Vidofludimus Calcium for Primary Sclerosing Cholangitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vidofludimus Calcium for Primary Sclerosing Cholangitis (NCT03722576), a na phase 2 study. The primary outcome is Subjects Who Experience a Positive Outcome as Measured by Combination of Serum Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) Levels..

2. Clinical Question

3. Trial Design

This is a phase 2 study of vidofludimus calcium in people with primary sclerosing cholangitis. The registry describes a single-group design, daily dosing over 6 months, and an enrollment of 18. Allocation is recorded as NA, and masking as none. No control group or randomized treatment comparison is described.

The study began on 2019-06-17, had a primary completion date of 2020-06-30, and is listed as completed. Those dates describe the registry record; they do not provide participant-level follow-up or establish how long each participant remained in the study.

The primary endpoint timeframe is baseline to 24 weeks. It is a participant count based on meeting a joint ALP and AST criterion. The registry says that only participants who completed treatment were analyzed. The number completing treatment, the number included in the endpoint analysis, and the primary endpoint count are not reported in the registry record.

Four secondary outcomes are listed: abnormal AST, abnormal ALT, abnormal total bilirubin, and abnormal direct bilirubin. The record lists five outcome measures in total, but does not report analysis results for them. The study description identifies safety, tolerability, and efficacy as its aims; the registry record does not provide further detail about how those aims were translated into a complete statistical analysis 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:

Analysis population for the primary outcome, as defined in the registry: Only subjects who completed treatment were analyzed

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 Subjects Who Experience a Positive Outcome as Measured by Combination of Serum Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) Levels., measured over Baseline to 24 weeks.

The primary endpoint counts participants meeting a combined laboratory criterion between baseline and 24 weeks. A participant qualifies only if both conditions are met: ALP falls from baseline by at least 25%, and AST rises from baseline by no more than 33%. The endpoint uses ALP and AST measured in international units per liter.

This is a joint endpoint: meeting just one of the two conditions is not enough to count as a positive outcome under the stated definition. Reporting a count can make the endpoint straightforward to interpret as the number of participants meeting the prespecified criterion. However, interpretation also depends on knowing how many participants were analyzed and how missing measurements or incomplete treatment were handled. Those details are not reported in the registry record.

As a general statistical point, combining measures can capture more than one aspect of a laboratory response, but it can also make the result dependent on the exact thresholds and on both components being available. The endpoint definition gives those thresholds, while the observed count and its uncertainty are not reported in the registry record. The endpoint is therefore defined, but its result cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a count of participants who meet a binary criterion. Each participant either meets the combined ALP and AST definition or does not, based on measurements from baseline to 24 weeks. The criterion requires both an ALP reduction of at least 25% and an AST increase no greater than 33%. The posted record does not give the observed count or its analysis denominator.

What does a participant count tell us?

A count is a direct summary of how many people met an outcome definition. For interpretation, a count is usually considered alongside the number of people assessed. The denominator matters because the same count can have a different meaning in groups of different sizes. Here, the registry reports enrollment of 18, but the primary analysis was restricted to participants who completed treatment. The number completing treatment and the number analyzed are not reported in the registry record, so enrollment cannot be assumed to be the endpoint denominator.

As a general statistical concept, estimates based on a limited number of participants can be imprecise. A confidence interval expresses a range of values compatible with the data under the assumptions of the method used. The registry record does not report a confidence interval or another uncertainty estimate for the primary endpoint. Without the endpoint count, denominator, and uncertainty estimate, the precision of the primary result cannot be evaluated.

Why does the single-group design matter?

In a single-group study, outcomes are observed among participants receiving the study intervention, without a concurrent comparator group. A before-and-after endpoint can describe the observed change from baseline, but it cannot alone establish what would have happened over the same period without the intervention. General sources of change over time, including natural variation in measurements, are not separated from intervention-associated change by a single-group contrast.

The registry records no masking and no allocation to a comparator. Accordingly, there is no randomized between-group estimate to interpret. Statistical methods designed to compare randomized groups should not be treated as if they were the analysis used for this study. The registry record does not report an adjusted model, a covariate strategy, or another inferential method for the primary endpoint.

How should the endpoint thresholds be understood?

The primary outcome is not simply an ALP result or an AST result. It combines two change criteria, and a participant must satisfy both to meet the stated endpoint. This construction makes the endpoint sensitive to measurements for both laboratory tests and to the exact thresholds selected. As a general point, binary thresholds simplify a result into meeting versus not meeting a definition, but they do not show the full distribution of underlying measurements. The registry does not report those distributions or the separate component results for the primary endpoint.

The endpoint timeframe is baseline to 24 weeks, while the intervention description states daily dosing over 6 months. The record does not explain any distinction between these descriptions or report measurement schedules beyond the endpoint timeframe. It also does not report how measurements outside the specified visit, if any, were handled.

What can the planning illustrations establish?

The planning illustrations are described as calculations based on an observed effect, rather than the trial’s own design. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. These are planning assumptions, not evidence that this single-group study used a two-arm design. The registry record does not report the trial’s sample-size justification, and no planning illustration should be interpreted as observed power or as a result from the study.

As a general statistical distinction, a sample-size calculation asks how many participants might be needed under specified assumptions for a future comparison. It does not establish the probability that a completed study has demonstrated an effect. In particular, a calculation based on an observed effect can depend on that effect estimate, and the registry does not report the primary outcome count needed to assess such an estimate independently.

Why does over-dispersion matter in general?

Over-dispersion is a general concern when count data vary more than a chosen statistical model expects. If a model assumes less variability than the data contain, standard errors may be too small and uncertainty may appear narrower than warranted. The registry describes this primary endpoint as a binary participant count, but does not report a model-based analysis or any assessment of over-dispersion. This concept therefore explains a general modeling issue; it is not a reported finding about this study.

Finally, inferential statistics depend on the analysis population, outcome definition, handling of incomplete data, and method used to quantify uncertainty. Several of these details are not reported in the registry record. The posted material supports a description of the endpoint and design, but not a reconstruction of unreported analyses.

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("Vidofludimus Calcium (VC)")
n      <- c(11)
events <- c(3)
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  Vidofludimus Calcium (VC)  11  3  27.3  6.0  61.0  9.7  56.6  9.9  57.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures: the primary combined ALP and AST endpoint and four secondary outcomes concerning abnormal AST, abnormal ALT, abnormal total bilirubin, and abnormal direct bilirubin. It lists no analyses. The result values for these outcomes and any testing strategy are not reported in the registry record.

Multiplicity is a general statistical issue that arises when several outcomes or hypotheses are assessed. Testing multiple outcomes can increase the chance of at least one apparently unusual result if each is considered separately. Researchers may address this through a prespecified hierarchy, an adjustment, or a clear distinction between confirmatory and exploratory analyses. The registry record does not report whether any such approach was planned or used. It is therefore not possible to determine how the secondary outcomes were intended to relate to the primary endpoint or how their inference should be interpreted.

Missing-data information is also limited. The primary analysis included only participants who completed treatment, but the number of completers, reasons for noncompletion, and handling of missing laboratory measurements are not reported in the registry record. A completer-only analysis can describe the participants with completed treatment, but if completion is related to outcome or tolerability, its results may not represent all enrolled participants. This is a general limitation, not a claim about why any participant did or did not complete treatment.

The record does not report whether an intention-to-treat population, a per-protocol population, or another analysis population was defined. It also does not report imputation methods, sensitivity analyses, or procedures for measurements that were unavailable at the endpoint. Consequently, the impact of missing information and the robustness of any outcome analysis cannot be assessed from the posted results.

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.

Most frequent non-serious adverse event terms

The registry lists 18 participants at risk for serious adverse events, with 0 affected, and 0 deaths. It lists no serious adverse event terms. It also records 18 participants at risk for other adverse events, with 12 affected. These are the safety counts reported in the registry; the record does not provide event-level descriptions for the other adverse events.

As a general statistical point, a count of zero observed events does not prove that an event is impossible or that risk is absent. The meaning of a safety count depends on the number followed, the length and completeness of observation, and the definitions used for event categories. The registry record does not report enough detail to characterize those factors beyond the stated at-risk counts.

Seriousness is a specific adverse-event classification and should not be confused with severity or with the total number of other adverse events. The 0 serious adverse events and 0 deaths should therefore be read as recorded counts, not as a comprehensive characterization of all safety outcomes. The count of 12 participants with other adverse events does not, by itself, indicate their nature, seriousness, or relationship to treatment.

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

The registry record establishes that a phase 2, single-group study of daily vidofludimus calcium was conducted in primary sclerosing cholangitis, with enrollment of 18 and treatment described over 6 months. It also defines a primary outcome based on meeting both an ALP reduction threshold and an AST increase threshold from baseline to 24 weeks. These details explain what the study set out to examine.

The record does not report how many participants met the primary endpoint. It also does not report the endpoint analysis denominator, uncertainty around the result, or values for the listed secondary outcomes. Therefore, the posted results do not show whether or how often participants met the laboratory criterion, nor how precisely any observed effect was estimated.

The single-group design cannot provide a randomized comparison with an untreated or alternative-treatment group. As a general statistical point, observations during treatment may describe what happened to participants in the study, but without a comparator they cannot by themselves isolate the effect of treatment from other explanations for change. The registry record also does not report a statistical analysis that would address this limitation.

The safety information reports 0 participants with serious adverse events among 18 at risk, 0 deaths, and 12 participants with other adverse events among 18 at risk. These counts are limited to the recorded categories and do not establish comparative safety. The registry does not report the specific terms for the other adverse events or details needed to characterize them fully.

Accordingly, this record supports a description of the trial’s design, endpoint, and listed safety counts, but not a conclusion about efficacy or comparative safety. Absence of a reported primary result is not evidence that the endpoint was or was not met. A fuller interpretation would require the outcome counts, analysis population, missing-data information, and statistical estimates, none of which are reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a clearly defined endpoint and a reported endpoint result are both necessary. The primary outcome specifies a joint criterion using ALP and AST, a baseline reference, and a 24-week timeframe. That definition makes the intended measurement understandable, but without the count meeting the criterion and its denominator, readers cannot assess the observed result.

The single-group design also illustrates the distinction between describing change and estimating a comparative treatment effect. A within-participant change may be clinically and statistically interesting, but the design has no concurrent comparator to show how outcomes would have differed under another condition. This limits the claims that can be supported, regardless of the endpoint definition.

Another statistical lesson concerns analysis populations. The registry states that only participants who completed treatment were analyzed for the primary endpoint. Without the number of completers or information about missing measurements, the endpoint’s coverage and potential sensitivity to incomplete follow-up remain unclear. These details are important for judging both the reliability and generalizability of an estimate.

Finally, the record lists several secondary laboratory outcomes but no analyses. When multiple outcomes are assessed, readers need to know which analyses were planned and how findings were intended to be interpreted. That information is not reported. The study therefore highlights how transparent reporting of estimates, uncertainty, analysis populations, missing-data procedures, and multiplicity plans is necessary to move from a protocol-level question to an interpretable statistical result.

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 important trial-specific limitation in the registry record is that the primary endpoint result is not reported. The number of participants meeting the combined ALP and AST criterion is absent, as are the endpoint analysis denominator and any estimate of uncertainty. The four listed secondary outcomes also have no reported result values.

The primary analysis is described as including only participants who completed treatment, but the number completing treatment is not reported in the registry record. Reasons for noncompletion and methods for handling missing laboratory measurements are also not reported. This prevents assessment of whether the analyzed participants may differ from those enrolled in ways relevant to the endpoint.

The study is single group, with no comparator and no masking. These design features limit comparative interpretation. The registry does not report an adjusted analysis or another method for accounting for changes that might have occurred over time independently of treatment.

The record lists safety counts but provides limited event detail. It reports no serious adverse event terms and does not describe the types, timing, or severity of the 12 participants’ other adverse events. The posted information therefore supports only a limited descriptive reading of safety.

Finally, the registry does not report a sample-size justification, a statistical analysis plan, a multiplicity strategy, or missing-data sensitivity analyses. The planning assumptions described for illustrative sample-size calculations should not be mistaken for the study’s own design rationale. These omissions restrict how fully the study’s findings and precision can be evaluated.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Vidofludimus Calcium for Primary Sclerosing Cholangitis — NCT03722576.
• Registry record last updated 2022-10-17; status last verified 2022-10.
• Results first posted 2021-06-02.
• 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

NCT03722576 is a completed phase 2, single-group study of vidofludimus calcium for primary sclerosing cholangitis. The registry lists enrollment of 18, daily dosing over 6 months, and no masking. The primary endpoint counts participants who, from baseline to 24 weeks, had an ALP reduction of at least 25% and an AST increase no greater than 33%; only participants who completed treatment were analyzed.

The primary endpoint count and results for the four listed secondary laboratory outcomes are not reported in the registry record. The safety record lists 0 serious adverse events among 18 at risk, 0 deaths, and 12 participants with other adverse events among 18 at risk. The single-group design provides no randomized comparator, and the posted results do not permit assessment of the primary endpoint’s magnitude or precision.