A Study to Test Long-term Treatment With Spesolimab in People With Palmoplantar Pustulosis (PPP) Who Took Part in Previous Studies With Spesolimab: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test Long-term Treatment With Spesolimab in People With Palmoplantar Pustulosis (PPP) Who Took Part in Previous Studies With Spesolimab (NCT04493424), a na phase 2 study. The primary outcome is Number of Subjects With Treatment Emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, single-group study of spesolimab for people with palmoplantar pustulosis who had participated in previous spesolimab trials. The registry identifies Boehringer Ingelheim as the sponsor. The study began on 2020-09-04, had a primary completion date of 2023-01-16, and is listed as terminated. The reason for termination is not reported in the registry record.

The registry records enrollment of 108 participants. The brief description says participants could remain in the study for up to 5 years and visited the study site every month for under-the-skin injections and assessments. The treatment group description specifies up to 260 weeks. The primary endpoint timeframe runs from the first administration of study drug until the last administration plus 112 days, with the stated maximum timeframe of up to 869 days. These descriptions refer to different aspects of the study and do not establish that every participant received treatment or follow-up for the maximum duration.

There was no random allocation to alternative treatments and no masking. In a single-group extension study, participants receive the study treatment, so safety observations can be described during treatment, but there is no concurrent untreated or alternative-treatment group for estimating a comparative effect. Prior participation and prior response to spesolimab also define a selected group; the record does not describe the population as representative of all people with PPP.

The registry lists secondary outcomes based on PPP ASI change and response, and on the proportion with a PPP PGA rating of clear or almost clear, at specified follow-up points relative to the parent trial baseline. These listed outcomes describe planned measures, not evidence of a particular outcome. The registry record does not report the study’s rationale for its enrollment target or further details of its protocol beyond the described design.

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: All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Treated Set for Maintenance Treatment (TS-MT): This patient set included all patients who received at least one dose of the maintenance treatment 600 mg s.c. every 4 weeks.

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.

Population: The safety analysis set for maintenance treatment (SAF-MT): Included all patients who received at least one dose of the maintenance treatment Spesolimab (BI 655130).

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Treatment Emergent Adverse Events (TEAEs), measured over From first administration of study drug until last administration of study drug + 112 days, up to 869 days..

The primary endpoint is the number of participants with treatment-emergent adverse events (TEAEs). It is a participant count: it concerns how many people experienced at least one event, not the total number of event episodes. The registry defines the relevant period as the interval from the start of treatment in the extension trial through the end of the residual-effect period. It also classifies an adverse event that began before the first extension-trial dose as treatment-emergent if it worsened during extension treatment.

Safety endpoints of this kind are used to describe health problems recorded during exposure to a study treatment. They help characterize what was observed in the treated group and over the stated observation period. They do not, by themselves, establish that the treatment caused an event: events can occur for reasons unrelated to treatment, and a single-group study cannot compare event frequency with a concurrent control group.

The primary endpoint population is the Treated Set for Maintenance Treatment. The record defines this set as patients who received at least one dose of maintenance spesolimab 600 mg under the skin every 4 weeks. The event count should therefore be interpreted in relation to the specified treated population and event window, not as a general estimate for every person with PPP or for other treatment settings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count describe?

General statistical explanation: a count of participants with an event records how many people experienced the event at least once during the defined observation period. It is different from a count of event episodes, because one participant can experience more than one event. Counts are easiest to interpret when their population and observation period are clear. In this trial, the primary endpoint is explicitly framed as the number of subjects with TEAEs, and its period is defined from the first administration through the end of the residual-effect period.

The registry’s definition also includes a worsening rule: an event that started before the first extension-trial dose can count as treatment-emergent if it deteriorated during extension treatment. This means the endpoint is not limited to newly starting health problems. It reflects the stated operational definition, which is important when interpreting the event count.

Why does the study design matter?

General statistical explanation: a randomized comparison can help distinguish differences associated with treatments from differences that arise because groups have different background characteristics. A single-group study has no such concurrent contrast. Its observed safety counts can describe events in the group, but cannot estimate a treatment-versus-control difference. Open-label treatment also means that treatment assignment is known; the registry lists no masking.

Because this was an extension trial for people who took part in earlier spesolimab studies, the participants were selected through prior study participation. The brief description further indicates that people who benefited from previous spesolimab treatment could join. This limits how broadly the observations can be generalized. The registry does not report a comparison with people who had not previously received spesolimab.

How should the at-risk group be read?

The safety summary lists 108 participants at risk for the serious-event category and 108 for the other-event category. The primary endpoint population is defined separately as the Treated Set for Maintenance Treatment, consisting of patients who received at least one dose of the specified maintenance regimen. The record does not establish in the endpoint description that every enrolled participant necessarily belongs to that treated set, so the enrolled total and the endpoint population should not be treated as interchangeable without further detail.

General statistical explanation: an at-risk denominator tells the reader how many participants were considered in the relevant event summary. It does not convey how long each person was observed. If follow-up time varies, a raw count does not account for those differences. The registry gives an overall maximum timeframe for the endpoint but does not report participant-level time at risk or a rate analysis.

What can event percentages and terms tell us?

The serious-event list includes the reported terms and percentages, such as Fall at 1.9% and several terms at 0.9%. These are descriptive summaries, not evidence that the events were caused by the study treatment. The registry record does not describe an adjudication process, provide individual case details, or report a causal assessment for each term. Multiple event terms may also occur in the same participant, so terms should not automatically be interpreted as distinct people.

General statistical explanation: a confidence interval expresses the uncertainty around an estimate under specified assumptions. The record does not report confidence intervals for these safety counts or percentages. Without interval estimates, the summary does not quantify the sampling uncertainty around the reported values. Even a confidence interval would not solve the absence of a concurrent control group or establish causation.

What can the listed outcome analyses establish?

The registry lists 4 outcome measures and 0 analyses. The secondary outcomes refer to PPP ASI change and response, and PPP PGA clear or almost clear status, at follow-up points compared with baseline in parent trial NCT04015518. The registry record does not provide analysis results for those outcomes in the information recorded. The listed measures should therefore be distinguished from reported findings.

General statistical explanation: a statistical analysis plan specifies how outcomes, missing observations, and multiple tests will be handled. Those choices can affect interpretation, especially when a study assesses several outcomes. The registry record does not report the detailed analysis plan, missing-data methods, or multiplicity adjustment. Their absence from the record does not establish that no methods were used; it means those methods are not reported in the registry record.

Any sample-size calculation used for planning is not a measure of the evidence observed in a completed study. General statistical explanation: power is a design property tied to a specified hypothesis, effect, variability, and analysis, and it should not be inferred retrospectively from an observed result. The record does not report a trial-specific sample-size justification or a comparative hypothesis for this single-group safety study. Planning illustrations should not be described as observed power or as proof that the study could detect a treatment effect.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Spesolimab (BI 655130)")
n      <- c(108)
events <- c(96)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Spesolimab (BI 655130)  108  96  88.9  81.4  94.1  81.6  93.5  81.6  93.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 4 outcome measures, including the primary TEAE count and secondary PPP severity measures. The secondary measures include percent change in PPP ASI from the parent-trial baseline at Weeks 48 and 96, the proportion with PPP ASI50 at Weeks 48 and 96, and the proportion with PPP PGA of 0 (Clear) or 1 (Almost Clear) at Week 48 and 96. The record lists 0 analyses. It does not report results for these measures in the information recorded.

When a study examines multiple outcomes or time points, the chance of obtaining at least one apparently notable result can depend on how many comparisons are made and how they are interpreted. General statistical explanation: multiplicity procedures can control the overall error rate or otherwise clarify which outcomes are confirmatory and which are exploratory. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed statistical analysis plan. It is therefore not possible to determine from the record how multiplicity was addressed.

The record also does not report the method used to handle missing outcome observations, withdrawals, or differing follow-up. That information matters because missingness can affect which participants contribute to each outcome and how representative the available observations are. No assumptions about missing data or sensitivity analyses should be inferred from the endpoint description alone.

The primary endpoint population is defined as the Treated Set for Maintenance Treatment, including patients who received at least one dose of the specified maintenance treatment. The record does not provide a full accounting of how many participants contributed to each listed outcome or whether the same analysis population was used for all measures. The enrollment count and the endpoint population definition are not sufficient to establish the completeness of outcome data or the analysis populations for secondary measures.

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: fall (1.9%), cardiac failure chronic (0.9%), tricuspid valve incompetence (0.9%), hypertrophic cardiomyopathy (0.9%), colitis (0.9%).

The registry’s serious adverse-event summary lists 108 at risk and 19 affected in the spesolimab group. It separately lists 108 at risk and 77 affected in the other adverse-event category, and reports 0 deaths. These are counts for the categories in the registry summary; they are not counts of event episodes and should not be added together to create a total, since participants may appear in more than one category. The record does not provide enough detail to determine overlap.

The serious-event terms reported are Fall at 1.9%, Cardiac failure chronic at 0.9%, Tricuspid valve incompetence at 0.9%, Hypertrophic cardiomyopathy at 0.9%, Colitis at 0.9%, and Large intestine polyp at 0.9%. These terms and percentages are descriptive entries. The record does not provide case narratives, timing for each event, or a treatment-causality assessment for these terms.

General statistical explanation: safety summaries describe events observed in the defined study population and observation window. They do not on their own distinguish events caused by treatment from events that would have occurred for other reasons. That distinction is especially important in a single-group study with no concurrent control. The counts also do not account for varying individual follow-up time. The registry does not report time-adjusted rates or confidence intervals for the safety summary.

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

The results describe adverse events recorded among participants in an open-label extension study of spesolimab for PPP. The primary outcome is the number of participants with treatment-emergent adverse events, using a definition that includes new events during the extension and some pre-existing events that worsened during extension treatment. The registry also reports serious-event counts, other adverse-event counts, deaths, and selected serious-event terms with percentages.

These observations can help characterize the kinds of events recorded during treatment in the study group and over the stated event window. They are relevant to the participants who entered this extension study, including the prior-study participation and prior-treatment context. They do not automatically describe all people with PPP, nor do they establish what would happen with another treatment or without treatment.

The study’s single-group design is central to interpretation. Without a concurrent comparison group, the observed counts cannot determine whether spesolimab increased or decreased the occurrence of events relative to an alternative. The counts also cannot establish that a listed event was caused by treatment. The registry record does not report causal assessments, comparative analyses, or confidence intervals for the safety figures.

The registry lists secondary measures of PPP severity at specified follow-up times, but the record information does not report analyses for those measures. Their presence as listed outcomes is not itself evidence of improvement or worsening. Similarly, the terminated status and completion date do not explain why the study ended; that reason is not reported in the registry record.

In statistical terms, the reported safety counts are descriptive evidence from a selected treated group. They should be interpreted alongside the study’s population, event definitions, observation period, and lack of a control arm. They are not a standalone estimate of causal risk, a comparison of treatment strategies, or a conclusion about clinical benefit.

14. Why This Trial Matters Statistically

Extension studies address a different statistical question from randomized comparisons. Their value can include documenting events observed during continued treatment and collecting longer-term observations in people who have participated in earlier studies. In this trial, the primary endpoint and its event window make the safety focus explicit, while the listed secondary outcomes track PPP severity relative to the parent-trial baseline.

The design also illustrates why interpretation depends on the target population. Participants came from earlier spesolimab studies, and the brief description says those who benefited from previous treatment could join. That context may make the extension relevant to continued treatment among prior participants, but it also means the study group is selected. Results should not be assumed to apply to all people with PPP or to people with no prior spesolimab exposure.

The distinction between describing and comparing is especially important. Counts such as 19 participants affected by serious adverse events and 0 deaths provide concrete observations in the registry summary, but the single-group design cannot supply a concurrent counterfactual. Statistical care means reporting those observations without turning them into a treatment-attributable risk or a comparative conclusion.

The record also makes visible the limits of registry-level interpretation. It identifies a defined endpoint, a treated population, outcome measures, and a maximum stated observation period, yet does not report an analysis plan, missing-data methods, multiplicity handling, or results for the listed secondary outcomes. Recognizing both the available safety description and the gaps in analytic detail is essential when reading an extension trial.

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.

Several limitations specific to this study affect interpretation. It was open-label and single-group, with no randomized comparator. As a result, the safety counts describe participants receiving spesolimab but cannot estimate a comparative difference or separate treatment effects from background events. The registry record does not report a reason for the study’s terminated status.

The population was drawn from people who had taken part in previous spesolimab studies; the brief description says people who benefited from prior treatment could join. This selection limits generalization beyond that extension population. The record does not provide detailed participant characteristics or explain how prior participation and prior response affected the enrolled group.

The endpoint is defined over a treatment and residual-effect period, with a stated maximum timeframe of up to 869 days. The study description also says participants could be in the study for up to 5 years and the treatment group was described as up to 260 weeks. These are stated maximums, not evidence that each participant was observed for those durations. Individual follow-up and time at risk are not reported in the registry record.

The record provides safety counts and selected event terms, but does not report confidence intervals, time-adjusted event rates, detailed case information, or causal assessments for the listed events. It also does not report methods for missing data, multiplicity, or the full analysis populations for secondary outcomes. The record lists 0 analyses, and does not report results for the listed PPP severity measures. These limits preclude stronger inference from the registry description alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Test Long-term Treatment With Spesolimab in People With Palmoplantar Pustulosis (PPP) Who Took Part in Previous Studies With Spesolimab — NCT04493424.
• Registry record last updated 2025-10-20; status last verified 2025-10.
• Results first posted 2024-03-20.
• 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

NCT04493424 is a Phase 2, open-label, single-group study of spesolimab in people with PPP who participated in previous spesolimab trials. The registry lists Boehringer Ingelheim as sponsor, enrollment of 108, a start date of 2020-09-04, primary completion on 2023-01-16, and status as terminated. The reason for termination is not reported in the registry record.

The primary endpoint is the number of participants with treatment-emergent adverse events, assessed from first study-drug administration through the end of the residual-effect period, up to 869 days. The safety summary reports 19 participants affected by serious adverse events, 77 in the other adverse-event category, and 0 deaths, with 108 at risk in each listed category.

The registry lists secondary PPP severity outcomes but reports 0 analyses. It does not report a detailed statistical plan, missing-data methods, multiplicity handling, or a reason for termination. The single-group design supports descriptive interpretation of recorded events, not a controlled estimate of treatment effect or causation.