-treatment virologic endpoint and a single-group design in a population described as having chronic severe renal impairment. The endpoint’s timing and threshold make its intended classification explicit: response was based on HCV RNA below the lower limit of quantification 12 weeks after the last actual dose. Such precise endpoint definitions are necessary for reproducible interpretation.

The record also makes an important analysis choice explicit. The primary population included participants who received at least 1 dose, and missing data after backwards imputation were treated as nonresponse. This illustrates how missing-data rules are part of an endpoint’s operational definition, rather than a minor technical detail. Without the missing-data frequency and sensitivity analyses, readers cannot determine how much that rule influenced the estimate.

At the same time, the study structure places a firm boundary on interpretation. A single-group trial can describe outcomes during a regimen, but it does not have a randomized control group to estimate a comparative effect. This distinction is fundamental when moving from a response proportion to a causal claim. The registry record’s lack of a numerical primary result further limits what can be inferred: neither the response level nor its precision is available to assess.

The available safety summaries also demonstrate why descriptive counts and causal comparisons should not be conflated. Counts and term percentages can flag what was recorded, but interpretation requires context on event definitions, follow-up and comparison. Overall, the statistical value of the record lies in documenting the study framework and outcome rules, while its missing results and comparative limitations leave the central efficacy estimate unquantified.

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 consequential limitation in the registry record is that it does not report the numerical primary endpoint result. Although SVR12 is defined and a 95% confidence interval is identified as the dispersion measure, neither the response percentage nor its interval bounds are reported. The efficacy estimate and its precision therefore cannot be evaluated.

The single-group, open-label design has no randomized comparator. As a result, the study record cannot establish a comparative effect or separate treatment-associated outcomes from other influences. The registry record does not report additional design details that might clarify outcome assessment, adherence, follow-up completeness or handling of protocol deviations.

Several details needed to assess the analysis are also absent. The record does not report the sample-size justification for the trial, a complete statistical analysis plan, any multiplicity procedure, interim analyses, missing-outcome counts, or sensitivity analyses for missing data. The stated rule that missing data after backwards imputation count as nonresponders is informative, but the actual impact of that rule cannot be assessed without further results.

Safety interpretation is limited by the absence of a comparison group and by missing context about ascertainment, event timing, relatedness and follow-up. The death count is not reported in the registry record. Further population characteristics, including the distribution of HCV genotypes and details of renal impairment, are also not reported. These omissions constrain generalization and prevent a fuller assessment of how closely the registered study population matches other clinical populations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Renally Impaired Adults With Chronic Hepatitis C Virus Genotype 1 - 6 Infection — NCT02651194.
• Registry record last updated 2017-10-16; status last verified 2017-09.
• Results first posted 2017-10-16.
• 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

EXPEDITION-4 was a completed Phase 3, single-group, open-label study of ABT-493/ABT-530 in adults with chronic HCV genotypes 1–6 and chronic severe renal impairment. The registry records enrollment of 104 and a once-daily coformulated dose of 300 mg/120 mg for 12 weeks.

The primary endpoint was SVR12, defined using HCV RNA below the lower limit of quantification 12 weeks after the last actual dose. The analysis population included participants who received at least 1 dose, with missing data after backwards imputation counted as nonresponders. The numerical primary result and confidence-interval bounds are not reported in the registry record. Safety figures include 25 recorded serious adverse events and 54 other adverse events, each with 104 at risk; these are descriptive, single-group data.