Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Participants With Nonalcoholic Steatohepatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Participants With Nonalcoholic Steatohepatitis (NCT03059446), a na phase 2 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (AE).

2. Clinical Question

The study was designed to continue open-label treatment for participants transitioning from either of two prior studies and to assess the long-term safety of continued cenicriviroc treatment. The primary endpoint is a count of participants with at least one treatment-emergent adverse event, rather than a measure of liver fibrosis improvement or another efficacy outcome.

Because the study had one treatment group and no concurrent comparator, its central statistical question is descriptive: what adverse events were recorded among participants who received treatment? The registry record does not report a randomized comparison of cenicriviroc with another treatment or with no treatment. Therefore, the posted safety counts do not establish how those outcomes would have differed under an alternative treatment or without cenicriviroc.

3. Trial Design

This was a Phase 2, open-label, single-group rollover study of cenicriviroc in adults with nonalcoholic steatohepatitis. Participants had previously taken part in either the CENTAUR study or the AURORA study. The registry describes the purpose as providing open-label treatment and assessing the long-term safety of continued cenicriviroc treatment.

The treatment group received cenicriviroc 150 mg once daily in the morning with food. Treatment continued until the study was terminated, for up to approximately 4 years. The primary endpoint’s follow-up period is described as Day 1 until termination, also up to approximately 4 years. The registry record reports enrollment of 167 participants. It lists the study as terminated, with a start date of 2017-02-14 and a primary completion date of 2021-01-05. The reason for termination is not reported in the registry record.

There was no masking and no randomized allocation. The registry identifies a single-group model and does not describe a like-for-like control group. These design features matter when interpreting the results: observed event counts describe the participants who received cenicriviroc, but the design does not isolate the treatment’s effect from other influences or show what would have occurred in a concurrent comparison group.

The safety population included all participants who received at least one dose of study drug. The record does not give further detail about how many enrolled participants received a dose or remained under observation for particular lengths of time. A participant count and a long maximum follow-up period do not, on their own, describe each participant’s exposure time.

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 who completed the CENTAUR study \[NCT02217475\] or the AURORA study \[NCT03028740\] were eligible for enrollment in this rollover study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population included all participants who received at least one dose of study drug.

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 Population included all participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (AE), measured over Day 1 until the study was terminated (up to approximately 4 years).

The primary endpoint was the number of participants with treatment-emergent adverse events. The registry defines an adverse event as an untoward medical occurrence in a participant administered a pharmaceutical product; it need not have a causal relationship with treatment. A treatment-emergent adverse event is an adverse event that occurs after a participant receives study drug.

This endpoint is used to describe safety during treatment. Counting participants with an event gives a straightforward summary of how many people in the safety population experienced one or more events during the stated follow-up period. It does not count every event separately, measure event severity by itself, or establish that treatment caused an event.

The endpoint timeframe was Day 1 until the study was terminated, up to approximately 4 years. The registry record reports 40 participants with serious adverse events among 167 at risk and 98 participants with other adverse events among 167 at risk. These are safety counts, not estimates of a treatment difference. The record does not provide a treatment-effect estimate or confidence interval for the primary endpoint.

Because the study was a single-group rollover study, the endpoint can characterize events recorded among treated participants, but it cannot serve as a controlled comparison of safety across treatment options.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main outcome is a participant count: the number of people experiencing a treatment-emergent adverse event. A count is useful when the clinical question concerns how many participants had an event, rather than how many episodes occurred. In this study, an event qualified as treatment-emergent if it occurred after a participant received study drug. The endpoint does not, by definition, require that the drug caused the event.

What a participant count captures

A participant-level count records whether participants experienced the defined outcome during the observation period. If one participant experiences repeated events, a count of participants with at least one event does not represent the number of episodes. Event-level summaries and participant-level summaries answer different questions, so their denominators and meanings should not be treated as interchangeable.

The endpoint timeframe ran from Day 1 until study termination, up to approximately 4 years. Participants may have had different lengths of observation, but participant-specific follow-up is not reported in the registry record. In general, when follow-up time differs, a simple participant count does not describe the rate of events per unit of time. A time-based analysis would need suitable event timing and exposure information; such an analysis is not reported in the registry record.

Why the design limits comparisons

The trial used one open-label treatment group and no randomized comparison group. In general, randomization helps balance measured and unmeasured factors between groups, while a concurrent control helps show how outcomes compare over the same period. Neither a randomized comparison nor a concurrent control is described for this study. Consequently, the reported adverse event counts are descriptive and cannot distinguish treatment effects from other explanations for events.

Open-label means treatment was not masked. In general, knowing the treatment can influence reporting, assessment, or management of events. The registry record does not describe additional procedures that would establish whether such influences occurred in this study.

What inferential statistics would add

A confidence interval is a range of values compatible with the data under a specified statistical method. In general, it communicates uncertainty around an estimate; it does not guarantee that the true value falls within the interval, and it does not correct for limitations in study design. The registry record does not report confidence intervals or an inferential estimate for the primary endpoint. It also reports no analyses in the posted results. Without a comparator and a reported analysis, there is no posted treatment contrast to interpret.

General statistical tests can assess whether observed data are compatible with a stated null hypothesis, but a p-value alone does not quantify clinical importance or establish causation. No p-value or hypothesis test for the primary endpoint is reported in the registry record. The available results should therefore be read as counts and event-term descriptions, not as a test of whether cenicriviroc changed the probability of an event.

Planning illustrations are not observed power

The planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The illustration is explicitly not the trial’s own design. Its hypothetical two-arm assumptions do not match this single-group, non-randomized study, and any resulting sample-size values are planning illustrations rather than evidence about the study’s actual power. They are not observed power and do not change the interpretation of the safety counts.

The registry record does not report the protocol’s sample-size justification, a prespecified statistical analysis plan, or the basis for selecting any planned statistical methods. It is therefore not possible to determine from this record whether the planning illustration reflects the investigators’ original design decisions.

How to read event categories

The registry provides separate serious and other adverse event figures. In general, seriousness is a classification of an event, not a judgment that the treatment caused it. The registry definition of an adverse event expressly does not require a causal relationship with treatment. The serious-event listings and participant counts should therefore be interpreted as safety descriptions rather than causal conclusions.

Over-dispersion is a general statistical issue that arises when count data vary more than a chosen model expects; it can make uncertainty estimates from that model too narrow. The registry record does not report a count model or an analysis of event rates, so there is no reported model-based result to assess for over-dispersion. For this endpoint, the posted participant counts remain the most direct descriptive quantities available.

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("Cenicriviroc (CVC) 150 mg")
n      <- c(167)
events <- c(140)
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  Cenicriviroc (CVC) 150 mg  167  140  83.8  77.4  89.1  77.5  88.6  77.5  88.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record reports one primary outcome measure and no posted analyses. It does not report a multiplicity adjustment, a hierarchy of statistical tests, or an analysis plan for handling multiple comparisons. Multiplicity arises when several hypotheses are tested; testing more hypotheses can increase the chance of at least one nominally positive finding. Since no inferential analyses are reported, the record does not permit an assessment of multiplicity control.

Missing data methods are not reported in the registry record. The safety population included all participants who received at least one dose of study drug, but the record does not describe missing outcome data, withdrawals, exclusions from particular analyses, or how incomplete follow-up was handled. It also does not provide participant-level follow-up durations. These details matter because adverse events may be observed over different periods, and incomplete observation can affect what is recorded.

The registry reports 167 participants at risk for both the serious and other adverse event summaries. This does not establish that every participant had the same follow-up duration or complete event reporting. The posted results do not include a missingness analysis or sensitivity analysis.

In general, an analysis population defines which participants contribute to a result. The safety population definition is stated, but the record does not describe additional analysis populations or a separate population for efficacy outcomes. Since the endpoint is a safety count and there are no posted analyses, interpretation is limited to the descriptive results and population definition in the registry 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: angina pectoris (1.8%), cellulitis (1.8%), dehydration (1.8%), acute kidney injury (1.8%), cholecystitis acute (1.2%).

The registry reports 40 participants with serious adverse events among 167 at risk, 98 participants with other adverse events among 167 at risk, and one death. These are counts from the single cenicriviroc group. Serious and other adverse event categories are presented separately; the registry record does not state that they are mutually exclusive, so the participant counts should not be added.

The top serious adverse event terms are listed with percentages: Angina pectoris, Cellulitis, Dehydration, and Acute kidney injury at 1.8% each; Cholecystitis acute and Pneumonia legionella at 1.2% each. The record does not give term-specific counts in this summary or explain the percentage denominator. These listings do not establish that cenicriviroc caused the events.

The adverse event definition allows events without a causal relationship to treatment. The record does not report attribution for the listed events or the death. These figures describe reported safety observations, not a comparative risk estimate.

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

The registry results show that adverse events were recorded among participants receiving cenicriviroc in an open-label rollover study. The primary endpoint counted participants with treatment-emergent adverse events, and the safety summaries report serious and other event counts. The record also lists selected serious event terms and reports one death. These findings are relevant as descriptive information about the treated cohort during the study’s stated observation period.

They do not show whether the event counts were higher or lower than they would have been with another treatment or without treatment. The study had no concurrent comparator and no random allocation. It also does not report a comparative estimate, confidence interval, or statistical test for the primary endpoint. Therefore, the posted data do not quantify a treatment effect or establish that cenicriviroc caused or prevented any event.

The listed serious-event terms and the death should be interpreted with the same caution. The registry definition of an adverse event does not require a causal link to treatment, and attribution for individual events is not reported. Nor do the counts alone describe event duration, recurrence, severity beyond the serious classification, or each participant’s time under observation.

The study’s rollover design addresses continued treatment among participants who had taken part in prior studies. It is not a controlled test of efficacy. The primary outcome is a safety endpoint, and the registry record does not report an efficacy outcome analysis. The findings therefore do not answer whether cenicriviroc improves liver fibrosis or changes the course of nonalcoholic steatohepatitis.

In general, interpretation of safety counts depends on the population observed, the duration of observation, event definitions, and completeness of reporting. The record defines the safety population and gives a maximum follow-up period, but does not report individual exposure time or missing-data handling. The counts should be understood as the safety information reported for this study, with those design and reporting limits in mind.

14. Why This Trial Matters Statistically

This study is statistically notable because its rollover design and single-group structure shape what can be learned from its results. Long-term follow-up can describe adverse events observed during continued treatment, while the absence of a concurrent control means those observations cannot be translated into a comparative treatment effect. The distinction between describing events and estimating a treatment effect is central to reading the registry results accurately.

The primary endpoint counts participants with treatment-emergent adverse events, an intuitive safety summary. But participant counts do not capture how many episodes occurred, how long participants were observed, or the rate of events over time. The follow-up period could extend until termination for up to approximately 4 years, and participant-specific observation times are not reported. This makes it important not to treat the counts as if they represented identical exposure for every participant.

The registry also illustrates why safety-event attribution requires care. An adverse event can occur after treatment begins without being caused by treatment. The serious adverse event figures, selected event terms, and death are meaningful observations for the cohort, but without a comparator or attribution details they do not establish causality.

Finally, the planning illustration uses hypothetical two-arm assumptions, while the actual study is a single-group rollover. Keeping planning calculations separate from observed results prevents a hypothetical sample-size exercise from being mistaken for the trial’s design rationale or statistical evidence. The registry record does not report the study’s own sample-size justification or a comparative analysis. These distinctions help preserve the proper scope of the conclusions: descriptive safety reporting, not a controlled estimate of benefit or harm.

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 absence of a randomized, concurrent comparison group is a central limitation for causal interpretation. The study was open-label and single-group, so the reported adverse event counts cannot show how outcomes would have differed under another treatment or no treatment. The rollover population had participated in prior studies, and the registry record does not report additional details about how those participants were selected for continued treatment.

The registry reports enrollment of 167 and an at-risk count of 167 for each adverse event summary, but does not provide participant-specific follow-up or exposure time. Follow-up was described as Day 1 until study termination, up to approximately 4 years. Unequal observation time may affect the opportunity to record events, and no time-to-event or event-rate analysis is reported.

The record does not report confidence intervals, comparative estimates, p-values, missing-data methods, or a statistical analysis plan. It does not state the reason for termination, the attribution of individual adverse events, or the cause of the reported death. The percentages attached to the listed serious event terms are not accompanied by term-specific counts or an explanation of the percentage denominator.

The primary endpoint measures participants with treatment-emergent adverse events, not efficacy. The registry record does not report an efficacy analysis, so these results cannot answer whether treatment affected liver fibrosis or another disease outcome. The planning illustration is not the trial’s own design and does not address the lack of a control group.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rollover Study of Cenicriviroc for the Treatment of Liver Fibrosis in Participants With Nonalcoholic Steatohepatitis — NCT03059446.
• Registry record last updated 2022-02-02; status last verified 2021-09.
• Results first posted 2022-02-02.
• 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

NCT03059446 is a Phase 2, open-label, single-group rollover study of cenicriviroc for participants with nonalcoholic steatohepatitis who had participated in either the CENTAUR or AURORA study. The treatment was cenicriviroc 150 mg once daily in the morning with food, until termination. The registry reports enrollment of 167, a start date of 2017-02-14, a primary completion date of 2021-01-05, and terminated status.

The primary endpoint counted participants with treatment-emergent adverse events from Day 1 until termination, up to approximately 4 years. The registry reports 40 participants with serious adverse events and 98 with other adverse events, each among 167 at risk, and one death. Selected serious event terms are listed with percentages. No randomized comparison or posted statistical analysis is reported. These results are descriptive safety findings and do not establish causality or a comparative treatment effect.