Topically Applied AMTX-100 CF for Adult Patients With Mild to Moderate Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topically Applied AMTX-100 CF for Adult Patients With Mild to Moderate Atopic Dermatitis (NCT04313400), a randomized phase 1, phase 2 study. The primary outcome is Part 2 (Phase II) Primary: Proportion of Responder Subjects at Day 28.

2. Clinical Question

The registry describes the study as randomized and vehicle-controlled, with a parallel-group model and quadruple masking. Its official title describes a double-blind study. The primary comparison is limited to the Part 2 responder endpoint; the Part 1 dose-escalation cohorts addressed maximum tolerable dose by the maximum BSA percentage treated, as well as safety and efficacy. The posted record gives the primary endpoint percentages and group sizes, but notes that subjects were missing in both groups. The reasons for missingness and the methods used to address it are not reported in the registry record.

3. Trial Design

This completed study is registered as NCT04313400 and has Phase I and Phase II components. The registry records enrollment of 91 and lists atopic dermatitis as the condition. The study began on 2020-03-10, and primary completion was recorded as 2023-12-19. Its official title describes a multi-center, double-blind, randomized, vehicle-controlled study; the masking entry is quadruple and the model is parallel.

The design had two parts with different purposes and approaches. Part 1 was an open-label dose-escalation component. Five cohorts were sequentially enrolled and received AMTX-100 CF 1.1% w/w, applied twice daily for 7 consecutive days to treatable affected areas. The recorded range of BSA treated was 3% to 70%. This part was intended to determine maximum tolerable dose by maximum BSA percentage treated. It was not the randomized vehicle-controlled comparison represented by the primary endpoint.

Part 2 was the Phase II comparison. Group A received AMTX-100 CF3 at 1.1% w/w and Group B received placebo vehicle at 0% w/w. Both were applied twice daily for 28 consecutive days to treatable affected areas. The primary outcome was assessed at Day 28, and the registry also lists secondary outcomes at other time points, including Day 42 for several measures. The record does not describe the randomization procedure, allocation concealment, or details of how masking was maintained.

The enrollment descriptions in the study summary refer to approximate planned enrollment for each part, whereas the registry separately records overall enrollment. No sample-size justification or statistical design assumptions for the trial itself are reported in the registry record. The planning illustrations associated with the posted DLQI comparison are recalculations from observed summaries, not evidence of the trial's original design or observed power.

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.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Part 2 (Phase II) Primary: Proportion of Responder Subjects at Day 28, measured over Day 28.

The primary endpoint is the proportion of Part 2 subjects who were responders at Day 28. A responder had to meet both elements of the definition: a vIGA-AD score of 0, meaning clear, or 1, meaning almost clear, on a 5-point scale; and a reduction of at least 2 points from baseline. A subject who received rescue treatment was counted as a non-responder.

Combining a threshold for the final clinical assessment with a required improvement from baseline makes the endpoint more specific than either condition alone. It requires both a low score at the assessment and change relative to the subject's starting score. Treating rescue-treated subjects as non-responders also makes rescue treatment part of the responder rule rather than a separate favorable outcome.

The registry reports the outcome as a percentage, while its description refers to a proportion, and notes that percentage was used to present the result more clearly. The posted percentages are 3.8% for AMTX-100 CF and 9.7% for placebo. The corresponding group sizes are 26 and 31. The registry notes that subjects were missing in both groups, but does not report further details about missingness or the analysis population. The record does not provide an interval estimate or inferential comparison for this primary outcome, so the percentages alone do not establish the precision of the group contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish the posted estimates from the strength of evidence they can support. The registry records a primary endpoint as a responder percentage, while the secondary DLQI result is a comparison of group means. These outcome types are interpreted differently, and the information available for the two outcomes is not equally complete.

What does a responder percentage convey?

A responder percentage describes the share of the relevant group meeting a prespecified outcome definition. Here, response required both a qualifying vIGA-AD score and a reduction from baseline, with rescue-treated subjects classified as non-responders. A percentage is easy to interpret as a frequency, but it does not by itself express uncertainty around the estimate or around the difference between groups. Such uncertainty is commonly described with a confidence interval or a statistical test. Neither is reported for this primary outcome in the registry record.

Missing outcome data complicate the interpretation of a percentage. The registry notes missing subjects in both primary-outcome groups but does not explain their handling. If an analysis excludes subjects without an assessment, the resulting percentage describes the observed subjects; if missing subjects are assigned an outcome or handled using another method, the estimate may have a different interpretation. The record does not say which approach was used. The responder rule's treatment of rescue therapy is specified, but that does not resolve how other missing observations were treated.

How should the DLQI comparison be read?

The DLQI result is a mean percent change from baseline. The posted means are -26.6 for AMTX-100 CF and -36.3 for placebo. The recalculated mean difference is 9.7, defined as the AMTX-100 CF mean minus the placebo mean. The negative means indicate reductions from baseline; the positive difference reflects a less negative mean change in the AMTX-100 CF group. The interval from -22.1 to 41.5 expresses uncertainty around this estimated difference. In general, a confidence interval gives a range of values reasonably compatible with the data under the method's assumptions. An interval that includes zero does not demonstrate a clear group difference, but it also does not prove that the groups are equivalent.

The unadjusted p value is 0.55. In general, a p value measures how incompatible the observed data are with a specified null hypothesis, under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. This p value is an unadjusted recalculation from posted summaries. It is not a reported sponsor analysis, and no sponsor analysis for the DLQI comparison is listed. The discrepancy flag is false, so there is no reported conflict between the recalculation and a sponsor analysis.

Standard deviations describe variation among observations around a mean. The posted DLQI standard deviations are 42.14 for AMTX-100 CF and 75.35 for placebo. In general, unequal variability can affect the suitability of methods that assume equal variances. Over-dispersion is a related concern for count or proportion data: if observations vary more than a model expects, standard errors may be too small and intervals too narrow. The primary endpoint is a responder proportion, but the record does not report a statistical model or variance method for it. The registry also does not report a statistical plan, so the precise assumptions behind a sponsor analysis cannot be assessed.

What do the planning illustrations mean?

The planning illustrations are based on the observed DLQI effect and specify a two-sided significance level of 0.05, equal allocation, and a normal approximation. They show participants per arm for 80% power and for 90% power when planning for 100%, 75%, or 50% of the observed effect. For planning for 100% of the observed effect, the values are 660 and 883 participants per arm, respectively. For planning for 75% of the observed effect, they are 1,173 and 1,570. For planning for 50% of the observed effect, they are 2,638 and 3,531.

These values are illustrations for future planning under the stated assumptions, not a reconstruction of the trial's design and not observed power. Using an observed effect as the planning basis can be unstable, particularly when the estimate is imprecise. Planning for a smaller fraction of that effect yields larger illustrative sample sizes because smaller differences are harder to distinguish statistically under otherwise fixed assumptions. The trial's own sample-size justification is not reported in the registry record.

The record does not report whether interim analyses were planned or conducted, the primary analysis model, a multiplicity strategy, or the definitions of the analysis populations. Without those details, the estimates should be interpreted as posted summaries rather than as a complete account of the prespecified statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy for the primary and secondary outcomes. The listed secondary measures cover several clinical domains and include assessments at multiple time points. When many outcomes are tested, the chance of finding at least one apparently unusual result by chance can increase. In general, prespecifying a hierarchy or using an adjustment can help control that risk. Whether either approach was used in this study is not reported in the registry record. The DLQI p value is an unadjusted recalculation and should be interpreted with that limitation.

For the primary endpoint, the record states that subjects were missing in both groups. It does not report the number of missing observations, reasons for missingness, whether missingness differed by group, or the method used to handle missing data. The protocol's responder definition specifies that rescue-treated subjects count as non-responders, but it does not explain how other missing Day 28 assessments were analyzed. These omissions limit assessment of how well the reported percentages represent the randomized groups.

The analysis populations are not reported in the registry record. The primary group sizes are 26 and 31, while the safety record lists separate at-risk group sizes for its safety summaries. The record does not explain the relationship between those denominators and the analysis population used for the primary endpoint. They should not be assumed to be interchangeable.

The registry does not report a statistical analysis plan, the primary comparison method, a sample-size justification, or whether interim analyses were planned or conducted. Nor does it provide the full analysis details needed to evaluate model assumptions or prespecified handling of protocol deviations. These details matter because they determine how endpoint observations contribute to estimates and how uncertainty is quantified. In their absence, interpretation should stay close to the posted summaries and distinguish them from any unreported sponsor analyses.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The safety record lists serious adverse events for each Part 1 cohort and each Part 2 group. It reports 0 serious adverse events in every listed cohort and group. The associated at-risk counts are 5, 5, 5, 4, and 7 for Part 1 Cohorts 1 through 5, respectively; for Part 2, they are 33 for AMTX-100 CF and 32 for placebo. The record lists 0 deaths in each group.

These figures are counts over the safety record's reported groups and denominators. They are not a comparative statistical test, and the record does not provide confidence intervals for serious events. Zero reported events does not establish that the risk is absent; it means that no serious adverse events are recorded in these groups for the reporting period described. The record does not provide detailed follow-up duration by group, event-level descriptions, or a formal comparison.

The safety denominators differ from the group sizes posted for the primary efficacy outcome. The registry does not explain that difference, so the denominators should be read in the context of the specific safety and efficacy summaries rather than treated as the same analysis population. Serious event counts alone also do not summarize all tolerability information: the registry separately reports other adverse-event counts, but a full assessment requires attention to the event definitions and reporting context.

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

The posted primary outcome describes the percentage meeting a demanding Day 28 responder definition in each Part 2 group. The reported percentage is 3.8% for AMTX-100 CF and 9.7% for placebo. The record does not report an inferential comparison or an interval estimate for these percentages, and it notes missing subjects in both groups. Those omissions make the precision and robustness of the primary comparison difficult to assess from the registry record alone.

The secondary DLQI summary supplies a recalculated unadjusted mean difference, but its interval is broad and includes zero. That result is compatible with a range of group differences in either direction; it does not establish equivalence, and it does not provide a definitive treatment-effect conclusion. The p value is unadjusted and should be considered in light of the multiple listed outcome measures and time points, for which a multiplicity approach is not reported.

The safety record reports no serious adverse events in the listed cohorts and groups, and no deaths. These observations describe the reported safety summaries; they cannot demonstrate that serious events are impossible or fully characterize safety beyond the recorded follow-up and definitions. The registry does not report all details needed to judge the completeness of safety ascertainment.

These results do not establish that AMTX-100 CF works or does not work. They describe what the registry reports for the selected endpoints and what can be inferred from the available summaries. The study had distinct dose-escalation and randomized comparison components, and the primary result pertains to the Phase II comparison rather than the open-label Part 1 cohorts. The registry's missing-data methods, analysis populations, full statistical plan, and primary inferential analysis are not reported. Interpretation should therefore remain bounded by the posted data and their stated limitations.

13. Why This Trial Matters Statistically

This trial illustrates why a registry result should be read by endpoint type and study part rather than as one undifferentiated conclusion. Part 1 was an open-label dose-escalation component focused on the maximum BSA percentage treated and safety; Part 2 was the randomized vehicle-controlled comparison. The primary efficacy endpoint belongs to Part 2, while the five Part 1 cohorts serve a different role. Keeping those components distinct avoids treating dose-escalation observations as if they were randomized comparative evidence.

The primary endpoint is a composite responder rule based on both final status and change from baseline, with rescue treatment counted as non-response. Such definitions affect what a reported percentage means. In this case, the registry gives group percentages but does not provide a confidence interval or inferential comparison, and it notes missing subjects in both groups. That combination makes precision and missing-data handling central to interpretation rather than secondary technical details.

The secondary DLQI result demonstrates the difference between a point estimate and the uncertainty around it. The recalculated mean difference is 9.7, but the interval extends from -22.1 to 41.5. General statistical interpretation relies on both the estimated effect and its uncertainty; an estimate alone can give a misleading impression of certainty. The planning illustrations also show why observed-effect-based sample-size calculations should not be read as evidence that a completed study had adequate power.

Finally, multiple listed measures and time points require attention to multiplicity and prespecification. An unadjusted secondary result has a different evidential status from a prespecified primary analysis. Since the registry does not report the analysis plan or multiplicity procedure, the available results are best treated as bounded summaries rather than a complete confirmatory analysis.

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 immediate limitation is incomplete reporting around the primary endpoint. The registry notes missing subjects in both groups but does not describe the number missing, their reasons, or the approach to analysis. It also does not report an interval estimate or statistical comparison for the primary responder percentages. As a result, the precision of the primary comparison cannot be evaluated from the posted record.

Other analysis details are also absent. The registry does not identify the analysis populations, the primary statistical method, the sample-size justification, interim-analysis plans, or a multiplicity strategy. The study's official title describes double-blinding, while its masking entry says quadruple; the practical procedures used to maintain masking are not described. Randomization and allocation concealment methods are also not reported.

The posted secondary DLQI comparison is a recalculation from summary statistics rather than a reported sponsor analysis. It is unadjusted, and its interval is wide. The registry lists a broader set of secondary measures, but does not provide numerical comparative results for those outcomes in the record described. This limits the ability to assess whether findings were consistent across clinical signs, symptoms, and quality-of-life domains.

Safety and efficacy summaries use different reported group sizes, and the registry does not explain how their populations relate. The serious-event counts are descriptive and lack interval estimates or a formal comparison. In addition, the primary efficacy result is from the randomized Part 2 comparison, whereas Part 1 was open-label dose escalation; evidence from those components should not be combined as though they arose from the same design. These reporting limitations do not prove bias or invalidate the observations, but they restrict how confidently the posted summaries can be interpreted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Topically Applied AMTX-100 CF for Adult Patients With Mild to Moderate Atopic Dermatitis — NCT04313400.
• Registry record last updated 2025-05-02; status last verified 2025-04.
• Results first posted 2025-05-02.
• 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.

18. Record Summary

NCT04313400 is a completed Phase I/II study of topical AMTX-100 CF in adults with mild to moderate atopic dermatitis. It included open-label dose escalation in Part 1 and a randomized vehicle-controlled comparison in Part 2. Overall enrollment was 91, and the registry records study start on 2020-03-10 and primary completion on 2023-12-19.

The primary Part 2 outcome was the Day 28 responder percentage, defined by a vIGA-AD score of 0 or 1 and a reduction of at least 2 points from baseline, with rescue-treated subjects counted as non-responders. The registry reports percentages of 3.8% for AMTX-100 CF and 9.7% for placebo, and notes missing subjects in both groups. A secondary DLQI comparison is available as an unadjusted recalculation from posted summaries; its interval includes zero. The record reports 0 serious adverse events and 0 deaths in each listed group. Missing analysis details, including the primary inferential method, missing-data handling, and multiplicity strategy, limit interpretation.