A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis (NCT03738800), a randomized phase 2 study. The primary outcome is The Percentage of Subjects in Each Treatment Group Who Experienced Successful Resolution of LI..

2. Clinical Question

The primary endpoint therefore combines an absolute status at follow-up with change from baseline. A participant had to meet both conditions; a favorable score on only one part would not satisfy the registry definition. The registry also lists a 90-day open-label extension after the double-blind period, but the primary endpoint is specified for the double-blind period at Day 90 or end of treatment.

The practical statistical question is whether the posted counts support a distinguishable difference in success between either cream strength and vehicle. The counts show two successes in the 100 µg/g group and none in the other groups. The risk-difference estimate for that comparison is positive, but its confidence interval includes no difference. These observations describe the posted endpoint results; they do not by themselves establish a treatment effect or settle the broader clinical question.

3. Trial Design

The registry describes NCT03738800 as a phase 2, randomized, multicenter, double-blind, vehicle-controlled, parallel-group study of CD5789 cream. Masking is recorded as quadruple. The study was designed to assess safety, efficacy, and systemic exposure in adults and adolescents with autosomal recessive ichthyosis with lamellar scale. Its double-blind period was 90 days, followed by a planned 90-day open-label extension.

The randomized groups received topical CD5789 cream at 200 µg/g, CD5789 cream at 100 µg/g, or vehicle. Each arm description specifies a 50g topical treatment. The registry lists enrollment of 65. For the primary endpoint, the posted group sizes are 15 for the 200 µg/g arm, 17 for the 100 µg/g arm, and 17 for vehicle. Those endpoint group sizes should be read as the groups contributing to the reported outcome, not as a replacement for the registry’s enrollment figure.

The study start is recorded as 2019-05-01, primary completion as 2021-09-03, and status as terminated. The registry record does not report why the study was terminated or whether the open-label extension was completed. It also does not report the allocation ratio, the specific randomization method, or the masking procedures used to maintain blinding.

The registry lists 17 outcome measures and no reported analyses. It provides summary outcome data and unadjusted recalculations for selected comparisons, but a complete statistical analysis plan and details of the analysis population are not reported in the registry record. In particular, it is not reported in the registry record whether the primary comparison was prespecified as the main inferential test or how participants with missing Day 90 assessments were handled. Those omissions limit assessment of how closely the posted summaries reflect the original 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.

Double-blind Treatment Period

Reasons for not completing this period:

Open Label Extension

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 The Percentage of Subjects in Each Treatment Group Who Experienced Successful Resolution of LI., measured over 90 Days.

The primary endpoint is the count of participants in each treatment group who achieved successful resolution of lamellar ichthyosis at Day 90 or end of treatment during the double-blind period. The registry defines success using the 5-point full-body Investigator Global Assessment scale: treated areas had to be clear or almost clear, and the participant also had to have at least a 2-grade change from baseline. Both conditions are part of the definition.

This type of endpoint combines a clinician-rated overall status with a minimum amount of improvement. It is intended to distinguish participants who reach a specified state and improve sufficiently from baseline, rather than simply describing a group’s average score. For a binary endpoint, each participant either meets the stated success definition or does not; the group result is then summarized as a count or proportion.

The registry gives the endpoint unit as participants and reports counts: zero successes in the 200 µg/g group, two in the 100 µg/g group, and zero in vehicle. The record does not provide a separate percentage for each group. The primary endpoint’s exact operational details, including who rated the scale and how assessments were standardized across centers, are not reported in the registry record.

A threshold-based endpoint is straightforward to interpret, but it can discard information about the degree of change among participants who do not cross the success threshold. It also depends on consistent application of the rating scale and the specified threshold. The endpoint therefore answers a focused question about achieving the defined response at the stated time, not every question about severity, symptoms, quality of life, or longer-term outcomes.

7. Results Posted in the Registry

• CD5789 Cream 200 µg/g: 0.0% (0/15) versus 0.0% (0/17) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• CD5789 Cream 100 µg/g: 11.8% (2/17) versus 0.0% (0/17) on control; risk difference 11.8 percentage points (95% CI -3.6 to 27.1); unadjusted two-proportion z-test p = 0.145.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Total 16-point Visual Index for Ichthyosis Severity (VIIS)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • CD5789 Cream 200 µg/g: mean 10.90 versus 11.40 on control; difference -0.50 (95% CI -3.06 to 2.06), standardized effect d = -0.14; z-test p = 0.702.
  • CD5789 Cream 100 µg/g: mean 10.90 versus 11.40 on control; difference -0.50 (95% CI -2.68 to 1.68), standardized effect d = -0.15; z-test p = 0.653.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CD5789 Cream 200 µg/g and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CD5789 Cream 100 µg/g and the control. The interval gives the range of effects that remain compatible with the data.

The Difference in Mean Scores Using Individual Score for Roughness

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • CD5789 Cream 200 µg/g: mean 2.70 versus 3.10 on control; difference -0.40 (95% CI -1.07 to 0.27), standardized effect d = -0.42; z-test p = 0.241.
  • CD5789 Cream 100 µg/g: mean 2.70 versus 3.10 on control; difference -0.40 (95% CI -1.00 to 0.20), standardized effect d = -0.45; z-test p = 0.191.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CD5789 Cream 200 µg/g and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CD5789 Cream 100 µg/g and the control. The interval gives the range of effects that remain compatible with the data.

The Difference in Mean Scores Using Palm Sole Assessment

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • CD5789 Cream 200 µg/g: mean 2.10 versus 2.60 on control; difference -0.50 (95% CI -1.24 to 0.24), standardized effect d = -0.47; z-test p = 0.183.
  • CD5789 Cream 100 µg/g: mean 1.60 versus 2.60 on control; difference -1.00 (95% CI -1.79 to -0.21), standardized effect d = -0.85; z-test p = 0.013.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CD5789 Cream 200 µg/g and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for CD5789 Cream 100 µg/g than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes cover several aspects of ichthyosis severity, skin roughness, palm and sole assessment, fissures, and quality of life. Numeric summaries are posted for selected score-based outcomes at 90 days. Across these measures, the pattern is not uniformly consistent: some comparisons favor an active group in their observed direction, while others show little separation in group averages. This mixed pattern does not provide a single coherent confirmation of the primary endpoint.

The primary endpoint counts successful resolution using a threshold on the full-body IGA scale, whereas secondary measures capture other dimensions or use continuous scores. Different measures can therefore tell different parts of the clinical story, and a score-based difference does not automatically imply that more participants met the primary success definition. Conversely, a sparse primary endpoint may fail to reflect changes that are visible in continuous measures. The registry record does not report a formal analysis linking secondary changes to primary endpoint response.

At least one secondary comparison has an unadjusted p-value of 0.013. It is one result among multiple outcomes and comparisons. When many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis accounts for multiplicity. The registry record does not report a multiplicity adjustment, testing hierarchy, or designation of confirmatory secondary outcomes. The unadjusted secondary findings should consequently be treated as exploratory rather than as independent confirmation.

Some secondary outcomes listed in the registry do not have numerical results in the posted outcome summaries. The record does not explain why those results are absent. Without complete outcome reporting and a prespecified interpretation framework, it is difficult to assess whether the pattern is selective or how much weight each result was intended to carry. The secondary results offer context, but they do not resolve the uncertainty in the primary comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Total 16-point Visual Index for Ichthyosis Severity (VIIS)
• The Difference in Mean Scores Using Individual Score for Roughness
• The Difference in Mean Scores Using Palm Sole Assessment
• The Difference in Proportion of Subjects With Presence of Fissures on Palms Between the Active and Vehicle Groups
• Quality of Life Measurement Per Dermatology Life Quality Index (DLQI)
• The Difference in Proportion of Subjects With Presence of Fissures on Soles Between the Active and Vehicle Groups

9. Statistical Interpretation

10. Statistical Methods Explained

Statistical methods help distinguish the observed group summaries from the uncertainty and assumptions involved in comparing groups. The registry record supplies counts for the binary primary endpoint and means with standard deviations for selected continuous secondary outcomes. The recalculated comparisons are described as unadjusted. Sponsor-reported analyses are not listed, so the recalculations should not be mistaken for a full account of the original analysis.

What a risk difference describes

For a binary outcome, a risk difference expresses the difference between the proportions meeting the endpoint in two groups. A value of zero corresponds to equal observed proportions; positive or negative values indicate which group had the larger observed proportion, according to the subtraction order used. For the 100 µg/g comparison, the estimate is 0.118, with vehicle as the comparator. The calculation is based on two successful outcomes in the active group and none in vehicle. The result is an estimate from these groups, not a guarantee of the difference in a wider population.

When events are rare, small changes in the event count can have a substantial effect on the estimate. If neither group has an event, the observed risk difference is zero, but that observation does not demonstrate that the underlying risks are identical. Methods for interval estimation in sparse data can behave differently, especially when there are no observed events in either group. The registry record does not report the interval method used for the primary endpoint, so the zero-width interval for the 200 µg/g comparison cannot be independently evaluated from the record.

How confidence intervals and p-values differ

A confidence interval gives a range of values compatible with the data under the calculation’s assumptions and conveys the uncertainty around an estimate. It is not a guarantee that the true value falls in the interval, nor does it measure clinical importance. When an interval for a difference includes zero, the data are compatible with no difference under that method, while also allowing differences in either direction if the interval spans both. For the 100 µg/g comparison, the interval crosses zero.

A p-value summarizes how unusual data at least as incompatible with a specified null model would be, assuming that model and the test assumptions. It does not give the probability that a treatment works, that the null is true, or that a result will replicate. The primary p-value is unadjusted. The registry record does not report a prespecified testing hierarchy or a correction for the multiple outcomes and comparisons.

Interpreting continuous outcomes

For the posted continuous secondary outcomes, the groups are described using means and standard deviations. The mean is a measure of the group’s average score; the standard deviation describes the spread of individual scores around that mean. A mean difference compares two group averages. Its confidence interval conveys uncertainty in the difference, subject to the assumptions of the calculation. A confidence interval that includes zero does not establish equality; it indicates that the summary does not clearly separate the groups from no difference under that method.

Standard deviations are not standard errors. A standard deviation describes variation among participant measurements, while a standard error describes uncertainty in an estimated statistic. The recalculated comparisons list standard errors for the group means and pooled standard deviations for standardized comparisons. The registry record does not provide participant-level distributions, so the shape of score distributions, presence of outliers, and appropriateness of a normal approximation cannot be examined from the summaries alone.

Why over-dispersion can matter

As a general statistical point, over-dispersion occurs when the variation in observed data exceeds what a model assumes. For count or binary outcomes, excessive variation or clustering can make standard errors too small if the analysis assumes observations are more independent or homogeneous than they are. Multicenter studies can also have patterns that differ across centers. Whether over-dispersion or center-level effects were relevant in this study is not reported in the registry record, and the posted summary statistics cannot resolve that question.

Planning illustrations are not observed power

The posted planning illustrations are based on observed effects and are explicitly not the trial’s own design calculation. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. Such calculations show how estimated sample-size needs can change with the assumed effect and target power. They are not observed power, do not show the probability that this completed study detected a true effect, and should not be read as a justification for the trial’s enrollment. The original sample-size assumptions and justification are not reported in the registry record.

Overall, the methods support cautious reading: the primary estimate is based on few events, continuous-outcome comparisons are summary-level and unadjusted, and the record lacks detail about the original model and analysis procedures. These limitations do not invalidate the posted calculations, but they restrict the conclusions that can be drawn from them.

11. Confidence Intervals and Precision

The primary endpoint estimates have limited precision. In the 100 µg/g versus vehicle comparison, the risk difference is 0.118 and the confidence interval runs from -0.035 to 0.271. Because the interval includes zero and extends in both directions, the observed positive estimate is uncertain: the posted summary is compatible with no difference and with effects in either direction under the interval method.

The small number of observed successes is important to that interpretation. There are two successes in the 100 µg/g group and none in vehicle. With sparse binary outcomes, a small change in the observed count can strongly affect the estimated difference and its interval. The estimate should therefore not be treated as a stable measure of the size of an effect.

For 200 µg/g compared with vehicle, the reported risk difference is 0.0 and the confidence interval is 0.0 to 0.0. Both groups have zero observed successes. Although those counts give an observed difference of zero, the identical interval limits do not adequately communicate ordinary sampling uncertainty for a rare event comparison. The interval method is not reported in the registry record, so this result warrants particular caution rather than a conclusion of exact equivalence.

Confidence intervals address statistical uncertainty under a method; they do not address all sources of uncertainty. The record does not report how missing assessments were handled, which participants entered each analysis population, or whether adjustments were made in the sponsor’s own analysis. It also does not report a clinical threshold for a meaningful difference. Consequently, the precision of the posted comparison should be separated from questions of clinical importance, generalizability, and robustness to analysis choices.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures and includes multiple secondary outcomes. Comparing two active strengths with vehicle across more than one endpoint creates multiple opportunities to observe a nominally unusual result, even when no underlying differences exist. Statistical approaches such as a prespecified testing hierarchy or adjustment for multiple comparisons can control how results are interpreted. The registry record does not report whether such an approach was planned or used. The primary comparison is therefore read alongside unadjusted secondary results without a documented multiplicity framework.

Missing-data handling is also not reported in the registry record. The endpoint group sizes are 15 for 200 µg/g, 17 for 100 µg/g, and 17 for vehicle, while the registry lists enrollment of 65. These figures describe different record entries and should not be treated as a complete account of participant flow. The record does not state how many participants completed the double-blind period, whether any Day 90 assessments were missing, or how missing outcome values were handled.

The analysis populations are not reported in the registry record. It is unclear whether the posted summaries use all randomized participants, only participants with an available endpoint assessment, or another population. The record also does not describe adherence, protocol deviations, exclusions, or imputation. These details matter because the handling of incomplete outcomes can affect both group estimates and the interpretation of a randomized comparison.

The registry reports no sponsor analyses for the posted outcomes. Thus, the recalculated unadjusted comparisons should not be assumed to reproduce a prespecified primary analysis. The record does not report the statistical analysis plan, including covariate adjustment, handling of center effects, or rules for endpoint adjudication. These omissions do not prove that such procedures were absent from the full study, but they are not documented in the registry record and limit independent assessment.

13. 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 posted serious adverse event summaries report zero serious adverse events in each group. The corresponding numbers at risk are 23 for the 200 µg/g group, 21 for the 100 µg/g group, and 21 for vehicle. No deaths are reported in these groups. The registry also reports other adverse events affecting 10 participants in the 200 µg/g group, 7 in the 100 µg/g group, and 11 in vehicle; these are not the serious-event counts.

Safety summaries need to be read using their own denominators. The numbers at risk for adverse events differ from the group sizes posted for the primary efficacy endpoint, so those sets of figures should not be conflated. The registry record does not explain the difference in populations or exposure periods, and it does not provide event-level descriptions for the other adverse events in the posted summary.

Zero reported serious events in these groups means none were recorded in the displayed safety summaries. It does not establish that the risk of serious events is absent, particularly in a study of this size and duration. The registry record does not report detailed event narratives, exposure-adjusted rates, or a full safety analysis. These figures are descriptive and should not be used alone to draw broader safety conclusions.

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

The primary endpoint results describe a small number of participants meeting a specified response definition during the double-blind period. There are no recorded successes in the 200 µg/g group or vehicle, and two in the 100 µg/g group. The estimated risk difference for 100 µg/g versus vehicle is positive, but its confidence interval includes zero and is wide enough to allow differences in either direction. The posted primary results therefore do not establish a clear difference between either active cream strength and vehicle.

This interpretation is not the same as concluding that the creams have no effect. A result that does not clearly distinguish groups can arise from a truly small or absent difference, but it can also reflect imprecision, sparse events, or other features of the data and analysis. The registry summaries alone cannot resolve among these explanations. Likewise, the two observed successes in one group do not by themselves prove that the group’s underlying response probability differs from vehicle.

The endpoint is specific: it requires clear or almost clear treated areas plus at least a 2-grade change on the full-body IGA scale by Day 90 or end of treatment. The findings do not answer every question about symptom burden, changes in individual disease features, longer-term outcomes, or quality of life. Secondary outcomes provide related information, but their unadjusted results do not replace the primary endpoint or establish a confirmatory conclusion.

The study status is terminated, and the registry record does not report why. The record also does not report the sponsor’s inferential analysis, analysis populations, or missing-data procedures. These gaps constrain interpretation. The appropriate statistical conclusion is limited to the posted summaries: observed counts and estimates are available, but the primary comparison is imprecise, and the record does not support a definitive conclusion about a treatment effect.

These observations are not medical advice and do not determine what treatment is appropriate for an individual. They are a description of this study’s registry results, with the uncertainty and reporting limitations stated above.

15. Why This Trial Matters Statistically

This trial illustrates why an observed difference and a reliable conclusion are not the same thing. The primary endpoint is clinically interpretable as a defined response, but the posted counts are sparse. A positive point estimate for one active group may attract attention; the confidence interval shows why it cannot be read alone. The interval includes zero, and the result remains uncertain.

The zero-event comparison is also instructive. Identical observed counts produce an observed risk difference of zero, but the reported zero-width interval should not be mistaken for certainty that the underlying groups are identical. Sparse binary data require careful interval methods and transparent reporting. When the method is not documented, readers have limited ability to evaluate whether the uncertainty has been represented appropriately.

Multiple endpoints create another interpretive challenge. The registry includes a range of severity, skin-feature, fissure, and quality-of-life measures. Those outcomes can add context, but unadjusted secondary comparisons have less evidential weight when the testing strategy is not reported. A nominally notable result among several comparisons should be treated cautiously and not promoted to a definitive finding without a prespecified framework.

Finally, registry summaries are only as interpretable as their accompanying information. Enrollment, endpoint group sizes, and safety denominators serve different purposes; the analysis population and handling of missing data are not reported. The trial is a useful case study in reading estimates, intervals, sparse outcomes, and secondary findings together, while keeping conclusions proportional to what the record documents.

16. 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 is the scarcity of primary endpoint events: the posted counts are zero, two, and zero across the three groups. This makes the estimated difference sensitive to individual outcomes and limits precision. The confidence interval for the 100 µg/g comparison spans zero, while the reported interval for the 200 µg/g comparison has identical limits despite zero events in both groups. The interval method is not reported, limiting evaluation of the latter calculation.

The registry record does not provide a complete account of participant flow or the analysis population. It lists enrollment of 65, while the primary endpoint summaries report group sizes of 15, 17, and 17. The reason for those differences and the treatment of any missing assessments are not reported in the registry record. Without this information, it is difficult to assess potential bias from exclusions or incomplete follow-up.

The study status is terminated, but the reason is not reported in the registry record. The record does not establish whether the planned open-label extension was completed. The sponsor’s analysis, statistical analysis plan, sample-size justification, and any interim analyses are also not reported. The planning illustrations based on observed effects cannot fill those gaps or establish the study’s original design rationale.

The record lists multiple outcome measures, but it does not report a multiplicity strategy or a testing hierarchy. Secondary comparisons are therefore difficult to interpret as confirmatory evidence. Some listed outcomes lack numerical summaries in the posted outcome results, and the reason is not reported. The record also lacks detailed safety event descriptions and information about assessment consistency across centers. These limitations constrain generalizability and independent evaluation of the results.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Safety, Efficacy and Systemic Exposure Study of CD5789 Cream in Adults and Adolescents With Lamellar Ichthyosis — NCT03738800.
• Registry record last updated 2023-08-14; status last verified 2023-02.
• Results first posted 2023-08-14.
• 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.

20. Record Summary

NCT03738800 is a phase 2 randomized, multicenter, quadruple-masked, parallel, vehicle-controlled study of topical CD5789 cream in adults and adolescents with lamellar ichthyosis. It compared 200 µg/g cream and 100 µg/g cream with vehicle during a 90-day double-blind period, followed by a planned 90-day open-label extension. The registry lists enrollment of 65 and records the study as terminated.

The primary endpoint was successful resolution at Day 90 or end of treatment, requiring clear or almost clear treated areas and at least a 2-grade improvement from baseline on the 5-point full-body IGA scale. Posted counts were zero of 15 for 200 µg/g, two of 17 for 100 µg/g, and zero of 17 for vehicle. The 100 µg/g risk-difference estimate was 0.118, with a confidence interval from -0.035 to 0.271 and an unadjusted p-value of 0.145.

The registry record does not report the sponsor’s inferential analyses, analysis populations, missing-data methods, or reason for termination. The primary comparison is imprecise, and the posted summaries do not establish a clear difference from vehicle.