Dupilumab for the Treatment of Moderate to Severe Chronic Hepatic Pruritus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dupilumab for the Treatment of Moderate to Severe Chronic Hepatic Pruritus (NCT04256759), a na phase 2 study. The primary outcome is Change in Peak Pruritus Numerical Rating Score (PRNS).

2. Clinical Question

The study asked whether dupilumab might be associated with a change in reported itch severity in this population. Its official title describes it as open-label and exploratory, which is consistent with a study intended to examine a potential treatment signal rather than a randomized comparison. Without a control group, changes over time cannot by themselves distinguish an intervention-associated change from changes that might also occur without the intervention. The registry record does not report a more detailed statement of the primary hypothesis or a formal estimand describing the exact treatment effect being targeted.

3. Trial Design

This was a Phase 2, open-label, single-group study sponsored by Mayo Clinic. The registry record lists enrollment of 9 and status as completed. It records a start date of 2020-09-01 and primary completion on 2024-09-06. These dates describe the registered study timeline; they do not establish when each participant began or completed treatment.

The only intervention arm was dupilumab. The regimen is described as 300 mg by subcutaneous injection every 2 weeks for 18 weeks. Masking is listed as none, and allocation as not applicable. Thus, participants and study personnel were not described as masked, and participants were not allocated between randomized treatment groups. No concurrent control group is listed.

The primary outcome was change in peak PRNS, with baseline and 20 weeks specified as the assessment timeframe. Secondary outcomes listed in the record were change in weekly average peak PRNS of at least 3 from baseline, Verbal Rating Scale score, change in Chronic Liver Disease Questionnaire score, and change in 5D Pruritus Score. The registry record lists 5 outcome measures and 4 analyses, but does not identify the analyses or provide their results.

The record does not report the detailed study protocol, eligibility criteria, recruitment approach, planned sample size, or rationale for enrolling 9 participants. The sample-size assumptions described for planning illustrations are not the trial’s own design assumptions. Since this was a single-arm exploratory study, the interpretation should focus on what the within-group observations can describe, rather than on a treatment-versus-control effect.

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 in Peak Pruritus Numerical Rating Score (PRNS), measured over Baseline; 20 weeks.

The primary endpoint is change in Peak Pruritus Numerical Rating Score (PRNS). The measure asks participants to rate the intensity of their worst itch during the previous 24 hours on a scale from 0 to 10, where 0 means no itch and 10 means the worst itch imaginable. It is a single, self-completed item, assessed before and after treatment. The registry record gives baseline and 20 weeks as the timeframe.

A patient-reported rating can capture a symptom that may not be directly represented by an examination or laboratory measurement. Asking about the peak or worst itch focuses the response on the most intense experience during the stated recall period. In general, repeated scores can be used to describe how participants’ reported symptom severity changes over time. A change score also needs to be interpreted in light of the starting score and the precision of the estimate.

The record identifies the endpoint as a continuous measure summarized by a mean, with standard deviation as the dispersion measure. It describes higher scores as a worse outcome. However, the registry record does not report the baseline or follow-up mean, the mean change, the standard deviation, a confidence interval, or a statistical test for this endpoint. Accordingly, the direction and magnitude of the observed primary outcome cannot be determined from the registered results described in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean represent?

The primary endpoint is identified as a continuous measure summarized by a mean. In general, a mean is an average across participants’ measured values. For a change endpoint, the mean change describes the average of the individual changes, provided the analysis defines and calculates change in that way. It does not show whether every participant changed in the same direction, and it can conceal variation among participants. The registry record does not report the numerical mean or further details of the change calculation.

What does the standard deviation describe?

The listed dispersion measure is the standard deviation. In general, a standard deviation describes how spread out individual observations are around their mean. It is a measure of variability among observations, not a direct measure of uncertainty in the estimated mean. A confidence interval, when reported, addresses uncertainty in an estimate under the analysis assumptions. The registry record does not provide a standard deviation or confidence interval for the primary outcome, so neither participant-level variability nor estimate precision can be assessed from these results.

Why does the single-group design matter?

In general, a before-and-after analysis can describe how observed scores differ across assessment times among the participants measured. It does not estimate a randomized contrast between treatment and control. Without a concurrent comparison group, a change may reflect the intervention, the natural course of symptoms, other events during follow-up, measurement variation, or a combination of influences. These are general interpretive considerations, not claims that any particular influence occurred in this study. The open-label design also means masking is not listed as a protection against knowledge of treatment affecting reporting or assessment.

How should a p-value and confidence interval be read?

In general, a p-value describes how compatible observed data are with a specified statistical model and null hypothesis; it is not the probability that the null hypothesis is true, nor does it measure clinical importance. A confidence interval gives a range of values compatible with the data and analysis method at its stated confidence level. Its width is informative about precision, while its position helps show the direction and plausible magnitude of an estimate. Neither a p-value nor a confidence interval is reported for the primary outcome in the registry record. No statistical test or interval method is identified.

What is over-dispersion?

Over-dispersion is a general issue for some statistical models when the observed variability exceeds what the model assumes. If ignored, uncertainty estimates can be too small and tests can appear more decisive than warranted. This concept is not necessarily applicable to every continuous outcome analysis. The record identifies a continuous mean and standard deviation for the primary measure, but does not report a model, a dispersion assessment, or any adjustment for over-dispersion. It would therefore be inappropriate to assert that over-dispersion was present or addressed.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. That illustration specifies 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 stated fraction of the observed effect. For non-time-to-event illustrations, the stated output is participants per arm for 80% or 90% power; time-to-event illustrations use a total number of events. These are general planning quantities, not observed study findings, and they do not establish the study’s actual power. Because this trial is single-group, an equal-allocation two-arm illustration should not be mistaken for its design. The registry record does not report a trial-specific sample-size justification.

The record lists 4 analyses but does not identify the methods used for them. It also does not report model specifications, covariate adjustment, handling of repeated measurements, or a prespecified analysis plan. Those details should not be inferred from the outcome labels alone.

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("Dupilumab")
n   <- c(9)
m   <- c(-3.1)
sp  <- c(3.9)
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  Dupilumab  9  -3.100  3.900  -6.098  -0.102

11. Multiplicity, Missing Data and Analysis Populations

The record lists 5 outcome measures and 4 analyses. The primary outcome is change in peak PRNS; the listed secondary outcomes include a threshold-based change in weekly average peak PRNS, a Verbal Rating Scale score, change in Chronic Liver Disease Questionnaire score, and change in 5D Pruritus Score. The registry record does not report which analysis corresponds to each outcome, how the 4 analyses were selected, or whether any additional analyses were conducted.

When several outcomes or statistical tests are examined, the chance of at least one apparently notable finding can increase. In general, a prespecified multiplicity strategy may control or otherwise address this issue, but the appropriate approach depends on the analysis plan and the purpose of the outcomes. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or whether the secondary outcomes were intended for confirmatory or exploratory interpretation. Their results should therefore not be treated as independent confirmation of the primary outcome.

The record does not describe missing outcome data, the number of participants contributing data at each assessment, or the reasons for any unavailable measurements. It also does not report an imputation method, sensitivity analysis, or other missing-data procedure. The analysis population is not reported in the registry record: there is no stated rule identifying which enrolled participants were included in each analysis. These omissions limit assessment of whether the outcome estimates, if reported, would represent all enrolled participants or a subset with available measurements.

Although the record states that 9 participants were enrolled, that number alone does not establish how many had an evaluable primary endpoint at the stated follow-up. No assumptions about completeness or participant-level analysis can be made from enrollment alone.

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 0% reporting threshold.

The registry record lists 9 participants at risk for serious adverse events and 0 participants affected by a serious adverse event in the Dupilumab group. It lists 9 participants at risk for other adverse events and 0 affected by other adverse events. Deaths are listed as 0. These are event-count summaries for the group and risk sets identified in the record.

Zero affected participants in a small study group is not proof that an event cannot occur, nor does it establish the absence of risk in a broader population. In general, safety counts depend on the number of participants observed, the duration and completeness of follow-up, and how events are defined, collected, and reported. The record does not provide detailed follow-up time, event definitions, collection procedures, or participant-level safety information. No serious adverse-event terms are listed.

These figures should be read as registry-reported counts, not as a comparison of safety between treatments. The study had no control arm, and the safety figures do not establish whether events were caused by treatment. They also do not substitute for a comprehensive assessment of all possible adverse effects.

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

The registry record describes an exploratory investigation of dupilumab in moderate to severe chronic hepatic pruritus, with change in peak PRNS as the primary outcome. It establishes that the study was open-label and single-arm, enrolled 9 participants, and assessed the primary measure at baseline and 20 weeks. It also records a subcutaneous regimen of 300 mg every 2 weeks for 18 weeks and reports no affected participants in the listed serious or other adverse-event categories, with 0 deaths.

Those design and safety details do not supply the primary efficacy result. The registry record does not report the observed PRNS values or change, or an estimate of precision. As a result, the magnitude and direction of any change cannot be characterized. The absence of a concurrent control also means that any within-group change, if available, could not alone determine what portion was attributable to treatment rather than other influences over time.

In general, a confidence interval would help convey how precisely an estimated change was measured, while a control group would support a comparative treatment-effect estimate. Neither a primary-outcome confidence interval nor a controlled comparison is reported for this study. The record also does not provide enough detail to assess missing outcome data, the analysis population, or how multiple outcomes were handled.

Accordingly, the registered information supports a description of the study question, design, endpoints, and reported safety counts, but not a conclusion about the size or precision of a change in itch severity. It also does not establish that the results apply to people beyond the participants enrolled. These boundaries are important when interpreting an exploratory study with a small enrollment and no comparator.

14. Why This Trial Matters Statistically

This study illustrates a basic distinction between describing change and estimating a comparative effect. A single-group study can be structured to observe scores before and after treatment, but it does not include a concurrent control group to show how outcomes might have changed over the same period without the intervention. That design feature affects the meaning of any within-group result, irrespective of whether a change appears large or small.

The endpoint is a self-completed symptom rating with a defined recall period and scale. In general, patient-reported measures can directly represent a participant’s experience, but interpretation also depends on consistency of measurement, completeness of follow-up, and transparent reporting of the analysis. Here, the registry identifies the measure and timeframe, while the outcome values and analysis details are not reported in the registry record.

The enrollment of 9 is also statistically important. In general, limited numbers of observations can make estimates less precise and leave substantial uncertainty about how well findings represent a wider population. Precision cannot be judged from enrollment alone; it ordinarily requires outcome estimates and measures of uncertainty, which are not reported for the primary endpoint.

The record additionally lists several secondary measures and a planning illustration. Keeping those distinct from the primary analysis matters: multiple outcomes can raise interpretive questions, while a planning illustration based on an observed effect is not evidence of observed power or a trial-specific design justification. Overall, this record is useful for understanding the study’s exploratory structure and what it intended to measure, while highlighting why complete outcome and analysis reporting is needed for statistical interpretation.

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 most direct limitation for interpreting results is that the registry record does not report numerical primary outcome results. Without baseline and follow-up values, a change estimate, or an uncertainty measure, the primary endpoint cannot be quantitatively evaluated. The record also does not provide numerical results for the listed secondary outcomes.

The single-arm design has no concurrent comparator, and the study is described as open-label with no masking. General limitations of this structure include difficulty separating changes associated with treatment from other influences over time, and the possibility that knowledge of treatment may affect a self-reported measure. These are design considerations, not evidence that a specific bias occurred.

The enrollment of 9 restricts the amount of information available from the study. The registry record does not report baseline participant characteristics, the number with measurements at each time point, or details of follow-up. As a result, it is not possible to assess the representativeness of the enrolled group or the completeness of outcome measurement. Eligibility criteria and the analysis population are also not reported in the registry record.

Further limitations concern the analysis description. The record lists 4 analyses but does not describe their methods, identify a statistical analysis plan, explain missing-data handling, or state how multiple outcomes were addressed. It does not report the trial’s sample-size justification or interim analyses. The planning assumptions are described as an illustration rather than the trial’s own design. These gaps prevent assessment of whether the analyses followed a prespecified plan and how robust any findings would be to alternative analytic choices.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dupilumab for the Treatment of Moderate to Severe Chronic Hepatic Pruritus — NCT04256759.
• Registry record last updated 2025-11-21; status last verified 2025-11.
• Results first posted 2025-11-21.
• 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

The registry record describes a completed Phase 2, open-label, single-arm exploratory study of dupilumab for moderate to severe chronic hepatic pruritus. Mayo Clinic is listed as sponsor, and enrollment is 9. The intervention is subcutaneous dupilumab at 300 mg every 2 weeks for 18 weeks. The primary outcome is change in peak PRNS, assessed at baseline and 20 weeks.

Secondary outcomes include a threshold-based weekly average peak PRNS measure, Verbal Rating Scale score, Chronic Liver Disease Questionnaire score, and 5D Pruritus Score. The record lists 5 outcome measures and 4 analyses but does not report the primary outcome values, analysis details, or missing-data procedures. It reports 0 participants affected by serious adverse events, 0 affected by other adverse events, and 0 deaths among the listed group summaries. The single-group design does not support a concurrent treatment comparison.