Efficacy and Safety of Glecaprevir (ABT-493)/Pibrentasvir (ABT 530) (GLE/PIB) in Combination With Sofosbuvir and Ribavirin in Participants With Hepatitis C Virus Who Did Not Respond to Treatment in a Previous AbbVie Clinical Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Glecaprevir (ABT-493)/Pibrentasvir (ABT 530) (GLE/PIB) in Combination With Sofosbuvir and Ribavirin in Participants With Hepatitis C Virus Who Did Not Respond to Treatment in a Previous AbbVie Clinical Study (NCT02939989), a non-randomized 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

MAGELLAN-3 was an open-label, multicenter Phase 3 study with non-randomized allocation and a parallel-group structure. It was designed to evaluate the efficacy and safety of glecaprevir/pibrentasvir in combination with sofosbuvir and ribavirin among participants with hepatitis C who had experienced virologic failure in an AbbVie parent study. The registry lists an enrollment of 33 and a completed study status.

The two treatment groups received the same combination medicines but had different treatment durations. Participants without cirrhosis who had non-genotype 3 infection and were naïve to protease inhibitor and/or NS5A inhibitor treatment before participation in the parent study were assigned to the 12-week regimen. The 16-week group included participants with genotype 3, compensated cirrhosis, and/or prior protease inhibitor or NS5A inhibitor experience in the parent study. These are different participant profiles, not groups formed by random assignment.

The registry lists the study start as 2016-11-21 and primary completion as 2021-05-07. Open-label means masking was absent; the registry lists no masking. The record does not report the rationale for choosing these durations, a sample-size justification, or further details of allocation procedures. Because treatment duration and eligibility characteristics differed together, outcomes across the groups would not by themselves isolate the effect of duration.

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: Participants were allocated to 1 of 2 treatment arms based on HCV GT, cirrhosis status, and treatment experience with protease inhibitor (PI) and/or nonstructural viral protein 5A protease inhibitor (NS5Ai)-containing regimens prior to enrolling in the AbbVie HCV Parent Study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT) population, which included all participants who received at least 1 dose of study drug. A backward imputation method was used to impute missing responses. Participants with missing data after backward imputation were counted as non-responders.

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: The intention-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug.

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, Week 24 or Week 28 depending on the treatment regimen..

The primary endpoint was the percentage of participants with sustained virologic response 12 weeks after the last actual dose of study drug. The registry defines response as plasma hepatitis C virus RNA below the lower limit of quantification, specified as 15 IU/mL, at that follow-up time. The assessment was at Week 24 or Week 28, depending on treatment regimen.

In general, sustained virologic response is used as a virologic endpoint because it records whether viral RNA is below the specified measurement threshold at a defined time after treatment ends. It is a binary outcome for each participant: the endpoint classifies a participant as a responder or non-responder under the stated definition. The percentage summarizes the proportion classified as responders in the analysis population.

The endpoint definition is not itself an outcome. Although the registry identifies a 95% confidence interval as the dispersion measure, it does not report an endpoint estimate or interval in the record. The number of participants who met the response definition is therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a binary participant-level outcome. Each participant is classified according to whether HCV RNA is below the stated lower limit of quantification at the specified follow-up. The group percentage is a summary of those classifications. In general, a percentage gives an easily interpreted account of how common the outcome was in the analyzed population, but it does not describe the precision of that estimate by itself.

The registry specifies a 95% confidence interval for the primary endpoint. In general, a confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies in the interval, and it does not address every possible source of bias. Here, the registry record gives the interval type but not the endpoint estimate or interval limits. The precision of the primary result therefore cannot be evaluated from the record.

The analysis population was intention-to-treat, defined in the registry as all participants who received at least 1 dose of study drug. In general, an intention-to-treat approach aims to retain participants in the analysis population defined for the study rather than limiting the analysis only to those who completed treatment or follow-up. The precise implications depend on the trial’s allocation and analysis procedures. Because this study was non-randomized, the label does not create the balance that random allocation can provide.

Missing responses were handled using backward imputation. The registry says that participants still missing data after backward imputation were counted as non-responders. In general, imputation assigns an analysis value when an outcome is not observed, while a non-responder rule treats unresolved missing outcomes as failures to meet the endpoint. Such rules can affect an estimated response percentage. The record does not report how many observations required imputation, how many remained missing, or whether other missing-data analyses were conducted.

The study used parallel groups, but allocation was non-randomized. General statistical interpretation distinguishes a treatment comparison from an association between treatment groups: randomization can help balance known and unknown prognostic characteristics, whereas assignment based on eligibility characteristics can leave groups systematically different. In MAGELLAN-3, the groups differed in the characteristics used to determine regimen duration. Any comparison between them would therefore need cautious interpretation, and the registry record does not list adjusted analyses that might address measured differences.

The registry lists no analyses for the outcome measures. It also does not report a statistical analysis plan, prespecified modeling choices, covariate adjustments, or a rationale for the sample size. These details are not reported in the registry record. The 95% confidence interval designation alone does not reveal the method used to calculate it.

General statistical concepts can also matter for event outcomes. For example, confidence intervals for binary outcomes depend on the number of participants and observed events, and estimates can be unstable when information is limited. No such calculations can be reconstructed for the primary endpoint because its response counts are not reported. The safety counts describe event categories but do not provide inferential comparisons between regimens.

The record lists two secondary outcomes: on-treatment virologic failure and post-treatment relapse. It does not give their results or the method used to analyze them. When several outcomes are tested, multiplicity can increase the chance of at least one apparently unusual result; statistical plans may address this issue by specifying which outcomes are primary and how secondary tests are interpreted. The registry record does not report a multiplicity adjustment or related testing strategy. No conclusion about such a strategy can be drawn from the listed outcome names alone.

Finally, statistical significance and clinical importance are different concepts in general. A p-value, if reported, would address compatibility with a specified statistical model and null hypothesis; it would not establish the size, precision, or practical meaning of an effect by itself. No p-value or primary endpoint estimate is reported in the registry record, so these aspects cannot be evaluated for this study.

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("Glecaprevir/Pibrentasvir + SOF + RBV for 12 Weeks", "Glecaprevir/Pibrentasvir + SOF + RBV for 16 Weeks")
n      <- c(5, 28)
events <- c(5, 27)
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  Glecaprevir/Pibrentasvir + SOF + RBV for 12 Weeks  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  Glecaprevir/Pibrentasvir + SOF + RBV for 16 Weeks  28  27  96.4  81.7  99.9  82.3  99.4  82.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint was SVR12. The registry also lists two secondary outcomes: percentage of participants with on-treatment virologic failure and percentage with post-treatment relapse. Their results are not reported in the registry record. The record does not state whether secondary outcome testing was adjusted for multiplicity, whether an ordered testing procedure was planned, or how findings across outcomes were to be interpreted. Those statistical-plan details are not reported in the registry record.

The registry defines the primary population as intention-to-treat participants who received at least 1 dose. It specifies backward imputation for missing responses and says that participants still missing after imputation were counted as non-responders. This rule makes the endpoint classification explicit for unresolved missing data. However, the number of participants with missing measurements, the number imputed, and the number remaining missing are not reported in the registry record. It is therefore not possible to assess how much the imputation rule influenced the endpoint estimate.

The registry lists no outcome analyses. It does not report an analysis plan, sensitivity analyses for missing data, subgroup analyses, or adjusted comparisons. The sample-size justification and any interim-analysis plan are also not reported in the registry record. The absence of these details should not be interpreted as evidence that a particular analysis was or was not conducted outside the registry entry; it means those details cannot be established from the record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chronic gastritis (20.0%), pneumonia bacterial (20.0%), bronchiectasis (20.0%), chronic obstructive pulmonary disease (20.0%), cholelithiasis (3.6%).

The registry reports serious adverse events in both treatment groups and in total. In the 12-week group, 5 participants were at risk and 1 was affected; in the 16-week group, 28 were at risk and 2 were affected. Overall, 33 participants were at risk and 3 were affected. No deaths were reported.

For other adverse events, the registry reports 5 participants at risk and 5 affected in the 12-week group, and 28 at risk and 21 affected in the 16-week group. Overall, 33 were at risk and 26 were affected. These are counts of participants, not a comparison adjusted for the different group profiles. The registry does not establish that reported events were caused by study treatment.

The listed serious-event terms include chronic gastritis, pneumonia bacterial, bronchiectasis, and chronic obstructive pulmonary disease, each reported as 20.0%. Cholelithiasis and hepatic function abnormal are each listed as 3.6%. The record does not explain the denominator for these term percentages in the material described, so they should be read as registry-reported percentages rather than recalculated proportions. The small enrollment and non-randomized group assignment limit comparative safety interpretation.

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

This registry record describes a Phase 3 study of glecaprevir/pibrentasvir with sofosbuvir and ribavirin among participants with hepatitis C who had experienced virologic failure in an AbbVie parent study. It specifies the primary endpoint as SVR12 and gives the threshold and follow-up timing used to define response. It also records serious and other adverse event counts.

However, the record does not report the primary endpoint result. It therefore does not show how many participants achieved SVR12, what percentage did so, or how precisely that percentage was estimated. It also does not report results for the listed secondary virologic outcomes. Completion status does not substitute for those outcome data.

The two treatment groups are not a randomized comparison. They received different treatment durations and were distinguished by participant characteristics and prior treatment experience. Differences between their outcomes, if available, could reflect those differences as well as treatment duration. The registry record does not give adjusted analyses that would allow those factors to be separated.

The safety data indicate the number of participants affected in the categories reported, but they do not establish causation or permit a reliable treatment comparison. The event counts should be interpreted alongside the small enrollment and the differing group profiles. Overall, the record supports a description of the study question, design, endpoint definition, missing-data rule, and selected safety counts. It does not provide enough outcome information to quantify the primary response or draw a comparative efficacy conclusion.

14. Why This Trial Matters Statistically

MAGELLAN-3 is statistically notable because it addresses a treatment question in participants who had already experienced virologic failure in an AbbVie HCV study. The registry describes a combination regimen and a primary endpoint tied to a defined post-treatment assessment. That context makes clear which population and outcome the study was intended to examine, without implying an outcome that is absent from the record.

Its design also illustrates why study groups should not automatically be treated as exchangeable. The 12-week and 16-week regimens were assigned to different participant profiles rather than by randomization. In general, treatment groups that differ at baseline can also differ in prognosis, so an observed contrast does not isolate a treatment-duration effect without additional assumptions and appropriate analysis. The registry record does not list adjusted comparisons.

The stated intention-to-treat population and missing-response rule are important for interpreting an endpoint percentage. Counting unresolved missing responses as non-responders can affect the estimate, while the lack of reported missing-data counts prevents readers from assessing the scale of that influence. The record’s specification of a 95% confidence interval is useful for identifying the intended precision measure, but the absent endpoint estimate and interval prevent assessment of uncertainty.

These features make the registry entry useful for understanding the planned question and limitations of the available reporting, while also showing why design details and outcome results must be read together. The primary endpoint and secondary outcomes are named, but their results are not reported in 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 main limitation for interpreting efficacy is that the registry record does not report the primary SVR12 result, its confidence interval, or the results of the listed secondary outcomes. No effect estimate, uncertainty estimate, or analysis output is available in the record described. Consequently, efficacy cannot be quantified from this information.

The non-randomized allocation limits comparisons between the treatment groups. Regimen duration was tied to genotype, cirrhosis status, and prior protease inhibitor and/or NS5A inhibitor experience. Those group differences complicate any attempt to attribute a between-group contrast to duration alone. The registry record does not report adjusted estimates or other analyses addressing these differences.

Enrollment was 33, and the safety data list 5 participants in the 12-week group and 28 in the 16-week group. The record does not provide primary endpoint counts or missing-data counts, so the precision of efficacy estimates and the impact of the specified imputation rule cannot be assessed. It also does not report the sample-size justification, interim-analysis plan, or detailed statistical analysis plan.

Safety reporting is limited to the listed participant counts and event terms. The registry does not establish treatment causality, and the treatment groups are not suitable for an unadjusted like-for-like safety comparison. These limitations concern what can be concluded from the registry record; they do not establish what analyses or information may exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of Glecaprevir (ABT-493)/Pibrentasvir (ABT 530) (GLE/PIB) in Combination With Sofosbuvir and Ribavirin in Participants With Hepatitis C Virus Who Did Not Respond to Treatment in a Previous AbbVie Clinical Study — NCT02939989.
• Registry record last updated 2022-05-04; status last verified 2022-04.
• Results first posted 2022-05-04.
• 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

NCT02939989, MAGELLAN-3, was an open-label, multicenter, non-randomized Phase 3 study of glecaprevir/pibrentasvir with sofosbuvir and ribavirin. It enrolled 33 participants with hepatitis C who had experienced virologic failure in an AbbVie parent study. Treatment duration was 12 or 16 weeks according to participant characteristics and treatment history.

The primary endpoint was SVR12, defined by HCV RNA below 15 IU/mL at the specified post-treatment assessment. The registry describes an intention-to-treat population and a rule counting unresolved missing responses as non-responders. It reports selected adverse-event counts and no deaths, but does not report the primary endpoint result, secondary outcome results, or outcome analyses. The study status is completed.