Evaluation of Safety, Tolerability, and Antiviral Activity of ACH-0143102 Plus Ribavirin In Treatment-naive Hepatitis C Virus Infection Genotype 1b Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Safety, Tolerability, and Antiviral Activity of ACH-0143102 Plus Ribavirin In Treatment-naive Hepatitis C Virus Infection Genotype 1b Participants (NCT01700179), a na phase 1 study. The primary outcome is Sustained Virologic Response At 12 Weeks (SVR12).

2. Clinical Question

This was a pilot study of treatment-naive participants with chronic genotype 1b infection. Its stated purpose was to evaluate safety, tolerability, and antiviral activity during treatment with ACH-0143102 plus ribavirin. The primary outcome measure was SVR12, a binary outcome: each participant either met the stated virologic criterion at the specified follow-up point or did not.

The question is descriptive rather than comparative. With no control group, the study cannot directly estimate how outcomes would have differed under another treatment or under no study treatment. The endpoint definition identifies what was to be measured, but the registry record does not report the number or percentage of participants who achieved SVR12. It therefore does not supply the primary outcome result needed to describe the observed antiviral response.

3. Trial Design

The registry record describes a phase 1b, open-label, pilot study with a single-group design. It lists 8 participants and no allocation to competing study arms. The study is marked completed. Its recorded start is 2012-09 and its primary completion is 2013-09.

All participants in the listed group received ACH-0143102 plus ribavirin. The regimen specified an ACH-0143102 loading dose of 225 milligrams on Day 1, followed by maintenance doses of 75 milligrams on Days 2-84. Ribavirin was weight-based and given as per label on Days 1-84. The official title describes oral ACH-0143102 administered in combination with ribavirin for 12 weeks. The record identifies the population as treatment-naive participants with chronic hepatitis C virus infection, genotype 1b.

Open-label means the registry does not describe masking of treatment assignment; masking is listed as none. In a single-group study, the recorded outcomes describe the participants receiving the regimen, rather than a contrast between separately assigned groups. This design can document what was observed in the enrolled group, but it does not provide a concurrent control for separating treatment-related changes from other influences.

The registry record does not report a statistical analysis plan, a sample-size justification, interim analyses, or details of the analysis population. The posted record also does not give the SVR12 count or percentage. The accompanying results displays may help organize the available information, but they cannot substitute for an unreported endpoint result or establish a between-group comparison.

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 screened within 4 weeks (-28 to -1 days) before administration of the study drug. Participants who meet all eligibility criteria were instructed to arrive at the study center on the baseline day.

Overall Study

Reasons for not completing this period:

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 analysis population for baseline characteristics was all enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Sustained Virologic Response At 12 Weeks (SVR12), measured over 12 weeks following the last dose.

The primary endpoint is sustained virologic response at 12 weeks, abbreviated SVR12. The registry defines it as hepatitis C virus ribonucleic acid below the limit of quantification at the assessment 12 weeks following the last dose. It is expressed as a percentage of participants, so it is a binary outcome summarized across the group: whether each participant met the virologic threshold at the specified time.

As a general statistical concept, a fixed-time binary endpoint provides a clearly defined status for each participant at a particular assessment point. Summarizing those statuses as a percentage can describe the frequency of the outcome in the study group. SVR12 is used as a measure of sustained virologic response after treatment has ended; the registry record makes the timing and laboratory threshold part of the endpoint definition.

The time point matters to interpretation. This is not an on-treatment measurement: the stated assessment is 12 weeks following the last dose. The endpoint definition alone, however, is not the result. The registry record does not report how many participants met the criterion, the percentage, or an uncertainty interval. Consequently, the primary endpoint can be described, but its observed value cannot be summarized from this record.

The record lists the endpoint as a percentage of participants and identifies the parameter as a number. It does not give a more detailed account of endpoint adjudication, handling of missing assessments, or the laboratory procedures used. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry record is limited. It identifies a binary primary outcome, a single treated group, enrollment of 8, and the endpoint timing and definition. It does not describe the statistical procedure used to analyze SVR12, provide a confidence interval, or report a primary outcome value. The explanations below are general statistical context, not a claim about methods used in this study.

What does a binary endpoint summarize?

A binary endpoint classifies each participant according to whether a defined event or state occurred. For this study, the record defines the state as hepatitis C virus ribonucleic acid below the limit of quantification 12 weeks following the last dose. A group summary can express the number meeting that definition as a percentage of those assessed. The registry record identifies the measure as a percentage of participants but does not provide the observed SVR12 count or percentage.

Such a summary is straightforward to interpret as a description of the enrolled group, provided the denominator and handling of unavailable measurements are clear. Here, the endpoint record does not describe missing-assessment rules or identify a specific analysis population. It is therefore not possible to determine from the posted information which participants, if any, were included in the endpoint denominator.

What would a confidence interval add?

As a general concept, a confidence interval gives a range of values compatible with the observed data under a stated statistical procedure. It communicates uncertainty around an estimate; it does not convert an estimate into a guarantee about the true value. For a percentage, the interval can show how imprecisely the observed proportion is estimated. No SVR12 estimate or confidence interval is reported in the registry record, so precision cannot be assessed for the primary endpoint.

Small study groups generally provide less information for estimating a proportion than larger groups, and the observed estimate can be sensitive to individual outcomes. This is a general property of estimation, not a new result for this trial. A confidence interval, if reported, would help readers understand that uncertainty, but it would not address the lack of a comparator or establish a causal effect.

Why does the single-group design matter?

In a single-group study, outcomes are described for participants receiving the recorded regimen. A comparison with another treatment requires a suitable comparator group and an analysis that accounts for how groups were formed. Neither a concurrent comparator nor random allocation is described. Thus, the registry record supports descriptive summaries for the group, but not a randomized treatment contrast.

Open-label status means the study is recorded as having no masking. As a general matter, knowledge of treatment assignment can affect some aspects of care, reporting, or assessment, depending on the outcome and study procedures. The registry record does not describe how such risks were managed. The primary endpoint uses a laboratory threshold, but no further information about assessment procedures is reported.

What do the sample-size illustrations mean?

The sample-size assumptions associated with the page describe planning illustrations based on the observed effect, rather than the trial's own design. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are assumptions for the illustrations, not evidence that this single-group study used those assumptions to plan enrollment. The registry record does not report its sample-size justification.

Sample-size calculations estimate how many participants a hypothetical design might require under specified assumptions. They are not measures of the probability that this completed study found a true effect. In particular, a planning illustration must not be interpreted as observed power. The assumptions described for a two-arm comparison also do not change the actual design recorded here, which has one group and no concurrent comparator.

What statistical details remain unavailable?

The registry record does not report the analysis method for the primary endpoint, a confidence interval, a hypothesis test, an interim analysis, or a multiplicity procedure. It also does not specify analysis populations, missing-data handling, or a statistical analysis plan. Without these details, readers cannot determine whether the posted outcome was intended to be analyzed with an adjusted method, how incomplete follow-up was handled, or whether multiple analyses were planned.

General statistical methods can describe how binary outcomes are summarized and how uncertainty is assessed, but those explanations should not be mistaken for the methods of this trial. For this record, the sound interpretation is to distinguish clearly between the stated endpoint and design, the recorded safety counts, and outcome or analysis details that are not reported.

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("ACH-0143102 Plus Ribavirin")
n      <- c(8)
events <- c(4)
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  ACH-0143102 Plus Ribavirin  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure: SVR12, assessed 12 weeks following the last dose. It does not report a multiplicity plan, such as how the interpretation of statistical tests would account for more than one outcome or analysis. The record lists no analyses. That absence does not establish whether analyses were conducted outside the posted registry information; it means they are not reported in the registry record.

As a general statistical concept, multiplicity arises when several hypotheses or outcomes are assessed, because repeated testing can affect how likely a result is to appear notable by chance. A prespecified approach can make the intended interpretation clearer. No such approach is described, and no test result for SVR12 is posted. Accordingly, there is no reported inferential result whose multiplicity adjustment can be evaluated.

The record does not explain how missing SVR12 assessments were handled, whether participants with unavailable measurements were excluded or classified in a particular way, or what analysis population was used. It also does not report the number assessed for the endpoint. These omissions matter because a percentage depends on its denominator and the rules used for participants without an observed endpoint.

The statistical analysis plan, sample-size justification, and interim-analysis procedures are not reported in the registry record. The planning illustrations elsewhere on the page are not the trial's own design justification and should not be used to fill these gaps. Without the analysis population, missing-data rules, and endpoint result, readers cannot reconstruct the primary analysis from the registry information.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety summary identifies 8 participants at risk for the serious adverse-event category, with 0 affected. It separately identifies 8 participants at risk in the other adverse-event category, with 6 affected. These are counts for the ACH-0143102 plus ribavirin group. They describe what is recorded in this small treated group and are not comparative estimates.

The registry record does not list serious adverse-event terms. The deaths field has no numeric value, so deaths are not reported in the registry record. The category label for the other events is not defined further in the posted information; the count should therefore be read using the registry's category as recorded rather than given a more specific interpretation.

As a general statistical point, event counts from a group of this size have limited ability to characterize uncommon outcomes or estimate how event frequency would compare with another group. A zero count in the serious category means no participants were recorded as affected there; it does not establish that the underlying risk is zero. Since there is no concurrent comparator, the counts cannot show whether risks differ from those under another treatment.

These safety figures should be kept distinct from the primary SVR12 endpoint. The registry record reports the safety counts but does not report the SVR12 result. The counts alone do not establish an overall safety profile or a comparative benefit-risk assessment.

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

This record shows that a completed phase 1b, open-label, single-group pilot study enrolled 8 treatment-naive participants with chronic genotype 1b hepatitis C. The group received ACH-0143102 plus ribavirin according to the listed regimen. The primary endpoint was SVR12, defined by the stated viral RNA threshold at 12 weeks following the last dose. The posted safety summary records 0 of 8 participants affected in the serious adverse-event category and 6 of 8 in the other adverse-event category.

What the record does not show is the observed SVR12 result. It gives no number or percentage meeting the primary endpoint, and no uncertainty interval. Therefore, the central antiviral outcome cannot be described quantitatively from the registry record. The study's stated purpose is not a substitute for a result, and no conclusion about the frequency of response in this group follows from the endpoint definition alone.

The design also sets limits on what the study can establish. There is no concurrent comparator and no randomized comparison. As a general statistical principle, outcomes in a single group do not reveal how those same participants would have fared under another approach. The safety counts are descriptive and cannot show a comparative risk difference.

The study is a pilot with enrollment of 8, so its recorded counts are limited to this enrolled group. Small groups generally provide limited information about less common events and the precision of an outcome estimate. Here, the primary endpoint estimate and its precision are not reported at all. That limitation is separate from the design's lack of a comparator.

The registry record also does not report a statistical analysis plan, analysis populations, missing-data rules, or multiplicity procedures. Sample-size planning illustrations displayed with the page are hypothetical planning aids, not observed power and not a reconstruction of the study's original planning. The appropriate reading is consequently narrow: the registry documents the study design, endpoint definition, and posted safety counts, but it does not provide the primary endpoint result or enough analysis detail for a fuller statistical assessment.

14. Why This Trial Matters Statistically

This study matters statistically as an example of the distinction between an endpoint definition and an endpoint result. The registry record clearly identifies SVR12, its timing, and the virologic threshold, but does not report how many participants met that definition. A well-described outcome question does not by itself tell readers what was observed. For interpretation, the estimate and its uncertainty are essential pieces of the evidence.

The single-group design is also important. It gives a structure for describing outcomes among participants receiving ACH-0143102 plus ribavirin, but it does not support a direct comparison with a control group. The record is open-label and has no masking, and it lists no randomized allocation. Those design features should shape the claims that can be made: the posted counts are descriptive, not comparative.

Enrollment of 8 highlights another general statistical issue: small studies often provide limited information about the precision of estimates, particularly for event outcomes. The record reports safety counts, but no uncertainty intervals. It reports no SVR12 count or percentage at all. The latter is not simply an issue of imprecision; the primary result is absent from the posted information.

The planning illustrations are useful only as planning illustrations. They do not establish the study's original rationale for enrollment, demonstrate observed power, or provide a substitute for a missing endpoint result. This distinction matters whenever hypothetical calculations appear alongside registry outcomes.

More broadly, the record shows why readers should separate what is documented—the design, regimen, endpoint definition, enrollment, and safety counts—from what is not reported, including the primary outcome result and analysis plan. That separation helps prevent a stated objective or a planning assumption from being mistaken for an observed finding.

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.

Several limitations specific to this study constrain interpretation. It was a single-group, open-label pilot study, with no concurrent comparator and allocation listed as not applicable. The design therefore does not provide a randomized comparison. The results, where recorded, describe participants receiving ACH-0143102 plus ribavirin rather than a contrast with another group.

Enrollment was 8. This small group limits how much information the study can provide about outcome frequencies and safety events. The registry reports 0 of 8 participants affected in the serious adverse-event category and 6 of 8 in the other adverse-event category, but those counts do not establish comparative risks or rule out uncommon events. No serious adverse-event terms are listed, and deaths are not reported in the registry record.

The primary endpoint is defined, but the registry record does not report its observed count or percentage. It also provides no confidence interval or other measure of uncertainty for SVR12. This prevents assessment of the response estimate, not merely a precise assessment of it. The record does not identify the analysis population, the number assessed, or how missing endpoint data were handled.

Important statistical procedures are also not reported in the registry record. These include the statistical analysis plan, sample-size justification, interim analyses, and multiplicity procedures. The sample-size assumptions displayed with the page are planning illustrations and should not be treated as the study's own design rationale or as observed power.

Finally, the posted information provides limited detail on endpoint assessment and the definitions applied to the other adverse-event category. These limitations are about the information available in the registry record; they should not be taken to imply that unreported procedures or results did not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Safety, Tolerability, and Antiviral Activity of ACH-0143102 Plus Ribavirin In Treatment-naive Hepatitis C Virus Infection Genotype 1b Participants — NCT01700179.
• Registry record last updated 2023-08-29; status last verified 2023-08.
• Results first posted 2014-10-03.
• 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 1b study enrolled 8 treatment-naive participants with chronic hepatitis C virus infection, genotype 1b. It was open-label and single-group, with no concurrent comparator. Participants received ACH-0143102 plus ribavirin for 12 weeks, using the dosing schedule described in the registry record.

The primary outcome was SVR12, defined as hepatitis C virus ribonucleic acid below the limit of quantification 12 weeks following the last dose. The registry record does not report the SVR12 count or percentage. The safety summary records 0 of 8 participants affected in the serious adverse-event category and 6 of 8 affected in the other adverse-event category; deaths are not reported in the registry record.

The record does not report a statistical analysis plan, analysis populations, missing-data handling, or a sample-size justification. The available information supports a description of the design and posted safety counts, but not a quantitative interpretation of the primary endpoint or a controlled treatment comparison.