A Multipart, Open-label Study to Evaluate the Safety and Efficacy of ABT-450/r/ABT-267 With and Without ABT-333 Coadministered With and Without Ribavirin in Adult With Genotype 1 or 4 Hepatitis C Virus (HCV) Infection and Human Immunodeficiency Virus, Type 1 Coinfection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multipart, Open-label Study to Evaluate the Safety and Efficacy of ABT-450/r/ABT-267 With and Without ABT-333 Coadministered With and Without Ribavirin in Adult With Genotype 1 or 4 Hepatitis C Virus (HCV) Infection and Human Immunodeficiency Virus, Type 1 Coinfection (NCT01939197), a randomized phase 2, phase 3 study. The primary outcome is Percentage of Participants in GT1 Analysis Group 1 in Part 2 Achieving Sustained Virologic Response 12 Weeks Post-Treatment (SVR12).

2. Clinical Question

The registry record frames the study around both safety and antiviral response in people living with HCV and HIV-1. The primary endpoint was not simply whether HCV RNA fell during treatment: it assessed whether the response was sustained through a defined post-treatment period. The endpoint definition required HCV RNA below the lower limit of quantification 12 weeks after the final dose, with no confirmed quantifiable result before or during that response window.

The study had multiple parts and treatment arms. Regimens differed in whether they included ABT-333 or ribavirin, in treatment duration, and in participants’ HCV genotype, cirrhosis status, prior sofosbuvir experience, and background HIV medicines. These differences matter when interpreting the clinical question: the primary efficacy endpoint applies to a particular genotype 1 analysis group in Part 2, not automatically to every arm or participant described in the registry record.

Although the overall study allocation is recorded as randomized, the stated primary efficacy comparison is with a historical rate. The registry record does not report the primary endpoint result or the lower confidence bound needed to judge it against the non-inferiority threshold. Accordingly, the central question can be described, but the record does not establish whether its stated non-inferiority criterion was met.

3. Trial Design

This was a completed, randomized, open-label, parallel-group study listed as Phase 2 and Phase 3. The registry record reports enrollment of 318. The study began on 2013-08-30, and primary completion was recorded as 2016-07-21. It addressed chronic HCV infection in adults with HIV-1 coinfection, including genotype 1 or 4 infection and participants described as cirrhotic or noncirrhotic.

The study was multipart, with arms that varied by antiviral combination, treatment duration, HCV genotype and cirrhosis status, prior sofosbuvir experience in some groups, and the background HIV regimen. Arms A through D included ABT-450/r/ABT-267 with ABT-333 and ribavirin, with durations of 12 or 24 weeks and differences in the listed background HIV medicines. Other arms included combinations with or without ribavirin, and some included treatment durations of 12 or 24 weeks. These arm descriptions show why a single pooled description should not be taken to mean every participant received the same regimen.

Open-label means the masking field records no masking. In general, when treatment assignment is known, expectations can affect aspects of care or the assessment and reporting of outcomes; an objective laboratory endpoint may be less directly subjective, but open-label status does not remove every possible source of bias. Randomized allocation describes assignment within the study, but the registry record does not provide the allocation sequence details or explain how randomization operated across all parts and arms.

The primary efficacy endpoint was defined for participants in the genotype 1 Analysis Group 1 in Part 2 and compared with a historical SVR12 rate for sofosbuvir plus ribavirin. Thus, the primary question is distinct from a direct randomized comparison between two concurrent treatment groups. The registry record does not report a protocol rationale for the number or composition of arms, the sample-size justification, or details of any interim analyses. Those matters should not be inferred from the study’s phase labels or enrollment figure.

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: In Part 2, participants in Arms E, F, H, I, J all had GT1 infection and received 1 consistent treatment regimen based on label recommendations; they were therefore combined and named the "GT1 Analysis Group."

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: Part 2 randomized or enrolled participants who received at least 1 dose of study drug. Imputation applied; participants with missing HCV RNA data after imputation were counted as failures. The primary efficacy endpoint analysis was based on subjects in the GT 1 Analysis Group in Part 2 containing Arms E, F, H, I, and J.

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.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants in GT1 Analysis Group 1 in Part 2 Achieving 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 in genotype 1 Analysis Group 1 in Part 2 who achieved sustained virologic response 12 weeks after the last actual dose of study drug. SVR12 required plasma HCV RNA below the lower limit of quantification at that follow-up point, without a confirmed quantifiable HCV RNA result before or during the SVR window. The registry record specifies a 95% confidence interval calculated with the Wilson score method for a binomial distribution.

This endpoint captures a response that persists after treatment has ended, rather than only a change observed while participants are taking study drug. In general, a post-treatment endpoint can help distinguish a temporary on-treatment reduction from a response sustained through follow-up. The defined window and the rule about confirmed quantifiable results make the outcome operational: participants are classified according to specified laboratory evidence at a specified time.

The registry record states that the primary efficacy objective was non-inferiority to a historical SVR12 rate for sofosbuvir plus ribavirin. The threshold was that the lower bound of the 95% confidence interval be 74%. In general, a non-inferiority assessment asks whether the data are sufficiently precise to rule out performance below a prespecified margin or threshold; it is not the same question as whether two treatments are identical. The registry record does not report the observed SVR12 percentage or its confidence interval, so the criterion’s result cannot be determined from the available endpoint description.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant is classified according to whether the defined SVR12 criterion was achieved. The reported measure is the percentage of participants meeting that criterion. In general, binary outcomes are often presented as a proportion because the question is whether each person did or did not meet a defined event criterion. The registry record gives no observed percentage for this primary endpoint.

What does the confidence interval add?

The registry record specifies a 95% confidence interval calculated with the Wilson score method for a binomial distribution. In general, a confidence interval gives a range of values compatible with the observed data under the method’s assumptions; it is not a guarantee that the true value lies in that particular interval. The Wilson method is one approach to estimating uncertainty for a binomial proportion. The actual interval limits are not reported in the registry record, so neither its width nor its position relative to the threshold can be assessed.

How does the non-inferiority rule work?

The primary efficacy objective was to compare the percentage achieving SVR12 with a historical rate for sofosbuvir plus ribavirin. The registry record specifies a threshold of 74% for the lower bound of the 95% confidence interval. In general, a non-inferiority rule is designed to assess whether the data are consistent with the studied approach not falling below a prespecified benchmark by more than the permitted amount. That rule relies on the benchmark and analysis being appropriate, as well as on the estimate and its uncertainty. The registry record does not report the endpoint estimate, the confidence limits, or enough detail about the historical benchmark to independently assess those elements.

Non-inferiority is not interchangeable with equivalence or superiority. In general, an equivalence question asks whether differences fall within a prespecified range in both directions, while superiority asks whether evidence supports a result better than a comparator. The registry record describes a non-inferiority objective, not an equivalence or superiority objective. No conclusion about meeting that objective is possible from the endpoint definition alone.

What role does randomization play?

The study is recorded as randomized, open-label, and parallel-group. In general, randomization can help balance measured and unmeasured participant characteristics between concurrent groups, on average, when allocation is properly implemented. Open-label status means masking is recorded as none; knowledge of assigned treatment may influence some care decisions or reporting. These design features do not by themselves establish the result of a particular analysis. The primary efficacy description uses a historical benchmark, and the registry record does not report the details of the randomization process or a concurrent comparator for that primary test.

The multi-arm structure also matters. Regimens varied by use of ABT-333 and ribavirin, treatment duration, genotype, cirrhosis status, sofosbuvir experience in some groups, and background HIV medicines. In general, pooling across groups can make a summary less representative of any one regimen if groups differ in clinically relevant ways. The endpoint description identifies a particular genotype 1 analysis group; it should not be generalized automatically to every arm or to the genotype 4 groups.

How should planning calculations be understood?

The stated sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. In general, such calculations explore how a hypothetical future design might perform under chosen assumptions. They are not observed power, and they do not show the probability that this completed trial’s result is correct. The record does not report the trial’s own sample-size justification, so planning illustrations should not be read as its original design rationale.

In general, power depends on the effect assumed, the outcome variability, the allocation, the analysis method, and the chosen error rate. A calculation based on an observed effect is especially dependent on that effect estimate and can be a poor substitute for a prespecified design calculation. The registry record does not provide enough information to reconstruct a separate sample-size calculation for the primary non-inferiority endpoint.

What can be inferred from the analysis description?

The registry record identifies an intent-to-treat population for Part 2 as randomized or enrolled participants who received at least one dose of study drug. It also states that imputation was applied and that participants with HCV RNA data missing after imputation were counted as failures. In general, counting missing outcome data as failures is a conservative classification for an efficacy response, but its impact depends on how much data are missing and why. The number of missing results and the imputation method are not reported in the registry record.

The record specifies the endpoint definition and confidence-interval method, but does not report a full statistical analysis plan, the analysis result, or details such as covariate adjustment. Those details are not reported in the registry record. Statistical interpretation should therefore stay within the stated endpoint, population, missing-data rule, and historical non-inferiority threshold rather than assuming additional methods.

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("Part 2: GT1 Analysis Group")
n      <- c(200)
events <- c(194)
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  Part 2: GT1 Analysis Group  200  194  97.0  93.6  98.9  93.6  98.6  93.6  98.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures and 3 analyses. It describes a primary endpoint and multiple secondary outcomes, including SVR12 in different parts or arms, on-treatment virologic failure, and relapse12. The record does not report a multiplicity adjustment or a hierarchy governing interpretation across these outcomes. When several outcomes or subgroup analyses are examined, the chance of at least one apparently notable finding can increase if each is treated as a separate test. In general, prespecifying a hierarchy or adjustment can clarify how to interpret multiple tests; whether either was used is not reported in the registry record.

Missing HCV RNA data are addressed in the stated primary population description. Imputation was applied, and participants with HCV RNA data still missing after imputation were counted as failures. This specifies how those remaining missing results were classified for the endpoint, but the imputation method, timing, and number of affected participants are not reported in the registry record. In general, missing-data handling can influence an estimated response percentage, especially when missingness is related to outcome or treatment experience.

The analysis population is described as Part 2 randomized or enrolled participants who received at least one dose of study drug, with the primary efficacy analysis based on the genotype 1 Analysis Group 1. The wording is not enough to establish further population details or to reconstruct the analysis set. The registry record does not report a detailed protocol for handling protocol deviations, additional analysis populations, or sensitivity analyses addressing missing outcomes. These omissions limit independent assessment of the robustness of the primary analysis.

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: colitis (8.3%), dehydration (8.3%), anaemia (5.3%), influenza (5.3%), depression (5.3%).

The serious adverse event figures are reported for selected arms, with the number affected and the number at risk stated for each. For example, the registry record lists 0 of 31 in Part 1a: Arm A, 1 of 12 in Part 1b: Arm D, 6 of 135 in Part 2: Arm I, and 2 of 19 in Part 2: Arm J as having serious adverse events. The other listed groups also have arm-specific counts. These are counts, not evidence that a study drug caused an event.

The registry record lists COLITIS and DEHYDRATION at 8.3% each, and ANAEMIA, INFLUENZA, DEPRESSION, and URETEROLITHIASIS at 5.3% each among the top serious-event terms. It does not report those terms by arm in the information available, so they should not be assigned to a particular group. Death counts are not reported in the registry record.

In general, serious adverse event counts describe observed safety events within the recorded follow-up and analysis definitions; a causal assessment requires more than a count. Differences between arms should not be interpreted as treatment effects without appropriate comparisons, context about follow-up, and information about event ascertainment. The figures also do not replace the efficacy endpoint or resolve the primary non-inferiority question.

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

The record establishes that this completed study was designed to assess safety and efficacy of several ABT-450/r/ABT-267-based regimens, with or without ABT-333 and ribavirin, in adults with HCV and HIV-1 coinfection. It identifies SVR12 in a genotype 1 analysis group in Part 2 as the primary efficacy endpoint and states how that endpoint was defined and analyzed. It also gives a historical non-inferiority threshold and specifies a confidence-interval method.

What the record does not establish is the primary endpoint result. The SVR12 percentage and its 95% confidence interval are not reported in the registry record. Therefore, it is not possible from this information to state whether the lower bound met the 74% threshold, how precise the estimate was, or what the observed efficacy result was. A design objective and a decision rule are not themselves evidence that the objective was met.

In general, evidence against a historical benchmark has a different interpretation from a direct randomized comparison with a concurrent control group. Historical results may differ because of population, setting, follow-up, or outcome assessment. The registry record does not provide the historical rate’s source details or enough information to evaluate comparability. Randomized allocation in the study does not change the fact that the stated primary efficacy objective uses a historical rate.

The reported safety counts indicate that serious adverse events were recorded in some listed arms, while no affected participants are recorded in several others. Those figures should be interpreted as descriptive, arm-specific counts; they do not alone show whether treatment caused an event or establish a comparative safety effect. Death counts are not reported in the registry record. The serious-event terms and their percentages likewise do not identify an arm-specific pattern in the listed information.

These findings cannot be generalized automatically to all people with HCV, all people with HIV, other genotypes, or every regimen. The study population and arms were specific, and the primary endpoint applied to a particular group. The registry record does not report the full primary result, detailed missing-data information, or a multiplicity plan. The most defensible interpretation is therefore about the study’s design, endpoint, analysis rule, and recorded safety counts—not about an unreported efficacy conclusion or treatment recommendation.

14. Why This Trial Matters Statistically

This trial raises several statistical issues that are important when reading clinical research in a population with coexisting infections. Its primary endpoint was a post-treatment virologic response, while the study’s stated purpose also included assessing safety. Separating those questions prevents safety counts from being mistaken for evidence about efficacy, or an efficacy objective from being treated as a safety conclusion.

The primary analysis used a non-inferiority framework against a historical rate. In general, that design makes the confidence interval and prespecified threshold essential: the point estimate alone does not answer whether the stated criterion was met. Here, the lower confidence-bound threshold was 74%, but the registry record does not report the lower bound or the SVR12 estimate. This is a useful reminder that a clearly described hypothesis is not a reported result.

The trial’s randomized, open-label, parallel structure coexists with a multipart set of arms and an efficacy comparison to historical data. These design elements answer different questions. Randomization may support comparisons among concurrently assigned groups, while a historical benchmark requires attention to comparability across studies. The registry record does not report enough detail to assess the source and suitability of that benchmark.

Multiple arms and outcomes also make interpretation dependent on population definitions and any multiplicity plan. The record lists several secondary outcome types, while the main endpoint targets a particular genotype 1 analysis group. This illustrates why conclusions should remain tied to the analysis population and endpoint actually specified, rather than being broadened to all study participants or every regimen.

Finally, the missing-data rule is explicit at a high level: residual missing HCV RNA after imputation counted as failure. But the imputation method and amount of missing data are not reported. Statistical transparency requires both the rule and enough detail to evaluate how it affected the result. In this case, the rule can be described, but its quantitative impact cannot be assessed from the registry record.

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 primary efficacy result is not reported in the registry record: neither the SVR12 percentage nor its 95% confidence interval is available in the endpoint information. As a result, the stated non-inferiority decision rule cannot be checked. The historical benchmark is described as a rate for sofosbuvir plus ribavirin, but source details and evidence that the historical population is comparable are not reported.

The study included multiple arms with differences in regimen, duration, HCV genotype, cirrhosis status, prior sofosbuvir experience in some groups, and background HIV medicines. These features make broad pooling or generalization difficult without arm-specific results and clear analysis populations. The registry record does not provide the complete endpoint results for each arm in the information available.

The open-label design means masking is recorded as none. In general, lack of masking can affect subjective assessments or behavior, although the primary endpoint is based on HCV RNA. The record does not report details of outcome assessment beyond the endpoint definition. The randomization process and its implementation across the multipart study are also not described in detail.

For missing outcomes, the record states that imputation was applied and remaining missing HCV RNA results counted as failures. The imputation method, extent of missingness, and sensitivity analyses are not reported. The record also does not report a multiplicity strategy, a full analysis plan, or the study’s sample-size justification. Those gaps limit independent assessment of analysis robustness and the basis for the design. Safety counts are available for selected groups, but death counts are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Multipart, Open-label Study to Evaluate the Safety and Efficacy of ABT-450/r/ABT-267 With and Without ABT-333 Coadministered With and Without Ribavirin in Adult With Genotype 1 or 4 Hepatitis C Virus (HCV) Infection and Human Immunodeficiency Virus, Type 1 Coinfection — NCT01939197.
• Registry record last updated 2021-07-12; status last verified 2021-07.
• Results first posted 2017-11-17.
• 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.

19. Record Summary

The registry record describes a completed, randomized, open-label, parallel study listed as Phase 2 and Phase 3, with enrollment of 318. It investigated ABT-450/r/ABT-267 regimens with or without ABT-333 and ribavirin in adults with genotype 1 or 4 chronic HCV and HIV-1 coinfection. Arms differed in treatment duration and participant or background-treatment characteristics.

The primary endpoint was SVR12 in genotype 1 Analysis Group 1 in Part 2, defined using HCV RNA below the lower limit of quantification 12 weeks after the last actual dose and no confirmed quantifiable result within the specified window. The registry record states a Wilson score 95% confidence interval and a historical non-inferiority threshold of 74% for the lower bound.

The primary efficacy percentage and interval are not reported in the registry record, so whether the non-inferiority criterion was met cannot be determined from this information. The record also describes imputation with remaining missing HCV RNA results counted as failures, and lists serious adverse event counts for selected arms. Death counts are not reported.