Titrating-Dose of Lonafarnib in Combination With Ritonavir: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Titrating-Dose of Lonafarnib in Combination With Ritonavir (NCT02527707), a na phase 2 study. The primary outcome is Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer.

2. Clinical Question

This question is about change over time within the treated group, not a contrast between randomized treatment groups. The study description identifies safety, tolerability, pharmacokinetics, and pharmacodynamic activity as its areas of evaluation. The primary endpoint focuses on HDV RNA titer, a virologic measurement, while a listed secondary outcome concerns the number of patients with a 1 Log reduction from baseline by timepoint. The registry record does not give the numerical result for either outcome.

The dose escalation was conditional on tolerability, according to the arm description. That makes the endpoint a summary of a treatment strategy involving escalating doses as tolerated; it is not described as an effect attributable to one fixed lonafarnib dose. Without a comparator group or a reported endpoint estimate, the record does not establish how the observed change compares with what would have occurred without treatment or under another regimen.

3. Trial Design

This is a phase 2, open-label, single-group study of lonafarnib in combination with ritonavir in patients chronically infected with HDV. The registry record lists enrollment of 15, allocation as NA, and masking as none. No parallel control group is described, so the design does not support a like-for-like treatment comparison within the trial.

The treatment group is named lonafarnib/ritonavir. Lonafarnib starts at 50 mg BID with ritonavir 100 mg BID, and is escalated to lonafarnib 75 mg BID and then 100 mg BID as tolerated. The arm description gives a treatment duration of 6 months and a follow-up duration of 6 months for each patient. The primary endpoint timeframe is baseline and Week 24, also described as 6 months.

The record identifies the study as completed, with a start of 2015-09 and primary completion of 2016-08. These dates and the completed status describe the registry entry; they do not indicate whether all planned assessments were obtained or how many participants contributed data at each timepoint. Those details are not reported in the registry record.

Because the study is open-label and single-group, there is no blinded treatment assignment and no randomized control group stated. Changes over time may be described for participants receiving the regimen, but this design alone cannot separate treatment-associated change from other influences such as the natural course of infection, changes over time, or measurement variability. The registry record does not report a protocol-level account of the design rationale, dose-escalation decision rules beyond “as tolerated,” or the statistical plan.

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:

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 Change From Baseline to Week 24 in Mean Hepatitis D Virus (HDV) Ribonucleic Acid (RNA) Titer, measured over Baseline and Week 24 (6 months).

The primary endpoint is change from baseline to Week 24 in mean HDV RNA titer, measured in log IU/mL. The registry record describes the measure as a mean of a continuous measure and identifies standard deviation as its dispersion measure. The timeframe is baseline and Week 24, corresponding to 6 months.

HDV RNA titer quantifies viral RNA in a clinical sample. A change-from-baseline endpoint summarizes how the measured value differs at a later assessment from the participant’s starting value. The mean describes the group’s average change, while the standard deviation describes how much individual values vary around that average. These statistics answer different questions: the average characterizes the group-level pattern, and the standard deviation characterizes spread among the observations.

A change endpoint is used to focus on movement from each participant’s baseline rather than only the Week 24 level. In a single-group study, however, a before-and-after change is not itself a controlled estimate of what the treatment caused. The registry record does not report the mean change, its standard deviation, a confidence interval, or a test of the endpoint. Consequently, the magnitude and precision of the endpoint result cannot be assessed from the registry record.

The secondary outcome is the number of patients with a 1 Log reduction from baseline by timepoint. Its numerical results and the timepoints with available observations are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary endpoint: change from baseline to Week 24 in mean HDV RNA titer, with values expressed in log IU/mL. It identifies the summary as a mean and the dispersion measure as standard deviation. It does not report the statistical test, model, estimation procedure, confidence interval method, or covariate adjustment, so the analysis actually used is not reported in the registry record.

What a mean change represents

In general, a change-from-baseline analysis compares a later measurement with a participant’s starting measurement and then summarizes those changes across the group. A mean change is the arithmetic average of the participant-level changes included in the analysis. It gives a compact description of the group’s average movement, but does not show whether most participants changed similarly or whether a smaller number of larger changes influenced the average. The registry record does not state exactly how missing baseline or Week 24 measurements were handled.

What the standard deviation adds

In general, a standard deviation describes the spread of individual observations around a mean. A smaller standard deviation indicates observations clustered more closely around the mean; a larger one indicates more variability. It is not a measure of the precision of the estimated mean. Precision is commonly described with a standard error or a confidence interval, neither of which is reported for this primary endpoint in the registry record. The standard deviation value itself is also not reported.

How a confidence interval would be read

In general, a confidence interval presents a range of effect estimates compatible with the data and the interval’s statistical assumptions. A narrower interval indicates greater precision than a wider one, though precision does not determine whether an effect is clinically important. A confidence interval for this endpoint could help readers judge both the estimated change and the uncertainty around it. No such interval is reported in the registry record, so neither the estimate’s precision nor a plausible range can be assessed.

Why a comparison group matters

In general, measuring an outcome before and after treatment can describe a temporal change within participants. It does not, on its own, separate a treatment effect from other reasons the outcome might change over time. A concurrent comparison group can help estimate the difference in outcomes between treatment strategies, especially when treatment assignment is randomized. This trial is recorded as single group, with allocation listed as NA; no control group is described. Therefore, a within-group change, even if reported, would not be a randomized comparative treatment estimate.

Why variation and over-dispersion matter

In general, the choice of statistical model should reflect the kind of outcome and its variability. Over-dispersion means that observed variation exceeds what a model’s assumed distribution would predict. If a model ignores over-dispersion, its uncertainty estimates can be too small, making results appear more precise than they are. The primary endpoint is a continuous mean measure, and the registry record names standard deviation as its dispersion summary. It does not report an over-dispersion assessment or a model, so no conclusion about model fit or variance assumptions can be drawn.

How to distinguish estimation from testing

In general, an estimate describes the size and direction of an effect, while a hypothesis test evaluates data against a specified null hypothesis under a statistical procedure. A p-value, if reported, would not provide the effect size or its clinical meaning and would not replace an interval estimate. The registry record does not report a p-value or the test used for the primary endpoint. It also does not provide enough information to reconstruct an unadjusted analysis from summary statistics.

Planning calculations are not trial outcomes

In general, sample-size calculations describe the number of participants that might be needed under stated assumptions; they are not observed results and do not establish the precision actually achieved. Planning illustrations based on an observed effect are also different from a prospective design justification. The registry record does not report a sample-size justification or a statistical plan explaining the assumptions used in designing this study. The trial itself is described as single group, whereas the stated planning assumptions refer to equal allocation between two arms. Such assumptions do not turn the single-group trial into a two-arm comparison or supply an observed treatment contrast.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Lonafarnib/Ritonavir")
n   <- c(15)
m   <- c(-1.62)
sp  <- c(1.4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Lonafarnib/Ritonavir  15  -1.620  1.400  -2.395  -0.845

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and a secondary outcome. The primary outcome is change from baseline to Week 24 in mean HDV RNA titer. The secondary outcome is the number of patients with a 1 Log reduction from baseline by timepoint. There are two outcome measures listed and no analysis records. Numerical results for these outcomes are not reported in the registry record.

Multiplicity arises in general when several outcomes, timepoints, or statistical tests are examined, because repeated testing can increase the chance of finding an apparently notable result by chance. A prespecified hierarchy or other adjustment can address some multiplicity concerns. The registry record does not report whether the outcomes were tested under a hierarchy, whether multiplicity adjustments were planned, or how multiple timepoints for the secondary outcome were handled. It is therefore not possible to assess multiplicity control from this record.

Missing-data handling is also not reported in the registry record. The record gives enrollment of 15 but does not state how many participants had baseline and Week 24 measurements, whether any measurements were missing, why they were missing, or how missing values were handled in the analysis. It also does not report whether the analysis used all enrolled participants, participants who received treatment, or participants with observed endpoint measurements. The analysis population is therefore not reported in the registry record.

These omissions matter because the set of participants analyzed and the assumptions used for missing data can influence an estimated mean change. Without those details or the endpoint results, readers cannot assess the possible impact of incomplete follow-up or determine how the primary and secondary outcomes were interpreted together.

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: mandibular fracture) (6.7%).

The registry record lists a safety group of 15 participants receiving lonafarnib/ritonavir. It reports 1 participant affected by a serious adverse event and 15 participants affected by other adverse events. It reports 0 deaths. The top listed serious term is “mandibular fracture)” at 6.7%; the closing parenthesis appears in the term as recorded.

These figures describe participants affected, not necessarily the total number of event episodes. The record does not provide event-level detail, timing, duration, severity beyond the serious classification, or the number of events per participant. It also does not state in the listed safety figures whether events were considered related to treatment. The serious-event count and the count for other adverse events should be read as separate registry categories, not as evidence that every adverse event was serious.

With a group of this size, counts summarize what was recorded among the listed participants but do not by themselves establish the frequency expected in a broader population. The record does not report a comparator group for safety comparison. These figures are descriptive registry data; they do not establish that the regimen caused an event or that an event was unrelated to treatment.

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

The registry record describes a completed phase 2 study in which lonafarnib was titrated with ritonavir in patients chronically infected with HDV. It identifies change in mean HDV RNA titer from baseline to Week 24 as the primary endpoint and reports enrollment of 15. It also records safety counts, including 1 participant affected by a serious adverse event, 15 affected by other adverse events, and 0 deaths.

The record does not report the numerical primary endpoint result. It therefore cannot establish the size or direction of the group’s change in HDV RNA titer, or how precise that estimate was. Nor can it show whether participants had similar changes or substantially different responses, because the endpoint’s standard deviation is identified but not reported. The secondary outcome result is not reported either.

The single-group, open-label design is important to what any result could mean. A before-and-after measurement can describe change among participants receiving the regimen, but without a comparator it cannot isolate the contribution of treatment from other influences on outcomes over time. There is no randomized contrast in the registry record, and masking is listed as none.

The safety counts describe affected participants in the registry’s categories; they do not, by themselves, establish causation or predict risk in other settings. The record does not give the event-level context needed to interpret timing, recurrence, or relationship to treatment.

Overall, the registry record supports a description of the study question, regimen, endpoint, and selected safety counts. It does not provide the outcome statistics needed to assess the primary virologic result. This distinction is important: the absence of a reported result is not evidence that there was no change, and it is not evidence that a change occurred.

14. Why This Trial Matters Statistically

This study is statistically notable as a single-group investigation with a repeated measurement question: how mean HDV RNA titer changed from baseline to Week 24 while participants received a titrating-dose regimen. That design can describe the trajectory of the enrolled group, but it does not provide a randomized comparison. The distinction between describing change and estimating a comparative treatment effect is central to interpreting an endpoint measured before and after treatment.

The primary endpoint is a continuous measure summarized by a mean and standard deviation. Those summaries can communicate the group average and the variation among observations, but the registry record does not report either numerical result. It also does not report an interval estimate or test. The missing result statistics prevent assessment of both magnitude and precision, illustrating why endpoint definitions alone are not enough to evaluate a study’s findings.

The record also illustrates the importance of distinguishing a completed study from a complete results record. Enrollment and completion status provide design context, while analysis populations, missing-data handling, and numerical endpoint findings are needed to judge the evidence. Those details are not reported in the registry record.

Finally, planning assumptions and trial design must be kept separate. The stated planning illustration assumptions refer to equal allocation between two arms, while the study is recorded as single group. Such hypothetical planning calculations cannot be read as the trial’s actual allocation, observed power, or evidence of a comparative effect. Statistical interpretation depends on the design and results actually reported, not on a planning scenario.

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 main limitation for interpretation is that the registry record does not report the primary endpoint estimate or its uncertainty. Although it identifies mean change from baseline to Week 24 and names standard deviation as the dispersion measure, the numerical mean change and standard deviation are not reported. A confidence interval and inferential test result are not reported either. The direction, magnitude, and precision of the primary outcome therefore remain unknown from this record.

The study is listed as single group, open-label, with allocation recorded as NA and masking as none. No comparator group is described. This limits causal interpretation of any within-group change: a change over time cannot by itself show how outcomes would have differed under another treatment or no treatment.

The registry record reports enrollment of 15 but does not report the number assessed at Week 24 or the analysis population. Missing-data frequency, reasons, and handling are not reported in the registry record. These gaps make it impossible to evaluate whether endpoint estimates would be based on all enrolled participants or a subset, and whether incomplete follow-up could affect the result.

The record does not report the statistical plan, the analysis method, multiplicity handling, or any rationale for the sample size. It lists two outcome measures and no analysis records, without numerical outcome results. The dose escalation is described as occurring as tolerated, but the record does not provide participant-level dose exposure or the number reaching each dose.

Safety information is also limited to aggregate counts and a top serious term. Detailed event timing, recurrence, severity beyond the serious category, and relationship to treatment are not reported in the registry record. These limitations restrict what can be concluded from the registry entry; they do not establish that unreported analyses or details were absent from other records.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Titrating-Dose of Lonafarnib in Combination With Ritonavir — NCT02527707.
• Registry record last updated 2026-09-25; status last verified 2023-05.
• Results first posted 2023-06-22.
• 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

NCT02527707 is recorded as a completed phase 2, open-label, single-group study of lonafarnib with ritonavir in patients chronically infected with HDV. Enrollment was 15. The regimen began with lonafarnib 50 mg BID and ritonavir 100 mg BID, with lonafarnib escalating to 75 mg BID and then 100 mg BID as tolerated. The arm description specifies 6 months of treatment and 6 months of follow-up.

The primary endpoint was change from baseline to Week 24 in mean HDV RNA titer, measured in log IU/mL, with standard deviation identified as the dispersion measure. The record also lists a secondary outcome concerning patients with a 1 Log reduction from baseline by timepoint. Numerical results for these outcomes, the statistical analysis, missing-data handling, and analysis population are not reported in the registry record.

The safety record lists 1 participant affected by a serious adverse event, 15 affected by other adverse events, and 0 deaths. The top serious term is recorded as “mandibular fracture)” at 6.7%. The single-group design and absence of reported endpoint results limit interpretation of both efficacy and comparative safety.