A Trial to Assess the Effect of Delgocitinib Cream 20 mg/g on the Molecular Signature, Safety, and Efficacy in Adults With Frontal Fibrosing Alopecia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Assess the Effect of Delgocitinib Cream 20 mg/g on the Molecular Signature, Safety, and Efficacy in Adults With Frontal Fibrosing Alopecia (NCT05332366), a randomized phase 2 study. The primary outcome is Change in Expression of Chemokine (C-X-C Motif) Ligand 9 (CXCL9), Chemokine (C-X-C Motif) Ligand 10 (CXCL10), and Interferon (IFN)-γ From Baseline to Week 12..

2. Clinical Question

3. Trial Design

This was a Phase 2a randomized, double-blind, vehicle-controlled, parallel-group exploratory trial at a single site. The registry lists enrollment of 35 and a completed status. The recorded study start was 2022-04-19, and primary completion was 2023-02-13. These dates describe the registry record and do not by themselves establish when each participant began or completed treatment.

During the first 12 weeks, participants were randomized under blinded conditions to delgocitinib cream or its vehicle. The arm descriptions then specify an open-label period lasting another 12 weeks, during which participants in both arms received delgocitinib cream. Consequently, the blinded vehicle-controlled comparison addresses the initial treatment period; the later period does not retain the same randomized vehicle comparison because both described treatment arms receive delgocitinib.

A no-treatment group was included to provide a molecular signature of healthy skin as a control. The registry states that this group did not receive treatment and that no primary outcome data were collected for it. It should therefore not be interpreted as a third randomized treatment arm in the delgocitinib-versus-vehicle comparison.

The registry record does not report the randomization procedure, allocation concealment details, the number of sites beyond identifying the trial as single-site, or the rationale for the enrollment target. It identifies double masking but does not describe which study roles were masked or how masking was maintained. Those details should not be inferred from the design labels alone.

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: Eligible subjects were randomized into the trial after a screening period. They were assigned to receive either delgocitinib cream or a placebo twice daily for 12 weeks. After completing this period, they continued using delgocitinib cream for another 12 weeks.

Overall Study

Analysis population for the primary outcome, as defined in the registry: No data was collected for "No Treatment" Arm/Groups".

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 Expression of Chemokine (C-X-C Motif) Ligand 9 (CXCL9), Chemokine (C-X-C Motif) Ligand 10 (CXCL10), and Interferon (IFN)-γ From Baseline to Week 12., measured over Baseline and Week 12.

The primary endpoint was change in expression of CXCL9, CXCL10, and interferon-γ (IFN-γ) from baseline to Week 12, reported in fold-changes. The registry describes these as small proteins that act as chemical messengers, especially in the immune system. The endpoint was intended to characterize the molecular signature of FFA and assess whether delgocitinib was associated with a change in that signature in active lesions.

As general context, molecular measures can capture biological activity that may not be directly represented by a clinical assessment. A baseline-to-follow-up change also gives a way to describe how a marker varies during the study period. However, a change in a molecular marker is not by itself a direct measure of how a participant feels or functions, and it does not establish a clinical benefit. That requires interpretation alongside relevant clinical outcomes and the design of the comparison.

The registry record does not post the observed fold-changes, group-level estimates, uncertainty intervals, or a statistical comparison for these markers. It also does not report how the three markers were combined or whether they were treated as separate measures for analysis. Accordingly, the endpoint’s intended role can be described, but its observed result and precision cannot be evaluated from the registry record. The no-treatment group has no primary outcome data reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial’s design and outcome description provide the framework needed to understand what a valid comparison would address. The first 12 weeks form the randomized, blinded vehicle-controlled period. A comparison during this period can be interpreted as a contrast between assignment to delgocitinib cream and assignment to vehicle, subject to the trial’s analysis methods and the completeness of outcome data. After that period, both described arms received open-label delgocitinib. The later phase therefore has no concurrent vehicle group in the arm descriptions and cannot preserve the original randomized treatment contrast in the same way.

What a treatment contrast represents

As general statistical context, a randomized comparison estimates how outcomes differ between groups assigned to different study treatments, rather than simply describing change within one group. Within-group change can reflect treatment, natural fluctuation, measurement variation, or other influences over time. A between-group comparison helps distinguish the treatment contrast from changes that may also occur under the comparator. The registry record does not post a primary treatment contrast for the molecular endpoint, so that contrast cannot be assessed.

The primary outcome is expressed as fold-changes in the expression of three named markers. As general context, a fold-change describes a relative change in a measured quantity, but its interpretation depends on how the measurement and analysis are defined. The record does not provide the underlying marker values, the transformation used, or a rule for combining the three markers. It would therefore be inappropriate to assume a particular scale, summary statistic, or composite endpoint.

Estimates and uncertainty

As general statistical context, an effect estimate describes the size and direction of a group difference, while a confidence interval describes the range of values reasonably compatible with the observed data under the method used. A narrow interval typically indicates greater precision than a wide one, though interpretation also depends on the endpoint and design. Neither an estimate nor an interval for the primary outcome is reported in the registry record. A significance test alone, if one were reported, would not communicate the size or precision of an effect; no primary endpoint test is posted.

The analysis would also need to address the fact that three molecular markers are named. As general context, when several endpoints or comparisons are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiplicity. Possible approaches depend on the scientific aims and prespecification. The registry record does not report whether these markers were analyzed separately, whether any multiplicity procedure was planned, or whether one marker had priority over the others. It is therefore not possible to evaluate how multiple results would have been interpreted.

Distribution and model choices

As general context, statistical methods should reflect the outcome’s scale and distribution. Fold-change measures may have distributions that differ from the assumptions of a simple normal model, but the record does not report the observed distributions or the chosen analysis method. It would be speculative to say whether a transformation, a nonparametric method, or a particular model was used. The registry record also does not report adjustment variables, handling of repeated measurements, or an approach for values that could not be measured.

The design includes measurements at baseline and Week 12 for the primary endpoint. General approaches to repeated measurements can compare follow-up values while accounting for baseline values, or model changes over time, but the appropriate method depends on the protocol and data. No such method is described in the registry record. The timepoint labels alone do not identify the analysis model or establish whether all randomized participants contributed measurements at both times.

Planning assumptions and observed data

The record describes planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such illustrations are calculations for planning under stated assumptions, not observed trial results and not observed power. The registry record does not report the original sample-size justification. It also does not provide the primary effect estimate needed to assess the assumptions behind a planning illustration, or a reported planning result in the registry record for this analysis.

As general context, a planned sample size is selected before outcomes are known to target a desired precision or probability of detecting an effect under assumptions. Observed power, calculated after seeing the results, is not a substitute for an effect estimate and its uncertainty. The record does not report enough information to assess the trial’s power or the adequacy of its enrollment for the molecular endpoint.

The registry lists zero posted analyses. This means the registry record does not include an analysis result for the primary outcome in the information. It does not establish that no analyses were conducted outside the registry; it means their methods and results are not reported in the registry record. Readers should distinguish that reporting limitation from evidence that an effect was absent.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint names three molecular measures: CXCL9, CXCL10, and IFN-γ. The registry record does not state whether each marker was a separate primary outcome, whether the markers were combined, or whether one was designated as the main marker. It also does not report a multiplicity strategy. As general statistical context, multiplicity matters when several outcomes or contrasts are evaluated because it affects how evidence from individual tests should be interpreted. Without the prespecified approach and the results, the impact cannot be assessed.

Missing-data methods are not reported in the registry record. The record does not describe how participants without a Week 12 measurement, measurements outside an expected range, or incomplete safety information were handled. It also does not state whether the primary analysis included all randomized participants, participants who received treatment, or another analysis population. The enrollment figure alone does not answer those questions, and the safety groups’ listed at-risk counts should not be treated as an analysis-population definition for the primary endpoint.

The registry record does not report an interim analysis plan or whether interim analyses were conducted. It does not provide a statistical analysis plan, a detailed model specification, or a rationale for the enrollment target. These items are not established by the trial’s randomized or double-blind labels. Their absence limits assessment of prespecification, missing-data handling, and the way multiple outcomes were intended to be interpreted.

Because primary outcome estimates and analyses are not posted, there is no basis in the registry record for evaluating the robustness of a molecular result to alternative missing-data assumptions or multiplicity adjustments. These are reporting gaps, not evidence that missing data or multiplicity did or did not affect the study’s findings.

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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for the two treatment sequences. In the delgocitinib-then-delgocitinib group, 0 of 15 participants at risk were recorded as affected by serious adverse events. In the vehicle-then-delgocitinib group, the corresponding count was also 0 of 15. The no-treatment group is listed with 0 participants at risk, so it does not provide a treatment safety comparison.

The record also lists 6 participants with other adverse events in the delgocitinib group and 10 in the vehicle group. These counts are distinct from the serious adverse-event counts. The listed number of participants affected does not tell readers how many total events occurred, how severe non-serious events were, when each event began, or whether investigators considered events related to treatment. No serious adverse-event terms are listed in the posted record.

These figures are descriptive. They do not establish that either treatment caused or prevented an event, and the registry record does not report a statistical comparison of the safety counts. Interpretation should also account for the sequences: after the blinded first 12 weeks, both treatment groups received open-label delgocitinib for another 12 weeks. The registry information presented for the safety counts does not specify enough detail to attribute events to a particular treatment period.

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

The registry record establishes that an exploratory Phase 2a randomized, double-blind, vehicle-controlled trial was conducted in adults with FFA. It describes a molecular primary endpoint, the initial blinded treatment comparison, a later open-label delgocitinib period, and selected safety counts. This supports a clear description of the study question and design.

It does not establish the size or direction of the primary molecular effect. The record does not report the fold-change results, group estimates, uncertainty intervals, or primary analysis. It also does not report the clinical efficacy results described in the study summary. Consequently, the available information cannot show whether delgocitinib changed the molecular signature relative to vehicle, nor whether any molecular change corresponded to a clinical outcome.

The safety counts show that no serious adverse events were recorded among the listed at-risk participants in either treatment group, while other adverse events were recorded for participants in both groups. These counts are not a complete characterization of safety, and they do not establish a causal difference. The registry record does not provide enough event detail or timing to determine whether an event occurred during the blinded or open-label period.

As general context, absence of a posted result is not the same as a result showing no effect. Similarly, the fact that a trial was randomized and blinded does not replace the outcome estimates needed to judge the observed comparison. The record gives no basis for a claim that delgocitinib works or does not work. It also gives no basis for determining how precisely the intended effect was estimated. The evidence that can be described is limited to the design, stated endpoint, and posted safety counts.

13. Why This Trial Matters Statistically

This trial illustrates how a registry record can describe an ambitious biological question while offering little information for judging the observed treatment effect. The primary endpoint targets expression of CXCL9, CXCL10, and IFN-γ, linking the study’s interest in the molecular signature of FFA to a comparison of delgocitinib cream with vehicle. The endpoint and timeframe are specified, but the result is not. Statistical interpretation depends on estimates, uncertainty, and analysis details, not only on a stated research aim.

The treatment sequence also matters. The first 12 weeks are described as randomized and blinded, which defines the principal vehicle-controlled contrast. Both groups then receive open-label delgocitinib for another 12 weeks. A reader must separate that initial comparison from later observations, when the arm descriptions no longer include an ongoing vehicle group. This is a design distinction, not a conclusion about treatment effects.

The healthy-skin molecular reference serves another purpose from the vehicle arm. The registry states that no primary outcome data were collected for the no-treatment group, so it cannot be treated as a third source of comparative efficacy data. Clear separation of biological reference groups and randomized treatment comparators is essential to avoid overstating what a study can answer.

Finally, the record shows why reporting analysis plans and results is central to scientific interpretation. Three markers are named, yet their analysis hierarchy and multiplicity handling are not reported. No primary effect estimates or analysis are posted. The posted safety counts add limited descriptive information but cannot fill those gaps. A well-defined design question and a completed trial status do not alone communicate the magnitude, precision, or clinical relevance of an outcome.

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 most consequential limitation for interpreting this trial from the registry record is the absence of primary outcome results. No group-level fold-changes, treatment contrast, uncertainty intervals, or primary statistical analysis are reported. The record therefore cannot support an estimate of the molecular effect or its precision.

The registry also does not report clinical efficacy results, despite describing clinical effect as an objective. It does not give detailed outcome definitions for a clinical endpoint in the registry record. The molecular endpoint includes three markers, but the record does not explain whether they were analyzed separately or jointly, or how multiple comparisons were handled.

Details needed to assess the analysis are not reported in the registry record. These include the statistical model, analysis populations, missing-data methods, handling of measurements that could not be obtained, and the statistical analysis plan. The record does not give a sample-size justification. These omissions prevent assessment of whether the intended comparison and analysis were prespecified and how the available data were used.

The safety information is limited to counts of participants affected by serious and other adverse events, without event-level descriptions or enough timing information to distinguish the blinded period from the open-label period. The no-treatment group has no participants listed at risk for the posted safety figures and no primary outcome data. It cannot serve as a concurrent treatment safety comparator based on these counts.

The trial is described as single-site and exploratory, but the registry entries do not characterize how broadly its results might apply. Since primary and clinical results are not reported, generalizability of an observed effect cannot be evaluated. These are limitations of what the registry record reports, not proof that unreported analyses or results do not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Trial to Assess the Effect of Delgocitinib Cream 20 mg/g on the Molecular Signature, Safety, and Efficacy in Adults With Frontal Fibrosing Alopecia — NCT05332366.
• Registry record last updated 2025-03-06; status last verified 2025-02.
• Results first posted 2025-02-07.
• 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

NCT05332366 is a completed Phase 2a randomized, double-blind, vehicle-controlled, single-site exploratory trial of delgocitinib cream 20 mg/g in adults with frontal fibrosing alopecia. Enrollment was 35. The recorded study start was 2022-04-19, and primary completion was 2023-02-13.

Participants were assigned to delgocitinib cream or vehicle for the first 12 weeks, followed by open-label delgocitinib for another 12 weeks in both described treatment groups. A no-treatment group provided a healthy-skin molecular signature; the registry reports no primary outcome data for that group.

The primary outcome concerned baseline-to-Week 12 changes in CXCL9, CXCL10, and IFN-γ expression. Primary outcome estimates and analyses are not reported in the registry record. Safety listings show 0 serious adverse events among 15 at-risk participants in each treatment group, and other adverse events affecting 6 and 10 participants, respectively. These counts do not establish a causal treatment difference.