A Study to Evaluate the Mechanism of Action of Ruxolitinib Cream in Subjects With Vitiligo (TRuE-V MOA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Mechanism of Action of Ruxolitinib Cream in Subjects With Vitiligo (TRuE-V MOA) (NCT04896385), a randomized phase 2 study. The primary outcome is Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24.

2. Clinical Question

The study was designed to examine a mechanism of action by assessing changes in biomarkers in people with vitiligo. CXCL10 was the primary biomarker endpoint. The record also names correlation of key skin inflammatory biomarkers in target lesions to efficacy readouts as a secondary outcome, but it does not report the correlation results.

This is a biomarker question, not a direct estimate of how much vitiligo changed clinically. Although the registry lists other secondary outcomes, including treatment-emergent adverse events, the primary endpoint focuses on percentage change in CXCL10. The registry record does not report a numerical primary treatment effect, its uncertainty, or a statistical test result. Consequently, it cannot establish from the posted results whether the biomarker differed between treatment groups at any of the listed visits.

3. Trial Design

This was a phase 2 randomized, triple-masked, vehicle-controlled crossover study in people with vitiligo. The study enrolled 60 participants and is recorded as completed. The registry lists a start date of 2021-06-23 and a primary completion date of 2022-11-17. In a crossover design, participants receive treatments in different periods rather than remaining in a single treatment group throughout; however, the treatment sequence, period details, and any washout arrangements are not reported in the registry record.

The active intervention was ruxolitinib cream, described as 1.5% and applied twice a day for 24 weeks. The comparator was vehicle cream, which was described as matching the active cream in appearance and being applied in the same manner. Randomization assigns treatment according to a chance-based process, helping limit systematic differences in treatment assignment. Masking is intended to reduce the influence of treatment knowledge on care, measurement, and assessment. The record labels masking as triple but does not identify which roles were masked.

The primary endpoint was mean percentage change from baseline in CXCL10 at Week 4, Week 12, and Week 24. Baseline was the last non-missing measurement obtained on or before the first application of study drug. The primary endpoint population was the safety population: participants who applied at least one dose. Treatment groups for this population were determined according to the actual treatment received on Day 1, and only participants with available data were analyzed.

The crossover label does not by itself explain how the analysis accounted for treatment period, sequence, or possible carryover. Those details, the allocation ratio, and the statistical analysis plan are not reported in the registry record. The record describes the study as evaluating biomarker changes and lists secondary biomarker and safety outcomes. It does not provide numerical primary endpoint results in the information available for this analysis.

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: This study was conducted at a total of 11 sites in Canada, France, and the United States.

24-Week Double-Blind Period

Reasons for not completing this period:

28-Week Treatment-Extension Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population: all participants who applied at least 1 dose of study drug. Treatment groups for this population were to be determined according to the actual treatment the participant received on Day 1. Only participants with available data 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 Percentage Change From Baseline in Chemokine (C-X-C Motif) Ligand 10 (CXCL10), an Immune Biomarker, at Week 4, Week 12, and Week 24, measured over Baseline; Week 4, Week 12, and Week 24.

The primary endpoint measures percentage change from baseline in CXCL10, an immune biomarker, at Week 4, Week 12, and Week 24. The registry defines the calculation as the post-baseline value minus the baseline value, divided by the baseline value, and multiplied by 100. This expresses change relative to each participant’s baseline measurement rather than as an absolute change in the biomarker’s measurement units.

Baseline was defined as the last non-missing measurement on or before the first application of study drug. This rule anchors the change calculation to a measurement taken before treatment began, according to the registry definition. The endpoint is summarized as a mean, with standard deviation as the measure of dispersion. A mean describes the average observed change; a standard deviation describes how spread out participant-level changes are around that average.

CXCL10 was selected as an immune biomarker in a study whose stated purpose was to evaluate the mechanism of action of ruxolitinib cream in vitiligo by assessing biomarker changes. Biomarkers can help characterize biological processes, but a change in a biomarker is not by itself a direct measure of clinical improvement. The registry record does not report the mean changes, standard deviations, treatment comparisons, confidence intervals, or p-values for the primary endpoint. Therefore, the endpoint’s numerical findings and their precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous measure: percentage change from baseline in CXCL10. The registry specifies a mean and standard deviation. In general, a mean is useful for describing the average participant-level change, while the standard deviation describes variation among participant-level changes. They answer different questions: the mean concerns the central average, and the standard deviation concerns spread. Neither is a substitute for a treatment contrast or an estimate of its uncertainty.

What does percentage change represent?

The calculation compares a post-baseline measurement with the baseline measurement, scales that difference relative to baseline, and expresses it as a percentage. This makes the change relative to the starting value. As a general statistical consideration, percentage change can be sensitive to the baseline value: when baseline measurements vary, the same absolute change can correspond to different percentage changes. The registry record gives the formula and baseline rule but does not report participant-level measurements or numerical endpoint summaries.

The baseline measurement was defined as the last non-missing value on or before the first application of study drug. A consistent baseline rule is important because it establishes which pre-treatment value anchors each participant’s change. The record says that only participants with available data were analyzed for the primary endpoint. It does not report the number with endpoint data at each visit or describe how missing measurements were handled beyond that available-data statement.

How should a crossover design be understood?

In a crossover study, participants receive treatments in separate periods, so comparisons may draw on measurements from the same participant under different treatments. In general, within-participant comparisons can account for stable characteristics that might otherwise differ between groups. They also require attention to period effects, treatment sequence, and possible carryover from an earlier treatment period. These design features affect which model is appropriate and how treatment effects should be interpreted. The registry record labels this study crossover but does not report the sequence, period schedule, washout details, or analysis model used to address these considerations.

Randomization and masking serve different purposes. Randomization is intended to reduce systematic differences in treatment assignment. Masking can reduce the chance that knowledge of treatment influences participant behavior, outcome assessment, or other study processes. The record identifies randomization and triple masking, but does not describe the allocation procedure or identify the roles that were masked. Those operational details are not reported in the registry record.

What would quantify uncertainty?

A treatment comparison would ordinarily be interpreted alongside an uncertainty measure, such as a confidence interval. In general, a confidence interval conveys the range of effect estimates compatible with the data under the chosen method and its assumptions. A narrow interval indicates greater precision than a wide interval, but precision does not establish clinical importance. The registry record does not report confidence intervals for CXCL10, nor does it report the treatment effect estimates or standard deviations needed to describe the primary endpoint numerically.

A hypothesis test may also be used to assess compatibility between the data and a specified null hypothesis. In general, a p-value is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. The statistical plan, hypothesis tests, and p-values for the primary endpoint are not reported in the registry record. The absence of those details means the posted record does not allow readers to check the inferential approach or reproduce the primary analysis.

Why do multiple visits matter?

Assessing the same endpoint at Week 4, Week 12, and Week 24 creates multiple opportunities to examine change. In general, conducting several tests can increase the chance of a false-positive finding if each is interpreted independently without accounting for multiplicity. Possible approaches include specifying a primary visit, adjusting the significance threshold, or using a model that estimates the pattern across visits. These are general methods, not statements about the approach used in this study. The registry record does not report a multiplicity strategy or identify a single treatment contrast for the primary endpoint.

The record indicates that the primary outcome has several time points and was not reduced to one comparison. That makes it especially important to distinguish a visit-specific result from an overall treatment effect. It also means that a single summary number would not fully describe the endpoint unless its definition and analysis were stated. Those details and the numerical findings are not reported in the registry record.

What can planning calculations tell readers?

Sample-size calculations are planning illustrations, not observed power. The stated assumptions describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is framed as a stated fraction of the observed effect. Such calculations depend on their assumptions and are not a measure of how likely the completed study was to detect an effect. The primary endpoint has multiple time points and is not reduced to one comparison, so the record does not identify a single primary contrast for interpreting such planning figures. Planning illustrations should not be read as additional clinical findings.

For other endpoints, the registry lists secondary biomarker and safety outcomes. Correlation analyses answer a different question from a randomized treatment contrast: in general, correlation describes the degree to which two measures vary together, not whether one causes the other. The registry record does not report numerical correlation estimates or the methods used for those analyses. Overall, the available information identifies several design and endpoint features but does not provide the analysis details or primary results needed for a full statistical appraisal.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is assessed at Week 4, Week 12, and Week 24. Considering multiple visits raises a general multiplicity issue: if each visit is tested separately, interpreting all tests without adjustment can increase the chance of at least one false-positive result. A prespecified approach could define a main visit, adjust for multiple testing, or model the measurements across visits. The registry record does not report which approach, if any, was used. It also does not report a single primary treatment comparison for the endpoint.

The primary endpoint population is the safety population, defined as participants who applied at least one dose of study drug. Treatment groups for that population were assigned according to actual treatment received on Day 1. Only participants with available data were analyzed. These definitions indicate who could contribute to the endpoint, but the record does not report how many participants had CXCL10 measurements at each visit or whether the analyzed set changed across visits.

Missing-data handling beyond analyzing participants with available data is not reported in the registry record. In general, an available-data analysis can be affected if the likelihood of having a measurement is related to the participant’s outcome or treatment experience. Without the amount, timing, and reasons for missingness, readers cannot assess that possibility or determine whether imputation or sensitivity analyses were used.

The registry record also does not report the statistical analysis plan, any interim analyses, or detailed methods for handling crossover periods and treatment sequence. Those omissions limit assessment of whether the analysis followed prespecified decisions and how uncertainty was handled. Numerical primary outcome results, including estimates and their precision, are not reported in the registry record.

11. 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: acute coronary syndrome (1.8%).

The serious adverse event counts are reported with the number of participants at risk in each treatment group. In the Ruxolitinib Cream 1.5% BID group, 1 of 55 participants was affected by a serious adverse event; in the Vehicle Cream BID group, 0 of 19 were affected. These are observed counts for the periods represented in the registry record, not estimates of comparative risk adjusted for differences in exposure or study design. No deaths were reported in either group.

The registry lists Acute coronary syndrome as a serious adverse event term, with 1.8% recorded. The record does not provide enough detail to assign that term to a treatment group or describe its clinical course. Serious events are distinct from the broader category of other treatment-emergent adverse events: the record reports 10 of 55 participants in the ruxolitinib group and 7 of 19 in the vehicle group for that category. These counts should not be added together or treated as a count of all events, because the reported measure is participants affected and a participant may experience more than one event.

Differences in the observed counts do not establish that one treatment caused more or fewer events. The groups differ in the number at risk, and the registry record does not report a comparative statistical analysis of safety. These findings describe the posted safety data; they do not establish the safety profile beyond the study.

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

The study addresses a biological question: whether ruxolitinib cream is associated with changes in CXCL10, an immune biomarker, in people with vitiligo. The registry identifies the endpoint, the baseline definition, and the assessment visits. It also provides some safety counts. However, it does not report the numerical CXCL10 results or a treatment comparison. The available record therefore cannot quantify the biomarker change or its precision.

A biomarker endpoint can inform understanding of biological activity, but it is not automatically equivalent to a clinical outcome. The study also lists a secondary outcome concerning correlation of inflammatory biomarkers in target lesions to efficacy readouts. The correlation results are not reported in the registry record. Without those data, the record does not show how biomarker changes related to clinical efficacy measures.

The study’s randomized, masked, vehicle-controlled design can support a structured comparison, but design labels alone do not establish the result. Interpretation also depends on the analysis population, available measurements, treatment periods, and statistical methods. The record defines the safety population for the primary endpoint and says only participants with available data were analyzed, but details of missingness and the analysis model are not reported.

The safety counts describe events recorded during study periods and should be read as descriptive observations. They do not, by themselves, prove a causal relationship or provide a precise comparison between treatments. Likewise, a planning illustration based on an observed effect is not observed power and does not replace the results of the completed study.

Accordingly, the registry record establishes what the study set out to measure and reports selected safety counts, but it does not provide enough primary endpoint results to determine the size or direction of a CXCL10 treatment difference. It also cannot, on the available information, establish a clinical benefit or lack of benefit. Those conclusions would require numerical outcome results and details of their statistical analysis, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable because it combines a biomarker endpoint with a randomized, triple-masked crossover design. Biomarker studies can help characterize biological processes, while a controlled design can help separate treatment-associated changes from changes that might occur without the active cream. A crossover structure introduces its own analytical questions, including treatment sequence, period effects, and possible carryover. The registry identifies the design but does not report how those questions were handled.

The primary endpoint is measured at multiple visits rather than at a single time point. That matters because estimates may differ across visits, and multiple assessments require a clear approach to multiplicity and interpretation. The registry record says the primary outcome has several time points and is not reduced to one comparison. It does not report a strategy for interpreting the visit-specific results or a numerical effect estimate at any visit.

The endpoint also illustrates the distinction between a biomarker and a clinical outcome. CXCL10 is an immune biomarker, and the study’s stated purpose is to assess biomarker changes related to mechanism of action. A biomarker result may be informative about biological processes, but its meaning for clinical efficacy depends on evidence connecting it to relevant clinical outcomes. The record lists a correlation outcome but does not report its results.

Finally, the registry record shows why design descriptions and outcome definitions are not a substitute for results. It identifies the population, treatment approach, comparator, baseline rule, and assessment schedule, yet the numerical primary findings and inferential methods are not reported. That distinction is important when evaluating what can be concluded from a trial record: the research question is clear, but the key data needed to quantify the primary comparison are absent from the posted information.

14. 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 numerical results for the primary CXCL10 endpoint. Means, standard deviations, treatment comparisons, confidence intervals, and p-values are not reported. Without these, the magnitude, direction, and precision of the primary findings cannot be assessed.

The endpoint is evaluated at Week 4, Week 12, and Week 24, but the registry record does not identify a single primary comparison or report how multiplicity was addressed. It also does not report whether results were modeled across visits or estimated separately. As a result, the relationship among the time-specific assessments cannot be evaluated.

The record labels the design crossover, but treatment sequence, period details, washout arrangements, and the statistical approach to period or carryover effects are not reported. These omissions prevent assessment of whether the analysis reflects the design’s key features. The allocation ratio and the roles included in triple masking are also not reported in the registry record.

For the primary endpoint, the analysis included participants with available data in the safety population, but the number with data at each visit, reasons for missingness, and any imputation or sensitivity analyses are not reported. The record lists secondary biomarker and safety outcomes, but does not report the correlation results or a detailed statistical plan. The safety counts are descriptive and do not include a reported comparative analysis. These limitations apply to interpretation of the posted registry information; they do not establish whether further analyses were conducted elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Mechanism of Action of Ruxolitinib Cream in Subjects With Vitiligo (TRuE-V MOA) — NCT04896385.
• Registry record last updated 2025-08-05; status last verified 2025-08.
• Results first posted 2023-12-07.
• 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.

18. Record Summary

The registry record describes NCT04896385, a completed phase 2 randomized, triple-masked, vehicle-controlled crossover study of ruxolitinib cream in vitiligo. It enrolled 60 participants. Ruxolitinib cream was described as 1.5% and applied twice a day for 24 weeks; the vehicle cream matched its appearance and was applied in the same manner.

The primary endpoint was mean percentage change from baseline in CXCL10 at Week 4, Week 12, and Week 24, with standard deviation as the measure of dispersion. The primary analysis population was the safety population, and only participants with available data were analyzed. Numerical results for the primary endpoint and its statistical comparison are not reported in the registry record.

The record reports serious adverse events in 1 of 55 participants in the ruxolitinib group and 0 of 19 in the vehicle group, with no deaths in either group. It also lists other treatment-emergent adverse events and a serious adverse event term. The statistical analysis plan, detailed crossover analysis methods, missing-data methods, and numerical biomarker correlation results are not reported in the registry record.