A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Japanese Subjects With Palmoplantar Pustulosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Japanese Subjects With Palmoplantar Pustulosis (NCT04057937), a randomized phase 2 study. The primary outcome is Percentage of Participants Who Achieve a PPPASI-50 at Week 16.

2. Clinical Question

The registry describes a Phase 2, randomized, double-blind, placebo-controlled, parallel-group study in Japan. Its primary endpoint is a responder outcome: each participant is classified according to whether their PPPASI total score decreased by at least 50 percent from baseline by Week 16. The central comparison is therefore the proportion meeting that threshold in the apremilast and placebo groups, rather than the average score change alone.

The posted Week 16 results report responses for 78.3% of participants in the apremilast group and 40.9% in the placebo group. The registry-reported percentage difference is 37.4, with a 95% confidence interval from 18.6 to 56.1 and p < 0.001. These figures describe the observed comparison in this trial; interpretation depends on the study population, endpoint definition, and uncertainty around the estimate.

3. Trial Design

NCT04057937 is a completed Phase 2 study sponsored by Amgen, with a randomized, quadruple-masked, parallel-group design. The registry lists enrollment of 90 participants and identifies palmoplantaris pustulosis as the condition. The study evaluated apremilast against placebo in Japanese subjects with PPP and an inadequate response to topical steroid and/or topical vitamin D3 derivative preparations.

The placebo-controlled phase lasted 16 weeks. Participants were assigned to matched placebo or apremilast 30 mg twice daily. After that phase, participants who completed it entered an active-treatment phase, during which all received apremilast 30 mg twice daily for up to an additional 16 weeks. The study description states that the final study visit occurred 4 weeks after stopping apremilast. Because the later phase did not retain a placebo group, its treatment experience does not provide the same randomized placebo comparison as the primary Week 16 assessment.

The primary endpoint was assessed at Week 16, at the end of the placebo-controlled phase. The registry identifies the primary analysis population as the intent-to-treat population: all randomized participants who received at least one dose of investigational product. The posted primary outcome lists 44 participants in the placebo group and 46 in the apremilast group. The registry reports a chi-squared analysis for the between-group percentage difference.

The study began on 2019-10-16, had primary completion on 2021-01-18, and is listed as completed. Additional details about randomization procedures, masking roles, allocation concealment, protocol deviations, and the operational conduct of the study are not reported in the registry record. The record identifies quadruple masking but does not specify which groups of people were masked.

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: Participants were randomized in a 1:1 ratio to receive either apremilast or matched placebo from Week 0 to Week 16 (placebo-controlled phase) of the study. Eligible participants then entered an active-treatment phase and received apremilast from after Week 16 to Week 32.

Placebo-controlled Phase

Reasons for not completing this period:

Active-treatment Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) population which includes all randomized participants who received at least one dose of investigational product.

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 of Participants Who Achieve a PPPASI-50 at Week 16, measured over At Week 16.

The primary endpoint is the percentage of participants who achieved PPPASI-50 at Week 16. PPPASI-50 is defined as a decrease of at least 50 percent in the PPPASI total score from baseline. This converts change in a disease severity score into a responder classification: each participant either meets the stated threshold or does not.

PPPASI is a disease-specific assessment of erythema, pustules or vesicles, and desquamation or scale on the palms or soles. These signs are scored as sub-scores and summed into a total score ranging from 0 to 72; a higher score indicates more severe disease. The registry describes PPPASI as an efficacy assessment tool for PPP.

A threshold-based endpoint can be useful because it expresses change in terms of the proportion reaching a defined level of improvement, rather than only reporting an average change. It also makes the group comparison interpretable as a difference in response percentages. However, classification at a threshold does not show how far participants who met it exceeded the threshold, or how close nonresponders came to it. The continuous PPPASI score changes are therefore relevant complementary outcomes, but they answer a different question from the primary responder endpoint.

The primary endpoint was assessed at Week 16, during the placebo-controlled phase. The registry does not report a confidence interval for each arm's response percentage separately; it reports an interval for the between-group percentage difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a responder proportion, and the registry reports a chi-squared analysis of the percentage difference between apremilast and placebo. This is a categorical comparison: participants are classified by whether they achieved PPPASI-50, and the analysis compares the resulting response percentages. The registry reports a percentage difference of 37.4, a 95% confidence interval from 18.6 to 56.1, and p < 0.001.

What does the confidence interval express?

General explanation: a confidence interval describes the uncertainty around an estimated quantity under the model and sampling assumptions used for the analysis. A narrower interval indicates greater precision than a wider interval on the same scale. The interval applies to the between-group percentage difference, not to individual outcomes and not to the separate arm percentages. Its lower and upper limits are both positive, so the interval is consistent with a positive difference under the reported method.

How should the p-value be read?

General explanation: a p-value measures how unusual data at least as inconsistent with a stated null model would be if that model were true, subject to the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The posted p-value is < 0.001 for the reported primary comparison. The record names the chi-squared method but does not provide further details about the implementation or any covariate adjustment.

How do the continuous secondary outcomes differ?

The registry reports least-squares mean changes and standard errors for the Week 16 PPPASI and PPSI total score outcomes. A least-squares mean is a model-based mean; the record does not report enough modeling detail to fully describe the adjustment or specification used. A standard error describes the estimated precision of a mean, rather than the spread of individual observations. The simple comparisons accompanying these outcomes are marked as recalculated and use approximate standard deviations derived from the posted summary statistics. They are unadjusted re-calculations, not replacements for a sponsor-reported model.

For change from baseline in PPPASI total score, the posted least-squares means were -11.03 for placebo and -16.48 for apremilast, with standard errors of 1.26 and 1.224. The unadjusted recalculated mean difference was -5.45, with a 95% interval from -8.893 to -2.007 and p = 0.002. For change from baseline in PPSI total score, the posted least-squares means were -2.56 and -4.19, with standard errors of 0.303 and 0.293. The unadjusted recalculated mean difference was -1.63, with a 95% interval from -2.456 to -0.804 and p < 0.001. These calculations use the posted summary statistics and an approximate standard deviation, so they should be interpreted as simple comparisons rather than as the trial's full model-based analysis.

What do the planning illustrations mean?

General explanation: a power calculation estimates the sample size needed to detect a specified effect under stated assumptions. The registry's planning illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation. They consider effects set at 100%, 75%, and 50% of the observed effect. For the PPPASI continuous comparison, the listed participants per arm for 80% power are 36, 64, and 142 across those effect assumptions; for 90% power they are 48, 85, and 190. For the PPSI continuous comparison, the corresponding figures for 80% power are 23, 41, and 92, and for 90% power are 31, 55, and 123.

These figures are planning illustrations based on observed effects, not evidence of the trial's original design assumptions and not observed power. The trial's own sample-size justification is not reported in the registry record. The illustrations also depend on the stated assumptions, including equal allocation and a normal approximation; they are not guarantees that a future study would detect an effect.

What statistical details remain unclear?

The registry does not report the sample-size justification, a full statistical analysis plan, interim analyses, the missing-data method, or the handling of protocol deviations in the primary analysis. It also does not report a multiplicity adjustment for the secondary outcomes. These omissions do not change the posted numerical results, but they constrain assessment of how analyses were selected, how incomplete observations were treated, and how much weight to give multiple secondary comparisons.

10. Analyses Reported by the Sponsor

The primary comparison is reported in the registry as a chi-squared analysis: the percentage difference between apremilast and placebo was 37.4, with a 95% confidence interval from 18.6 to 56.1 and p < 0.001. The primary outcome also reports the arm response percentages, 78.3% and 40.9%, respectively. These are the sponsor-reported primary results and should be distinguished from simple re-calculations of other outcomes.

The continuous PPPASI and PPSI comparisons are unadjusted re-calculations from the posted least-squares means and standard errors. Their approximate standard deviations are reconstructed from those summary statistics, so the resulting comparisons may not reproduce the trial's underlying model or its assumptions. The registry lists no sponsor-reported analyses for those secondary comparisons. Their p-values and intervals are therefore useful as simple descriptive comparisons, but they carry less authority than a fully reported analysis from the study's statistical plan.

No discrepancy is flagged between the posted primary result and a recalculation. The registry's primary analysis remains the appropriate reference for the primary endpoint; the recalculated secondary comparisons are supplementary and should not be presented as the sponsor's own model results.

11. Multiplicity, Missing Data and Analysis Populations

The registry defines the primary analysis population as the intent-to-treat population, including all randomized participants who received at least one dose of investigational product. The posted primary outcome lists 44 participants for placebo and 46 for apremilast. The record does not report a separate description of how the analysis population was constructed in practice, whether participants were excluded after randomization, or how deviations from assigned treatment were handled.

Missing-data handling is not reported in the registry record. In particular, the record does not state how participants without a Week 16 PPPASI assessment were treated in the responder analysis, whether any values were imputed, or what sensitivity analyses were conducted. The arm counts alone do not establish how missing measurements affected the estimates. Without those details, the robustness of the primary result to missing outcomes cannot be evaluated from the registry information.

The record lists multiple secondary outcomes, including repeated responder assessments, score changes, and area-under-the-curve measures. A plan specifying a testing hierarchy or adjustment for multiple comparisons is not reported in the registry record. General explanation: if many statistical tests are considered without a prespecified strategy, some apparently strong results may arise by chance even when the underlying effects are absent. This is why unadjusted secondary findings are usually interpreted as supportive or exploratory rather than as equivalent to a single primary test.

The registry reports one primary analysis using a chi-squared method. Further details of the statistical analysis plan, interim analyses, and the sponsor's procedures for handling missing data are not reported in the registry record. The absence of these details does not show that the procedures were not used; it means their use and implications cannot be assessed from the record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: constipation (1.1%), volvulus (1.1%), covid-19 pneumonia (1.1%), peritonitis (1.1%).

During the placebo-controlled phase, the registry reports serious adverse events affecting 0 of 44 participants in the placebo group and 0 of 46 participants in the apremilast group. In the active-treatment phase, 3 of 87 participants receiving apremilast were reported as affected by serious adverse events. No deaths were reported in any of the listed groups. These are counts for the phases and denominators stated in the registry; they are not a direct comparison of randomized groups across the full study because all participants in the active-treatment phase received apremilast.

The registry lists constipation, volvulus, COVID-19 pneumonia, and peritonitis among the serious adverse event terms, each reported as 1.1%. These terms should be read as registry-listed events, not as a complete account of the nature, timing, duration, or relationship of events to treatment. The record does not report additional detail about adjudication or causal attribution.

The counts do not establish that a treatment is safe or unsafe. In particular, a count of zero in a group does not prove that an event cannot occur, and counts from groups observed during different study phases are not interchangeable. Interpretation of overall safety also requires the full adverse-event profile and exposure context, which are not captured by the serious-event counts alone.

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

The posted Week 16 results show a higher PPPASI-50 response percentage in the apremilast group than in the placebo group within this randomized, placebo-controlled trial. The reported percentage difference is 37.4, and its 95% confidence interval ranges from 18.6 to 56.1. The p-value of < 0.001 describes the primary comparison under the reported chi-squared method. Together, these statistics characterize the direction, size, and uncertainty of the group-level result.

This result does not predict the outcome for an individual participant. The endpoint records whether a participant crossed a specified score-change threshold; it does not describe each person's complete symptom experience, nor how much improvement occurred for responders or nonresponders. The continuous score outcomes provide a different summary of change and should be considered alongside, not substituted for, the primary responder outcome.

The result applies to the trial population and design: Japanese subjects with PPP and an inadequate response to specified topical treatments, randomized to apremilast or placebo during the placebo-controlled phase. It does not by itself establish how the result would generalize to people outside that population, other treatment settings, or longer-term comparisons. After Week 16, both groups could receive apremilast, so the subsequent active-treatment period does not preserve a concurrent placebo comparison.

Statistical evidence of a group difference is not the same as evidence of clinical importance. The registry does not report a benchmark for what size of difference would be considered clinically important. Nor do the primary estimates address every outcome that may matter to participants. The record's omissions concerning missing-data handling, multiplicity, and detailed analysis methods also limit independent assessment of robustness. The most direct conclusion is about the reported Week 16 comparison, not a broader claim about all potential benefits, risks, or longer-term outcomes.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint definition matters in clinical statistics. The primary outcome is not simply a change in a severity score; it is the proportion of participants meeting a predefined PPPASI-50 threshold. That choice makes the result accessible as a responder percentage, while also discarding detail about the magnitude of score change on either side of the threshold. The continuous secondary measures answer a related but distinct question.

The trial also demonstrates the value of reporting both an effect estimate and its uncertainty. The percentage difference is accompanied by a 95% confidence interval, which gives more information than a p-value alone about the range of values compatible with the analysis. At the same time, a statistically notable result cannot determine clinical importance without an interpretable benchmark, which is not reported in the record.

Its treatment sequence matters for inference. Randomization supports the placebo-controlled comparison through Week 16, while the later phase gives all participants apremilast. That later experience cannot function as a continuing placebo-controlled comparison. Recognizing this boundary prevents readers from treating results across different phases as if they arose from the same randomized contrast.

Finally, the record highlights why transparent reporting of missing-data methods, multiplicity decisions, and analysis plans is important. These details help readers assess whether estimates are sensitive to incomplete observations and how secondary findings should be weighed. Planning illustrations based on observed effects can inform future study design, but they are not the original sample-size rationale and do not measure the probability that this completed trial detected an effect.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record gives limited detail about several design and analysis features needed for a full statistical appraisal. Although it identifies the study as randomized and quadruple-masked, it does not report the randomization procedure, allocation concealment, which roles were masked, or how masking was maintained. A sample-size justification, including the target effect and assumptions used in the original design, is not reported in the registry record.

Missing-data methods and sensitivity analyses are not reported. This matters for a Week 16 responder outcome because participants without an assessment may affect the denominator or require a specified analysis approach. The available arm sizes do not explain how incomplete observations were handled. The record also does not describe protocol deviations or provide enough detail to evaluate whether the analysis population differed from the randomized population.

The registry reports the primary chi-squared method but does not provide a full statistical analysis plan, including possible covariate adjustments or detailed outcome coding. It does not report a multiplicity strategy for the many secondary outcomes. Only two secondary continuous Week 16 outcomes have summary statistics and simple re-calculations in the posted results; analyses for the other listed secondary measures are not reported in the registry record.

Generalizability is also bounded by the stated study population: Japanese subjects with PPP and an inadequate response to specified topical preparations. The primary comparison ends at Week 16, after which the placebo group could receive apremilast. The later phase therefore cannot supply a continuing randomized comparison with placebo. These limitations shape interpretation of the posted results; they do not, by themselves, establish that the analyses were improperly conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Japanese Subjects With Palmoplantar Pustulosis — NCT04057937.
• Registry record last updated 2024-07-17; status last verified 2024-07.
• Results first posted 2022-01-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT04057937 is a completed Phase 2 randomized, quadruple-masked, parallel-group study of apremilast in Japanese subjects with palmoplantar pustulosis. The placebo-controlled phase compared apremilast 30 mg twice daily with matched placebo for 16 weeks, followed by an active-treatment phase in which participants received apremilast.

The primary endpoint was PPPASI-50 at Week 16. The registry reports response percentages of 78.3% for apremilast and 40.9% for placebo, with a percentage difference of 37.4, a 95% confidence interval from 18.6 to 56.1, and p < 0.001. The primary analysis used a chi-squared method.

The record lists 11 secondary outcomes, but detailed results are available for only two continuous Week 16 comparisons in the posted data. Those comparisons are simple unadjusted re-calculations. Missing-data handling, multiplicity procedures, and the trial's sample-size justification are not reported in the registry record. Serious adverse event counts and deaths are reported separately for the placebo-controlled and active-treatment phases and should be interpreted in light of those different study periods.