A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir Co-administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (AGATE-1): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir Co-administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (AGATE-1) (NCT02265237), a randomized phase 3 study. The primary outcome is Percentage of Participants in Arms A, B and C With Sustained Virologic Response 12 Weeks Post-treatment (SVR12).

2. Clinical Question

3. Trial Design

The registry record describes a completed, phase 3, randomized, open-label, parallel-group study with enrollment of 184. Participants were assigned to treatment groups, but masking was not used. The study start date was 2014-10-28, and primary completion was 2016-07-28.

All four arms used ombitasvir/paritaprevir/ritonavir at 25/150/100 mg with ribavirin. Arms A and B received 12 and 16 weeks of treatment, respectively, for genotype 4 participants who were treatment-naïve or had prior interferon/ribavirin treatment. Arm C received 24 weeks for those same treatment-history categories. Arm D received 24 weeks and was for participants previously treated with sofosbuvir/pegylated interferon/ribavirin or sofosbuvir/ribavirin.

The primary outcome is reported for Arms A, B, and C. Its analysis population is described as intent-to-treat, defined in the record as participants who received at least one dose. Arm D has a small safety population reported, but its primary SVR12 result is not reported in the registry record. The record does not report the randomization ratio, allocation concealment procedures, stratification factors, or a detailed protocol for how treatment duration was assigned among eligible participants.

Because the study was open-label and did not include a placebo or untreated arm in the posted primary outcome, its main outcome describes response proportions across the assigned regimen-duration groups. The design supports examining those groups as randomized, but does not by itself make the findings a comparison against other therapies or populations.

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 analysis population: all participants who received at least 1 dose of study drug. One participant randomized to the arm B (16 weeks arm) was erroneously administered study drug for 12 weeks (as in arm A). Therefore this participant is included in arm A for the safety population.

As Enrolled (Overall Study)

As Treated (Overall Study)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) 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: Safety analysis population: all participants who received at least 1 dose of study drug. One participant randomized to arm B (16 weeks arm) was erroneously administered study drug for 12 weeks (as in arm A). Therefore this participant is included in arm A for the safety population.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants in Arms A, B and C With Sustained Virologic Response 12 Weeks Post-treatment (SVR12), measured over 12 weeks after the last actual dose of study drug.

The primary endpoint is the percentage of participants with sustained virologic response 12 weeks after treatment, called SVR12. The registry defines a response as plasma HCV RNA below the lower limit of quantification 12 weeks after the last dose of study drug. The timeframe is tied to each participant’s last actual dose, rather than simply to a fixed calendar date from enrollment.

SVR12 is used as a virologic outcome because it records whether viral RNA is quantifiable after treatment has ended and a follow-up period has passed. This makes it distinct from an on-treatment measure: the endpoint assesses response after the treatment course, not only while participants are receiving study drugs. That distinction is also reflected in the secondary outcomes, which separately list on-treatment virologic failure and post-treatment relapse.

The endpoint is reported as a percentage, with a 97.5% confidence interval for each primary arm. The analysis population is described as all participants who received at least one dose. Participants with missing data after backwards imputation were treated as nonresponders, according to the registry description. This rule affects how incomplete outcome information contributes to the reported response percentage.

The brief summary says the study aimed to compare response with a clinically relevant threshold based on SVR rates for genotype 4 participants treated with pegylated interferon and ribavirin. The numerical threshold and the statistical procedure for that threshold comparison are not reported in the registry record.

7. Results Posted in the Registry

• Arm B: 100.0% (61/61) versus 96.6% (57/59) on control; risk difference 3.4 percentage points (95% CI -1.2 to 8.0), risk ratio 1.04 (0.99–1.09); unadjusted two-proportion z-test p = 0.147.
• Arm C: 93.4% (57/61) versus 96.6% (57/59) on control; risk difference -3.2 percentage points (95% CI -10.9 to 4.6), risk ratio 0.97 (0.89–1.05); unadjusted two-proportion z-test p = 0.426.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Percentage of Participants With SVR12 in Participants Receiving 12 Weeks (Arm A) of Treatment Compared to Participants Receiving 16 Weeks of Treatment (Arm B)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Arm B: 100.0% (61/61) versus 96.6% (57/59) on control; risk difference 3.4 percentage points (95% CI -1.2 to 8.0), risk ratio 1.04 (0.99–1.09); unadjusted two-proportion z-test p = 0.147.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm B and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With SVR12 in Participants Receiving 16 Weeks (Arm B) of Treatment Compared to Participants Receiving 24 Weeks of Treatment (Arm C)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Arm C: 93.0% (53/57) versus 100.0% (61/61) on control; risk difference -7.0 percentage points (95% CI -13.6 to -0.4), risk ratio 0.93 (0.87–1.00); unadjusted two-proportion z-test p = 0.035.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Arm C than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants in Arms A, B and C With On-treatment Virologic Failure

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Arm B: 0.0% (0/61) versus 1.7% (1/59) on control; risk difference -1.7 percentage points (95% CI -5.0 to 1.6); unadjusted two-proportion z-test p = 0.307.
  • Arm C: 0.0% (0/61) versus 1.7% (1/59) on control; risk difference -1.7 percentage points (95% CI -5.0 to 1.6); unadjusted two-proportion z-test p = 0.307.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm B and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Arm C and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the primary response assessment in two ways: they compare response across treatment durations and describe virologic failure during treatment and relapse after treatment. Together, these outcomes provide additional views of the study’s response pattern, but they do not change the primary endpoint’s definition or analysis population. The posted outcomes cover Arms A, B, and C; the primary results do not include Arm D.

The registry reports sponsor analyses for the two duration comparisons using Mantel-Haenszel stratum-adjusted differences. It also permits simple unadjusted recalculations from posted counts. Those approaches are not equivalent, and the registry record does not report the strata or enough detail to reproduce the adjusted method. Any apparent difference between the adjusted and unadjusted numerical results should be considered in light of that methodological distinction, rather than treated automatically as a data error.

The virologic failure outcome is reported for treatment through Week 24 or premature treatment discontinuation. The posted pattern is sparse, including arms with no reported failures, so estimates based on few events are inherently imprecise. The registry also lists post-treatment relapse as a secondary outcome, but numerical results for that outcome are not reported in the registry record.

Secondary results generally carry less weight than the primary result when the registry record does not report a multiplicity strategy. If several outcomes or pairwise comparisons are tested, the chance of at least one apparently notable result can increase. The record does not say whether the secondary comparisons were confirmatory, whether their tests were adjusted for multiple testing, or how their order was set. For that reason, secondary findings are best viewed as supportive or exploratory descriptions unless a fuller analysis plan establishes otherwise. They add context, but should not be used to overrule the primary estimates or to imply a broader conclusion than the posted data support.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Percentage of Participants With SVR12 in Participants Receiving 12 Weeks (Arm A) of Treatment Compared to Participants Receiving 16 Weeks of Treatment (Arm B)
• Percentage of Participants With SVR12 in Participants Receiving 16 Weeks (Arm B) of Treatment Compared to Participants Receiving 24 Weeks of Treatment (Arm C)
• Percentage of Participants in Arms A, B and C With On-treatment Virologic Failure
• Percentage of Participants in Arms A, B and C With Post-treatment Relapse

9. Statistical Interpretation

10. Statistical Methods Explained

What the percentages represent

For a binary endpoint, each participant is classified as having or not having the defined outcome. The reported percentage is the proportion classified as having SVR12 in the relevant arm. In this study, the registry states that participants with missing data after backwards imputation were counted as nonresponders. The percentages therefore reflect the stated missing-data rule as well as observed outcome status.

The primary estimates are 96.6%, 100.0%, and 93.4% for Arms A, B, and C. Their respective 97.5% confidence intervals are 86.7% to 99.2%, 92.4% to 100.0%, and 82.6% to 97.7%. A confidence interval describes uncertainty around an estimated response proportion under the assumptions of the method used. It is not a range containing a known fixed percentage with certainty, and it does not account for every possible source of bias or uncertainty.

How to interpret the recalculated comparisons

The posted recalculations compare observed proportions as unadjusted risk differences. A risk difference is the response proportion in one arm minus the response proportion in the reference arm, expressed on the proportion scale. The estimates and interval endpoints from these recalculations are not repeated because they are more precise than three decimal places. The associated unadjusted p-values are 0.147 for Arm B versus Arm A and 0.426 for Arm C versus Arm A.

In general, a p-value describes how unusual data at least as discordant with a specified null hypothesis would be if that null hypothesis and the analysis assumptions held. It is not the probability that the null hypothesis is true, nor a measure of the size or clinical importance of a difference. These recalculated p-values do not substitute for the sponsor’s analyses or for an analysis plan that is not reported in the registry record.

Why the reported analysis and a simple recalculation can differ

A simple recalculation from arm-level counts does not necessarily reproduce an analysis that adjusts for strata or other design features. The sponsor reports Mantel-Haenszel analyses for two secondary duration comparisons; those are stratum-adjusted estimates. The registry does not report the strata used or enough detail to recreate those calculations. The secondary results should therefore be interpreted according to the analysis actually reported for each comparison, with unadjusted recalculations treated as a separate, simpler analysis.

For binary outcomes with small numbers of events or response proportions close to 100%, estimates can be sensitive to the method used. General statistical methods may use different approximations or adjustments, and the resulting interval or test can vary. The exact method for the primary arm confidence intervals is not specified in the registry record.

Planning illustrations are not trial power

The registry’s planning illustrations are explicitly based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. For planning around 100% of the observed effect, the listed requirements are 739 participants per arm for 80% power and 988 participants per arm for 90% power. For 75% of the observed effect, the corresponding figures are 1,214 and 1,625. For 50% of the observed effect, they are 2,507 and 3,355.

These are hypothetical planning calculations, not observed power and not the sample-size basis for this trial. The registry record does not report the trial’s own sample-size justification or the effect and assumptions used when the study was designed. In general, planning estimates depend on the chosen effect, error rate, allocation, outcome model, and analysis method; changing those assumptions changes the required sample size.

11. Confidence Intervals and Precision

The primary arm percentages are accompanied by 97.5% confidence intervals. Arm A’s interval is 86.7% to 99.2%, Arm B’s is 92.4% to 100.0%, and Arm C’s is 82.6% to 97.7%. Each interval spans a range of response proportions compatible with the estimate under the interval method’s assumptions. The ranges are not narrow enough to treat the reported percentages as exact population values.

Arm B’s observed percentage is at the upper boundary of the scale, and its confidence interval also reaches 100.0%. This boundary does not imply that the true response proportion is known to be 100.0%. Likewise, the lower and upper limits for Arm A and Arm C show that their underlying proportions could plausibly differ from their observed estimates. General statistical intervals for proportions become especially important to interpret cautiously near zero or 100%, where the scale has a boundary.

Arm-level sample sizes were 59 for Arm A, 61 for Arm B, and 61 for Arm C. Confidence interval width reflects both the observed outcome and the amount of information in the arm; relatively small samples leave uncertainty even when observed response percentages are high. The intervals are for individual arms and should not be used as a replacement for a direct interval on a between-arm contrast.

The simple recalculated comparisons have uncertainty as well. Their unadjusted p-values are 0.147 for Arm B versus Arm A and 0.426 for Arm C versus Arm A. Neither p-value gives the magnitude or precision of a contrast by itself. The precise interval endpoints for those recalculations are not included in this explanation because they exceed the three-decimal reporting limit. The registry’s sponsor-reported secondary comparisons use a different, stratum-adjusted method and have their own confidence intervals.

12. Analyses Reported by the Sponsor

The sponsor’s primary reported analyses give the same arm-specific SVR12 percentages as the posted primary outcome: 96.6% for Arm A, 100% for Arm B, and 93.4% for Arm C. The sponsor reports 97.5% confidence intervals of 86.7% to 99.2%, 92.4% to 100.0%, and 82.6% to 97.7%, respectively. No p-values are reported alongside those primary arm estimates.

The unadjusted recalculations compare arm-level response proportions directly. For the secondary duration comparisons, the sponsor instead reports Mantel-Haenszel stratum-adjusted differences, with 95% confidence intervals and p-values. These estimates use a different analysis approach, so their numerical values and signs should not be treated as interchangeable with an unadjusted risk difference. The registry record does not identify the adjustment strata or provide the detail needed to reconstruct the sponsor’s calculations.

The record does not flag a discrepancy between the posted and recalculated results. The sponsor’s reported analysis remains the relevant result for its stated stratified method; the simpler recalculations are supplementary descriptions, not replacements for that analysis.

13. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary endpoint and several secondary outcomes, including two duration comparisons, on-treatment virologic failure, and post-treatment relapse. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy controlling the overall type I error across the set of analyses. Consequently, the unadjusted secondary p-values should not be interpreted as if they were necessarily protected against the increased false-positive risk that can arise from multiple testing. Whether a multiplicity procedure was used is not reported in the registry record.

The primary endpoint population is defined as all participants who received at least one dose of study drug. The registry says missing data after backwards imputation were counted as nonresponders. This makes the missing-data handling explicit at a high level, but the detailed imputation procedure, timing rules, and amount of missing outcome data are not reported in the registry record. The potential sensitivity of the result to other missing-data assumptions is therefore not available from these registry entries.

The sponsor’s primary arm estimates are reported without a p-value. The brief summary describes comparison with a clinically relevant threshold based on SVR rates for genotype 4 participants treated with pegylated interferon and ribavirin, but the numerical threshold and its inferential procedure are not reported in the registry record. The record also does not report whether interim analyses occurred, how any interim testing was handled, or the trial’s own sample-size justification.

Randomization is stated, but the allocation ratio, concealment procedures, randomization strata, and details of the planned statistical model are not reported in the registry record. These omissions limit independent reconstruction of the analyses. They also make it important to distinguish the stated analysis population and sponsor-reported methods from supplementary unadjusted calculations based only on the posted arm-level summaries.

14. 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: anaemia (3.3%), acute coronary syndrome (3.3%), intervertebral disc protrusion (3.3%), haemorrhagic anaemia (1.7%), oesophageal varices haemorrhage (1.7%).

The safety summary reports serious adverse events for Arms A through D. Serious adverse events were reported for 4 of 60 participants at risk in Arm A, 4 of 60 in Arm B, 3 of 61 in Arm C, and 0 of 3 in Arm D. These counts describe the posted safety data; they are not a causal comparison and do not establish that one duration is safer than another. Arm D’s safety group is particularly small, so its count should not be read as a stable estimate of risk.

The registry lists anaemia, acute coronary syndrome, and intervertebral disc protrusion at 3.3% each among the leading serious-event terms. Haemorrhagic anaemia, oesophageal varices haemorrhage, and portal vein thrombosis are each listed at 1.7%. The listed terms are descriptions of reported events, not an exhaustive account of all safety outcomes. The numbers of deaths are not reported in the registry record.

Other adverse events are reported for 46 of 60 participants in Arm A, 55 of 60 in Arm B, 50 of 61 in Arm C, and 3 of 3 in Arm D. The record’s summary does not provide enough detail to assess event severity beyond the serious-event designation, duration, relatedness, or comparative uncertainty. The open-label design and group-size differences are also relevant when interpreting descriptive safety counts.

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

The posted primary results establish what was observed in the study’s stated analysis population: high SVR12 percentages in each of Arms A, B, and C, with the highest observed percentage in Arm B. Their confidence intervals indicate uncertainty around each arm’s response proportion. The data do not establish that any arm’s underlying response is exactly equal to its observed percentage.

The results do not by themselves establish that a longer or shorter duration is superior. The registry includes duration comparisons, but their interpretation depends on the analysis method, uncertainty, and whether multiplicity was addressed. The simple recalculated p-values are unadjusted, while the sponsor reports stratum-adjusted analyses for secondary duration comparisons. The registry record does not provide the full analysis plan needed to determine how all comparisons were intended to fit together.

The study does not provide a concurrent comparison with placebo, no treatment, or pegylated interferon/ribavirin in the posted primary results. Although the brief summary refers to a threshold based on prior pegylated interferon/ribavirin SVR rates, the threshold and its test are not reported in the registry record. Therefore, the posted results should not be presented as a randomized comparison against that historical regimen.

These findings are specific to the enrolled population, treatment histories, regimens, and follow-up definition recorded for this trial. Arm D’s primary SVR12 outcome is not reported in the registry record, so the primary response estimates cannot be extended to that group from these results. The results also do not answer questions about outcomes beyond the stated follow-up window or about other populations not represented in the record.

In general, a trial outcome is one source of evidence, not a personalized prediction. The statistical interpretation concerns observed proportions and their uncertainty; it is not medical advice or a treatment recommendation.

16. Why This Trial Matters Statistically

This trial is statistically useful as an example of why a high observed response percentage should be read alongside its confidence interval, analysis population, and endpoint definition. Arm B’s observed SVR12 percentage is 100.0%, but the reported interval extends down to 92.4%. That interval makes clear that an observed proportion at the scale’s upper boundary is not the same as certainty about the population response proportion.

The study also illustrates the distinction between an arm-specific estimate and a between-arm comparison. Separate percentages describe each group; a direct contrast addresses a different question and has its own uncertainty. Recalculations from arm-level summaries are not interchangeable with the sponsor’s stratum-adjusted secondary analyses, particularly when the adjustment details are not reported.

Another statistical lesson is that the treatment-duration groups are not the only relevant context. The trial enrolled participants with different prior treatment histories, and Arm D had a different eligibility history from Arms A, B, and C. The primary outcome is reported only for Arms A, B, and C. Thus, interpretation requires attention to which group a result describes and whether that group is represented in the outcome analysis.

Finally, the registry record shows why transparency about missing data, multiplicity, sample-size rationale, and analysis methods matters. Some outcome definitions and missing-data handling are stated, while important details of the statistical plan are not reported in the registry record. A statistically careful reading can describe the posted response pattern while keeping those limitations visible.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several trial-specific limitations constrain interpretation. The study was open-label, and the registry states that masking was not used. The primary outcome is a laboratory-defined virologic response, but the registry record does not describe blinded endpoint assessment. The primary result is also limited to Arms A, B, and C; an SVR12 result for Arm D is not reported in the registry record, despite its inclusion in the arm descriptions.

The treatment groups differ by planned duration, while eligibility also depends on treatment history. Arm D specifically represents participants previously treated with sofosbuvir-based regimens, unlike the treatment-history descriptions for Arms A, B, and C. The record does not report randomization strata or enough detail to assess how prior treatment history was handled in analyses. Generalization across these groups should therefore be cautious.

The registry describes a clinically relevant threshold based on prior pegylated interferon/ribavirin SVR rates, but its numerical value and statistical test are not reported in the registry record. It also does not report the trial’s sample-size justification, interim analyses, full missing-data details, or a multiplicity strategy. These omissions prevent a complete audit of the original inferential plan.

The numerical outcome data are based on relatively modest arm sizes, and the confidence intervals remain broad enough to leave meaningful uncertainty about response proportions. Some secondary outcomes involve sparse events, making their estimates particularly sensitive to small changes in counts. The post-treatment relapse outcome is named but its numerical results are not reported in the registry record. Safety summaries are descriptive, and deaths are not reported in the registry record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-450/Ritonavir Co-administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (AGATE-1) — NCT02265237.
• Registry record last updated 2017-08-31; status last verified 2017-08.
• Results first posted 2017-08-31.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

This completed phase 3 randomized, open-label, parallel-group study enrolled 184 adults with genotype 4 chronic hepatitis C and cirrhosis. Arms A, B, and C received ombitasvir/paritaprevir/ritonavir with ribavirin for 12, 16, and 24 weeks, respectively. Arm D received 24 weeks and had a distinct prior-treatment eligibility description.

The primary endpoint was SVR12, defined as HCV RNA below the lower limit of quantification 12 weeks after the last dose. The reported percentages were 96.6% in Arm A, 100.0% in Arm B, and 93.4% in Arm C, with 97.5% confidence intervals. Missing participants after backwards imputation were counted as nonresponders.

The registry reports secondary duration comparisons and safety summaries, but does not report the full statistical plan, multiplicity strategy, or numerical primary threshold comparison. The findings describe the posted outcomes and their uncertainty; they do not establish comparisons with an unstudied concurrent treatment group.