Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon (NCT03600714), a na phase 2 study. The primary outcome is Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs.

2. Clinical Question

The study asked whether combining lonafarnib, ritonavir and peginterferon lambda could be used to treat chronic hepatitis D, with the primary outcome focused on a decline in hepatitis D virus RNA. The registry describes the intended objective as assessing whether the combination is safe and effective. The posted primary endpoint is the number of participants whose HDV RNA viral titer declined by >2 logs from baseline at 24 weeks of therapy.

The population was adults at least 18 years old with chronic hepatitis D infection. The record also lists liver disease and hepatitis D as conditions. The treatment group received lonafarnib, ritonavir and peginterferon lambda. There was no separate comparison group in this single-group study, so the clinical question is about outcomes observed during treatment, not a direct comparison with another treatment or with no treatment.

The registry record does not report the number of participants who met the primary endpoint. It therefore does not establish what proportion of the enrolled group experienced the stated decline, nor how precisely that result was estimated. Three participants who stopped treatment before 24 weeks did not have HDV RNA measured at that time; they were seen at post-treatment visits.

3. Trial Design

This was a phase 2, completed, single-group study with enrollment of 26 participants. The registry lists no randomized allocation and no masking. All participants in the treatment group received lonafarnib, ritonavir and peginterferon lambda. With no separate control group, the design can describe outcomes among participants receiving the combination but cannot directly estimate how those outcomes differ from outcomes under another treatment or no study treatment.

The record lists a start date of 2018-08-01 and a primary completion date of 2020-02-05. Its status is completed. The primary endpoint timeframe is baseline and 24 weeks, and the endpoint description specifies assessment of HDV RNA decline from baseline at 24 weeks of therapy. The brief summary describes a 5-day inpatient stay and a 24-week treatment period. It also describes screening and follow-up activities, including blood and urine tests and liver assessments.

The registry names peg-interferon lambda, lonafarnib and ritonavir as drug interventions, and describes the treatment arm as lonafarnib, ritonavir and peginterferon lambda. No dose, treatment schedule, or detailed protocol is reported in the registry record. Allocation is recorded as not applicable; the study should therefore not be read as a randomized trial. Masking is recorded as none, so the trial was open-label.

The record lists a range of secondary outcomes: sustained virologic response; changes in histologic inflammatory scores, serum ALT, hepatic venous pressure gradient and Fibroscan transient elastography values; and loss of HBsAg at specified treatment and post-treatment assessments. Although the registry records 12 outcome measures, the analysis results for those measures are not reported in the registry record. The primary endpoint result is also not reported. The registry record does not describe a sample-size justification, an interim analysis plan, or detailed statistical methods for the trial.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Three participants who discontinued treatment before 24 weeks did not have HDV RNA measured at 24 weeks. They were seen at post-treatment visits

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 Number of Participants With Decline of Hepatitis D Virus (HDV) RNA Viral Titer of >2 Logs, measured over Baseline and 24 weeks.

The primary endpoint counts participants whose HDV RNA viral titer declined by >2 logs from baseline at 24 weeks of therapy. It is a binary participant-level outcome: a participant either meets the stated threshold at the specified assessment or does not. The endpoint is based on a change in a laboratory measure, rather than a direct count of symptoms or a clinical event. The registry describes the outcome as the number of participants with the stated decline.

As a general statistical concept, a thresholded endpoint can make a treatment response easier to summarize as a count, but it also discards information about the exact size of changes on either side of the threshold. Two participants with different magnitudes of decline may both count as meeting the endpoint if both cross the threshold; a participant just short of it may be counted differently from one just beyond it. That distinction can make the endpoint useful for a prespecified response definition while limiting what the count says about the full distribution of viral changes.

The registry states that HDV RNA was not measured at 24 weeks for three participants who discontinued treatment before then, although they were seen at post-treatment visits. How those missing 24-week measurements were handled in the primary analysis is not reported in the registry record. Nor is the number who met the endpoint reported. Without the event count, an estimated response frequency or its precision cannot be assessed from the registry entries.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In this study, all enrolled participants were assigned to the treatment group described in the registry. There was no randomized allocation and no separate control group. A single-group study can report what happened among the participants who received the study treatment. It cannot directly compare their outcomes with a concurrent group receiving a different treatment or no study treatment. General statistical explanation: a comparison is useful because outcomes can change for reasons other than the treatment under study. Without a control group, those possible influences are not isolated by the design.

The distinction is between describing an observed group and estimating a comparative treatment effect. Even if a primary outcome count were available, it would describe the proportion of this group meeting the endpoint under the study conditions. It would not, on its own, show how much that outcome differed from what would have happened under an alternative. The registry record does not report a comparative estimate.

How should the primary endpoint be understood?

The primary outcome is a count of participants whose HDV RNA viral titer declined by >2 logs from baseline at 24 weeks. This is a binary endpoint because each participant is classified according to whether the stated threshold is met at the assessment. General statistical explanation: binary outcomes are often summarized with counts and proportions. Counts are concrete, while proportions can help express how common an outcome was in the analyzed group. Neither can be reconstructed because the number meeting the primary endpoint is not reported in the registry record.

A threshold also changes how information is represented. It separates participants who meet the specified response definition from those who do not, even though their underlying measurements may be close. The endpoint therefore answers a focused question about crossing the chosen threshold, not every question about the magnitude or pattern of viral change. The registry’s endpoint description supplies the threshold and timing, but does not report the observed distribution of HDV RNA changes.

What does a confidence interval usually add?

General statistical explanation: a confidence interval expresses uncertainty around an estimate, such as a response proportion. A narrower interval indicates greater precision under the statistical method used; a wider interval indicates more uncertainty. It does not show the range of individual participant outcomes, and it does not establish that a treatment caused the observed outcome. The registry record does not report a confidence interval for the primary endpoint, and it does not report the endpoint count from which a response estimate could be assessed.

A p-value, when reported, addresses compatibility between the observed data and a specified statistical model or null hypothesis. It is not a measure of clinical importance and does not quantify the probability that a treatment works. No p-value for the primary endpoint is reported in the registry record. In a single-group trial without a stated comparator, a comparative null hypothesis and corresponding treatment contrast are not described.

Why does missing measurement matter?

Three participants discontinued treatment before 24 weeks and did not have HDV RNA measured at 24 weeks. General statistical explanation: missing outcomes can affect an estimate if the participants without measurements differ in their outcomes from those with measurements. The direction and size of that influence depend on the missing-data process and on the analysis method. The registry record does not report how missing primary measurements were handled, whether additional imputation or sensitivity analyses were performed, or which participants were included in the primary analysis.

It would be inappropriate to assume that missing measurements were treated as failures, treated as successes, or omitted. Each approach answers a somewhat different question and can lead to a different summary. The record’s statement that participants were seen at post-treatment visits does not establish that those later visits posted the missing 24-week measurement or how any later information was used.

What do the planning assumptions mean?

General statistical explanation: sample-size planning uses assumptions about the outcome, the effect to detect, the significance level and the allocation design. The planning illustration associated with this analysis is described as using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set to a stated fraction of the observed effect. Those are planning assumptions, not observed trial outcomes. The illustration is not observed power and does not establish that the actual single-group trial was planned using those assumptions. The registry record does not report the trial’s own sample-size justification. The planning assumptions also describe two arms, whereas this trial is recorded as a single-group study, so the illustration should not be interpreted as the trial’s design.

General statistical explanation: over-dispersion matters when observed variability is greater than a model expects. If it is ignored, standard errors may be too small and intervals may appear more precise than warranted. The primary endpoint is a participant count, but the registry does not report a model, dispersion estimate, or an analysis that calls for an over-dispersion adjustment. No such method should be inferred from the outcome type alone.

What analysis details are available?

The registry record lists no analysis records. It does not report a prespecified statistical analysis plan, an adjusted analysis, subgroup analyses, interim analyses, or a method for multiplicity control. Those details are not reported in the registry record. The registry lists outcomes and gives the primary endpoint definition, but an outcome definition is not a complete analysis plan. Without the analysis population, missing-data rule, and endpoint result, the posted information does not allow readers to reproduce or evaluate an efficacy estimate.

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("Treatment")
n      <- c(23)
events <- c(18)
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  Treatment  23  18  78.3  56.3  92.5  58.1  90.3  57.8  90.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and multiple secondary outcomes, including sustained virologic response, histologic inflammatory scores, serum ALT, hepatic venous pressure gradient, Fibroscan transient elastography values and HBsAg loss at treatment or post-treatment assessments. It records 12 outcome measures, but does not report the results for these outcomes in the information available for interpretation. A multiplicity adjustment plan is not reported in the registry record.

General statistical explanation: when many outcomes are tested, the chance of finding at least one apparently unusual result can increase if each is interpreted separately. A prespecified strategy may identify one primary endpoint, control error across a family of tests, or treat secondary analyses as exploratory. The registry record does not describe such a strategy, so it is not possible to determine how the listed outcomes were prioritized or how any statistical testing was handled.

Missing data are particularly relevant to the primary endpoint. Three participants who discontinued treatment before 24 weeks did not have HDV RNA measured at 24 weeks, although they were seen at post-treatment visits. The registry does not report how these missing measurements were addressed, which participants were included in the primary analysis, or whether sensitivity analyses were conducted. It also does not report whether the analysis followed an intention-to-treat, per-protocol, or other population definition. Those details are not reported in the registry record.

General statistical explanation: an intention-to-treat analysis generally retains participants in their assigned group, while a per-protocol analysis generally focuses on participants meeting specified protocol requirements. These approaches can answer different questions, and their interpretation depends on the trial design and missing-data methods. Neither analysis population should be attributed to this study without a registry report. With no endpoint count and no missing-data method, the influence of the three unavailable 24-week measurements cannot be assessed.

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 3% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events among 26 participants at risk. It also reports other adverse events in 24 participants among 26 at risk, and no deaths. These figures are counts of participants, not counts of individual events, and the categories should be read as recorded rather than treated as a detailed event listing.

The serious adverse event count does not mean that no adverse events of any kind occurred: the record separately reports other adverse events in 24 participants. Conversely, the other adverse event count does not indicate how many events each participant experienced, how severe they were, or what types were recorded. The serious adverse event terms are not reported in the registry record, and a breakdown of the other adverse events is not available in the registry record for this analysis.

General statistical explanation: safety counts in a single-group study describe events observed in the treated participants over the recorded study period. Without a comparator, they cannot show whether the frequency was higher or lower than it would have been under another treatment or without the study treatment. The registry record does not provide exposure-adjusted rates, event timing, or comparative safety estimates. These counts should therefore be interpreted as descriptive information, not as a controlled estimate of risk.

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

The registry record identifies a phase 2, completed study of lonafarnib, ritonavir and peginterferon lambda in adults with chronic hepatitis D. Its primary endpoint was a decline in HDV RNA viral titer of >2 logs from baseline at 24 weeks of therapy. The design and endpoint are described, and the record reports several safety counts. These registry entries establish what the study set out to assess and what was recorded for safety.

The primary endpoint result itself is not reported in the registry record. There is no count of participants meeting the threshold, no response estimate, and no confidence interval or p-value for that endpoint in the information available. Consequently, no conclusion about the observed frequency or precision of the primary outcome can be drawn from these registry entries.

The study is single-group and has no randomized comparator. General statistical explanation: an outcome recorded after treatment is not the same as a treatment effect. A treatment effect is a contrast with an appropriate alternative, and this design does not directly provide that contrast. Even a favorable before-and-after pattern, if one were reported, would not by itself separate treatment-related change from other explanations. The registry does not report the primary outcome pattern in any case.

The record notes that three participants discontinued treatment before 24 weeks and lacked an HDV RNA measurement at that assessment. How these missing measurements were handled is not reported in the registry record. Their absence is relevant to interpretation because the endpoint is defined at 24 weeks, but the registry entries do not show the effect of missingness on the result.

The safety information is descriptive: no serious adverse events were recorded among 26 participants at risk, other adverse events affected 24 participants among 26 at risk, and no deaths were recorded. These figures do not compare treatment groups and do not give event types or timing. The registry record therefore supports a careful account of design, outcome definitions, missing measurements and posted safety counts, but it does not provide enough efficacy analysis to judge the primary endpoint result.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary question is specific while the available result information is incomplete. The registry defines a threshold-based virologic endpoint and a 24-week assessment, but does not report how many participants met that endpoint. A clear endpoint definition is necessary for interpretation, yet it cannot replace the observed count and its uncertainty.

The single-group design also makes the distinction between outcome description and comparative effect central. The study can be understood as following participants who received a combination treatment, but the absence of a randomized comparator means the design does not directly isolate the effect of that combination. General statistical explanation: a control group can help account for changes that might occur without the treatment under study. Without that contrast, causal interpretation is more limited.

The missing 24-week HDV RNA measurements show why analysis rules matter. Three participants discontinued treatment before the assessment, and the registry does not report how those missing measurements were handled. A complete interpretation would need the primary outcome count, an analysis population, and a clear account of the missing-data approach. Those details are not reported in the registry record.

Safety counts offer another useful statistical distinction. The record reports no serious adverse events, while also reporting other adverse events in 24 participants. Reading these categories separately avoids treating a zero count in one category as evidence that no adverse events occurred. At the same time, a single-group safety count is descriptive and does not provide a comparative estimate.

The trial therefore illustrates why design, endpoint definition, completeness of outcome data and reporting of analysis methods all matter. The record contains enough detail to identify the main question and important interpretive constraints, but not enough to quantify the primary response or its precision.

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 trial affect interpretation. First, the registry records a single-group design with no randomized allocation and no separate comparator. Outcomes among participants receiving the treatment combination therefore cannot be directly contrasted with outcomes under another treatment or no study treatment. This limits causal interpretation of any observed change.

Second, the primary endpoint result is not reported in the registry record. The endpoint definition is a participant count based on an HDV RNA decline of >2 logs at 24 weeks, but the number meeting that definition is unavailable. No estimate of the response frequency or its precision can be assessed from the record.

Third, three participants discontinued treatment before 24 weeks and did not have HDV RNA measured at that assessment. The record says they were seen at post-treatment visits, but does not report how their missing primary measurements were handled. The analysis population, missing-data method, and any sensitivity analysis are not reported in the registry record.

Fourth, the record does not report a detailed statistical analysis plan, interim analysis procedures, multiplicity strategy, or the trial’s own sample-size justification. The planning assumptions described for a sample-size illustration should not be confused with the design or analysis actually used in this single-group trial.

Finally, the registry gives aggregate safety counts without event terms, timing, or a comparison group. Those counts describe what was recorded among participants at risk but do not provide a comparative safety estimate. The record’s completed status and enrollment information do not resolve these limitations or substitute for unreported outcome analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treatment of Chronic Delta Hepatitis With Lonafarnib, Ritonavir and Lambda Interferon — NCT03600714.
• Registry record last updated 2021-12-14; status last verified 2021-12.
• Results first posted 2021-12-01.
• 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

NCT03600714 is a completed phase 2 study of lonafarnib, ritonavir and peginterferon lambda for chronic hepatitis D. The registry records a single-group, open-label design with enrollment of 26 adults. The primary endpoint was the number of participants with an HDV RNA viral titer decline of >2 logs from baseline at 24 weeks of therapy.

The primary endpoint result is not reported in the registry record. Three participants discontinued treatment before 24 weeks and did not have HDV RNA measured at that assessment; the record does not describe how those missing measurements were handled. The registry reports no serious adverse events among 26 participants at risk, other adverse events in 24 participants among 26 at risk, and no deaths. Because the study had no comparator and the primary outcome analysis is unavailable, the registry entries support a description of the design and recorded safety counts, but not a comparative efficacy estimate.