Study of A Combination Pill With GS-7977 and GS-5885 for Hepatitis C in People With HIV: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of A Combination Pill With GS-7977 and GS-5885 for Hepatitis C in People With HIV (NCT01878799), a na phase 2 study. The primary outcome is Percentage of Participants With Achieved SVR12 (HCV RNA <LLOQ 12 Weeks After Completion of Treatment).

2. Clinical Question

Statistically, this is a question about the observed proportion meeting a defined virologic threshold after a treatment course, rather than a direct comparison of outcomes between randomized treatments. A single-group result can describe outcomes among the analyzed participants, but without a concurrent comparator it cannot by itself separate treatment-related change from other explanations for the observed outcome. The registry record does not report a primary endpoint estimate, so even that descriptive result cannot be summarized from this record.

3. Trial Design

The registry identifies a phase 2, open-label, single-group study. Allocation is listed as not applicable, and masking is listed as none. The study title and description concern a fixed-dose combination of GS-7977 and GS-5885 for people with HCV genotype 1 and HIV coinfection. The stated enrollment is 50. The study is listed as completed, with a start date of 2013-06 and primary completion in 2014-09.

According to the design description, participants were to take one combination pill daily for 12 weeks. Monitoring with clinic visits and blood tests was described over a total of 60 weeks. The primary endpoint was assessed 12 weeks after treatment completion. These are descriptions of the planned treatment and follow-up schedule; they do not establish how completely participants followed the schedule or how many contributed endpoint data.

Because this is a single-group study, there is no concurrent control arm against which to estimate a treatment contrast. The two adverse-event groups in the registry are based on whether participants were taking antiretroviral agents. The record does not describe those groups as randomized or as comparable treatment arms. Differences between them therefore should not be read as causal comparisons.

The description says that the primary endpoint analysis included all subjects who received at least one dose of study treatment. The number who received treatment, the number with endpoint measurements, and the handling of participants without an endpoint measurement are not reported in the registry record. The record also does not report the statistical plan or any basis for the stated enrollment. A sample-size justification and details of interim analyses are not reported in the registry record.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis included all subjects who received at least one dose of study treatment.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Achieved SVR12 (HCV RNA <LLOQ 12 Weeks After Completion of Treatment), measured over 12 weeks after completion of treatment.

The primary endpoint is the percentage of participants achieving SVR12, defined in the record as a plasma HCV RNA level below 12 IU/mL by the Abbott real-time HCV assay, assessed 12 weeks after treatment completion. It is a binary outcome for each participant: the measurement either meets the stated threshold or it does not. The percentage summarizes the proportion meeting that definition among the endpoint analysis population.

SVR12 is used as a measure of virologic response after treatment has ended, rather than merely a measurement taken during dosing. A threshold-based endpoint makes the response definition explicit, but interpretation still depends on which participants were included, whether endpoint measurements were available, and how missing measurements were handled. Those details affect what population the reported percentage would represent.

The registry record specifies an analysis population consisting of subjects who received at least one dose. It does not report the number in that population, the number achieving SVR12, the resulting percentage, or the 95% confidence interval. Thus, the endpoint definition is available, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint estimate?

For a binary endpoint, each participant is classified according to whether the outcome definition was met. The response percentage is the proportion of participants in the analysis population who met that definition. Here, the definition is SVR12, based on a plasma HCV RNA level below 12 IU/mL at the specified follow-up. This proportion is descriptive: it summarizes outcomes in the participants included in the analysis. It is not by itself a comparison with another treatment.

The analysis population matters because a percentage depends on who is counted. The record says the primary analysis included all subjects who received at least one dose. It does not report how many participants received a dose, how many had an SVR12 measurement, or how participants without an endpoint result were treated analytically. These omissions prevent reconstruction or evaluation of the endpoint estimate.

What does a confidence interval add?

A confidence interval accompanies an estimate to express its statistical uncertainty under the analysis method. In general, it gives a range of values that are reasonably compatible with the observed data and the assumptions used to calculate the interval. It should not be read as a guarantee that the true value lies in that particular interval. The registry identifies a 95% confidence interval as the dispersion measure for the primary endpoint, but neither the estimate nor the interval limits are reported.

For a response percentage, precision is influenced by the number of participants contributing outcome information and by how responses are distributed. The registry's enrollment figure alone does not reveal the endpoint denominator because the primary population is defined by having received at least one dose, and the outcome data available for analysis are not stated. No interval can be inferred from the record without inventing information.

Why does the design affect interpretation?

Randomization and a concurrent comparator can support a direct estimate of the difference between treatment groups, subject to the trial's design and analysis assumptions. This study is listed as single-group, with allocation not applicable and no masking. As a result, it does not provide that kind of between-group treatment contrast. If an outcome estimate were reported, it would describe the analyzed study group; it would not by itself identify what would have happened to those same participants under a different treatment.

Open-label describes the lack of masking in the study record. For an objectively defined laboratory endpoint, the threshold is explicit, but open-label conduct and other study procedures can still matter for participant management, measurement, follow-up, and completeness of data. The registry record does not provide enough information to assess those processes in detail.

How should event proportions and group counts be read?

Safety entries report counts of participants with serious adverse events and other adverse events within the recorded antiretroviral-status groups. Counts describe how many participants were recorded with an event in a category, while the at-risk count gives the group denominator used in that entry. These are descriptive quantities. They do not establish that an event was caused by the study treatment, and they do not estimate a comparative risk against an untreated or randomized control group.

Over-dispersion is a general statistical issue that arises when variability in the data is greater than a simple model assumes. It can make standard errors and confidence intervals too optimistic if not addressed. That concept is especially relevant to some count outcomes, but the primary endpoint is binary, and the registry does not report a fitted model or enough outcome information to assess any model fit or over-dispersion. It would be inappropriate to assert that such a problem occurred in this study.

What do the planning illustrations represent?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between hypothetical arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the original study used those assumptions to design enrollment. The record does not report a trial-specific sample-size justification or statistical plan. Since it does not report the primary endpoint estimate, no recalculation from the posted primary outcome can be evaluated from the registry record.

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("Subjects With HIV and HCV on Antiretroviral Agents", "Subjects With HIV and HCV Who Are Not on Antiretro")
n      <- c(37, 13)
events <- c(36, 13)
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  Subjects With HIV and HCV on Antiretroviral Agents  37  36  97.3  85.8  99.9  86.2  99.5  86.2  99.4
ARM  Subjects With HIV and HCV Who Are Not on Antiretro  13  13  100.0  75.3  100.0  77.2  100.0  76.8  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and reports no analysis entries. It does not report a multiplicity adjustment, a hierarchy of tests, or a broader inferential plan. When several outcomes or hypotheses are tested, multiplicity can increase the chance of at least one false-positive finding unless the analysis accounts for the testing strategy. This is a general concern; the record does not establish what additional analyses were planned or performed.

The primary endpoint analysis population is described as all subjects who received at least one dose of study treatment. This is a treated-participant definition, not a statement that all enrolled participants were analyzed. The number who received treatment and the endpoint denominator are not reported in the registry record. Nor does the record say how missing SVR12 measurements were handled, whether participants with incomplete follow-up were counted as not achieving the endpoint, or whether any sensitivity analyses were used.

Missing outcome data can affect a response percentage if participants without measurements differ in outcome from those with measurements. The direction and size of any such effect cannot be determined without information about missingness and its handling. The registry record does not report the number of missing primary endpoint measurements or reasons for missingness.

The registry record also does not report an analysis plan, interim analyses, or a sample-size justification. Those details should not be inferred from the posted enrollment or the study's completed status. The absence of these details in the registry does not establish what may have appeared in documents outside the registry; it means those methods are not reported in the registry record.

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: pneumonia (7.7%).

The serious adverse-event entries are organized by antiretroviral-agent status. Among subjects with HIV and HCV on antiretroviral agents, the record lists 0 serious adverse events among 37 at risk. Among subjects with HIV and HCV who were not on antiretroviral agents, it lists 1 among 13 at risk. The registry lists pneumonia at 7.7% among the top serious terms. It does not report deaths for either group.

The record also lists other adverse events for these groups: 36 among 37 at risk in the group on antiretroviral agents, and 13 among 13 at risk in the group not on antiretroviral agents. These are descriptive registry counts, not comparisons between randomized treatment arms. The groups differ by antiretroviral-agent status, and the record does not establish that they are otherwise comparable.

These entries do not identify whether an event was caused by study treatment. They also do not provide event timing, severity details beyond the serious-event classification, or a controlled estimate of relative safety. The pneumonia percentage is a registry entry for a serious-event term; the record does not provide enough detail to infer its relationship to a particular group or to the study drug.

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

The record documents a study designed to assess a fixed-dose combination of GS-7977 and GS-5885 among people with HIV and HCV genotype 1. Its stated primary endpoint is SVR12, using a specified HCV RNA threshold after treatment completion. It also gives selected adverse-event counts and describes a daily treatment schedule and follow-up plan. These are useful features for understanding the trial's question and structure.

However, the primary endpoint result itself is not reported in the registry record. There is no reported response percentage or confidence interval to describe. Therefore, no claim about the observed level of SVR12, or its precision, can be supported from this record. The enrollment figure does not resolve that gap, because the number who received treatment and the endpoint analysis denominator are not stated.

The study's single-group, open-label design also means that a reported response percentage would not be a randomized comparison. A proportion observed after treatment could describe the outcomes in the analyzed group, but without a concurrent comparator it would not estimate the difference between this regimen and another strategy. The adverse-event groups are based on antiretroviral-agent status and should not be treated as controlled treatment arms.

Likewise, the safety entries are not proof that a treatment caused or prevented an event. They are descriptive counts, and details about attribution, timing, missing safety data, and a comparative analysis are not reported in the registry record. The registry record's reported figures should therefore be read as recorded observations with important limits, rather than as a complete account of treatment effects.

In short, the registry record establishes the endpoint definition and the study design, but does not report the primary result needed to quantify the response. It does not support a numerical estimate of efficacy or a causal efficacy or safety comparison.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary question is framed around a clearly specified binary virologic endpoint, while the registry record does not report the estimate for that endpoint. The threshold and timing are stated: plasma HCV RNA below 12 IU/mL at 12 weeks after treatment completion. Such specificity makes clear what would count as a response, but a defined endpoint is not a substitute for reporting its observed frequency and uncertainty.

The study also illustrates the distinction between a single-group description and a comparative treatment effect. Its design is listed as open-label and single-group, with allocation not applicable. Any observed response proportion would therefore characterize the analyzed participants, rather than provide a randomized contrast with a separate control group. Recognizing that distinction is essential when interpreting results from early-phase or otherwise noncomparative studies.

The treatment exposure and follow-up schedule are recorded, along with safety counts broken out by antiretroviral-agent status. The safety groups are not randomized treatment arms, so they cannot be used as a like-for-like comparison. Their figures can still describe what the registry recorded in each category, while leaving causal interpretation unresolved.

Finally, this record demonstrates why analysis populations, missing outcome handling, and uncertainty intervals matter. Enrollment alone does not reveal how many participants contribute to the primary estimate. The record states that the analysis included people who received at least one dose, but does not report the corresponding denominator, endpoint result, or interval. Without those details, statistical interpretation must remain focused on the design and the limits of what is reported.

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 key limitation for interpreting the study statistically is that the registry record does not report the primary endpoint estimate or its 95% confidence interval. It therefore does not show the observed SVR12 proportion or its precision. The record gives enrollment as 50 but does not state how many participants received at least one dose or contributed an endpoint measurement.

The single-group, open-label design provides no concurrent control group for estimating a comparative treatment effect. The antiretroviral-status categories listed for safety outcomes are not described as randomized arms and should not be interpreted as such. The record does not provide a causal comparison for either efficacy or safety.

Details needed to assess endpoint completeness are also absent. The number and reasons for missing SVR12 measurements, the treatment of missing outcomes, and sensitivity analyses are not reported in the registry record. The record does not describe the statistical plan, any interim analyses, or a trial-specific sample-size justification. It also does not report deaths for the safety groups.

Finally, the safety entries are limited to the recorded event categories and counts. The registry record does not give enough information to assess event attribution, timing, or differences in underlying characteristics between the antiretroviral-status groups. These limitations do not establish that an unreported analysis was or was not performed; they define what cannot be evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of A Combination Pill With GS-7977 and GS-5885 for Hepatitis C in People With HIV — NCT01878799.
• Registry record last updated 2016-09-15; status last verified 2016-07.
• Results first posted 2016-09-15.
• 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

This completed phase 2 study is listed as an open-label, single-group trial of a fixed-dose combination of GS-7977 and GS-5885 for people with HIV and HCV genotype 1. Enrollment was 50; the study start is listed as 2013-06 and primary completion as 2014-09. Participants were described as taking one pill daily for 12 weeks, with monitoring over a total of 60 weeks.

The primary endpoint was SVR12, defined as plasma HCV RNA below 12 IU/mL 12 weeks after treatment completion. The analysis population was described as subjects who received at least one dose. The percentage achieving the endpoint, its 95% confidence interval, the endpoint denominator, and missing-data handling are not reported in the registry record.

Safety counts are reported by antiretroviral-agent status, but these groups are not a randomized comparison. The registry record does not report a trial-specific sample-size justification or statistical plan.