Spesolimab (BI 655130) Single Dose in Generalized Pustular Psoriasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Spesolimab (BI 655130) Single Dose in Generalized Pustular Psoriasis (NCT02978690), a na phase 1 study. The primary outcome is Percentage of Patients With Adverse Reactions, Defined as Drug-related Adverse Events (AE).

2. Clinical Question

The study also lists secondary measures of GPP severity, fatigue, pain, and spesolimab concentrations. These include change or status at Week 2 for several clinical measures and pharmacokinetic measures for drug concentration. The registry record does not report numerical results for those listed measures in the record summarized for this analysis.

Statistically, this is a descriptive question about observations after exposure in a small, single-group study, rather than a comparative question about differences between randomized groups. The study can describe events recorded among participants who received the medication, but without a comparator it cannot isolate how much of any observed event rate is attributable to spesolimab rather than other causes. The open-label design also means that treatment and outcome assessment were not masked, as the registry lists masking as none. These design features shape what the results can establish, independently of the direction of any numerical outcome.

3. Trial Design

The registry identifies NCT02978690 as a Phase I, multicentre, open-label, single-arm study of spesolimab in active generalized pustular psoriasis. Its official title describes investigation of safety, tolerability, pharmacokinetics, pharmacogenomics, and efficacy following a single intravenous dose. The study is listed as completed. The registry records a start date of 2016-12-19 and a primary completion date of 2017-09-20.

Seven participants were enrolled. The study has one treatment group and no randomized allocation or masking. The intervention is spesolimab, and no control arm is described. In a single-group study, measurements after treatment are observed within the treated group; there is no concurrent group to show what would have happened over the same period without the intervention or with a different intervention. This is especially important when interpreting symptoms and adverse events, which may change for reasons other than the treatment under study.

The primary endpoint is the percentage of patients with adverse reactions, defined as drug-related adverse events, through 140 days after administration. Its stated population is the Treated Set, defined as all patients who entered the trial and received trial medication on Day 1 (Visit 3). The registry also lists secondary outcomes for GPPASI total score, GPPGA status, FACIT-Fatigue score, pain VAS score, and pharmacokinetic measures of spesolimab. Several clinical measures are specified at Week 2. The listed outcomes and time points identify what was intended to be assessed, but do not by themselves provide observed results.

The registry record does not report the dose amount, detailed eligibility criteria, the protocol’s sample-size justification, or a statistical analysis plan. It does not report a comparator or details of interim analyses. The study description says it was intended to assess safety, tolerability, pharmacokinetics, pharmacogenomics, and efficacy; the extent of results available for each objective is not reported in the registry record. These omissions limit what can be reconstructed about conduct and analysis from the registry information.

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: This exploratory, Phase I, multi-centre, multi-national trial in male and female patients with a flare of Generalised Pustular Psoriasis (GPP) applied an open-label design.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Treated Set (TS): All patients who entered the trial and received the trial medication on Day 1 (Visit 3).

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: Full Analysis Set (FAS): All patients in the treated set (TS) who had a baseline and at least one post baseline GPP Area and Severity Index (GPPASI) or GPP Physician Global Assessment (GPPGA) measurement and no important protocol violation flagged for exclusion from the FAS.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients With Adverse Reactions, Defined as Drug-related Adverse Events (AE), measured over Up to 140 days from the administration of spesolimab..

The primary endpoint is the percentage of patients with adverse reactions, with adverse reactions defined as drug-related adverse events. The stated observation period is up to 140 days from administration of spesolimab, and the endpoint population is the Treated Set: patients who entered the trial and received trial medication on Day 1 (Visit 3).

An event percentage is a descriptive way to express how often an event occurred among the people at risk of being observed. The drug-related qualification is important: it distinguishes events considered related to the study medication from adverse events more generally. The registry record does not report how relatedness was assessed, who made that assessment, or the numerical result for this primary endpoint. Therefore, the event counts recorded elsewhere in the safety information should not automatically be treated as the primary endpoint result.

Safety is a central concern in a Phase I study, and recording adverse events can characterize what was observed after exposure. However, a single-group event percentage does not establish that the medication caused an event. Without a concurrent comparator, background illness, other circumstances, and chance are not separated from treatment effects. Also, a small study can describe only a limited number of observations, and the precision of an event-rate estimate depends on the number of participants and the number of events. No confidence interval for the primary endpoint is reported in the registry record.

The listed time window gives context for which events could count toward the endpoint, but the registry does not provide event timing or endpoint-level details. Thus, the endpoint definition is clear enough to identify the intended safety question, while the posted information does not permit a numerical estimate of the primary endpoint itself.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish what an endpoint measures from what can be inferred from its observed value. The registry record identifies the primary outcome as a percentage of patients with drug-related adverse events, but does not report a numerical outcome estimate or a statistical analysis plan. The explanations below are general statistical context, not a description of unreported protocol procedures.

What does an event percentage represent?

General: An event percentage describes the share of an observed group that experienced a specified event over a defined observation period. The event definition, population, and time window all matter. Here, the stated primary definition is a drug-related adverse event, the population is the Treated Set, and the timeframe is up to 140 days from administration. A count of all adverse events is not necessarily the same as a count meeting the endpoint’s drug-related definition. The registry does not give the primary percentage, so it is not possible to interpret its size or precision.

General: A percentage is an estimate based on a finite group. With few observations, each person’s status has substantial influence on the estimate, and uncertainty can be wide. A confidence interval is a range of values compatible with the observed data under a specified statistical method. It communicates uncertainty around an estimate; it is not a guarantee that the true value lies in that range. No confidence interval for the primary endpoint is reported in the registry record.

Why does the single-group design matter?

General: A one-group study can describe events and measurements among treated participants. It cannot directly compare outcomes with a concurrent control group. In a randomized controlled trial, random assignment can help balance measured and unmeasured factors between groups on average. That comparison is unavailable because the registry lists a single group, no allocation, and no masking. Changes in symptoms or event occurrence over time could reflect the disease course, other influences, measurement, or treatment; a within-group observation cannot separate those explanations on its own.

Open-label means that the study was not masked. General: Knowledge of treatment can influence reporting, decisions to investigate an event, or subjective assessments. This does not mean that bias necessarily occurred; it means that interpretation should account for the possibility. The registry record does not describe procedures for event attribution or outcome assessment in enough detail to evaluate those issues further.

What do the safety counts tell the reader?

The registry records 0 serious adverse events among 7 at risk, 7 other adverse events among 7 at risk, and 0 deaths. These counts are descriptive. General: A count can summarize what was recorded, but by itself does not identify causation, severity beyond the category used, duration, or recurrence. The term “other” is not further defined in the record, and the primary endpoint is narrower because it specifies drug-related events. The registry also does not report the primary endpoint result or serious-event terms, which prevents a fuller endpoint-level account.

How should the planning calculations be understood?

General: A sample-size calculation asks how many observations may be needed under specified assumptions to detect an effect with a chosen statistical procedure. It is a planning tool, not a result. The study’s stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; its target effect is described as a fraction of the observed effect. Those assumptions define a hypothetical two-arm calculation. They do not describe the single-group study that was conducted and should not be read as observed power. The protocol’s own sample-size justification is not reported in the registry record.

General: Power is a design property under assumed effect and variability, not a retrospective measure of whether a study “worked.” A small sample may make estimates imprecise, even when no serious events are observed. Conversely, a planning calculation cannot establish that a result is reliable or clinically meaningful. No numerical planning results are reported in the registry record available for this analysis, so no participant-per-arm target can be interpreted.

What cannot be assessed from the record?

The registry record lists no analysis results, and it does not describe the statistical methods used to analyze the primary or secondary outcomes. It does not report confidence intervals, model choices, or details about handling repeated measurements. General: Such details matter because different methods can account for uncertainty and repeated observations differently. No particular method should be attributed to this study without a report of its use.

The study lists pharmacokinetic outcomes, including area under the concentration-time curve and maximum measured plasma concentration. General: Pharmacokinetic summaries describe drug exposure and observed concentration patterns; their interpretation depends on sampling times, assay methods, and analysis choices. Those details and the numerical results are not reported in the registry record. The registry also states that pharmacogenomics was among the study objectives, but does not provide a result or analysis description for that objective. Thus, the registry supports identification of intended methods questions, but not reconstruction of the analyses performed.

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")
n      <- c(7)
events <- c(4)
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  7  4  57.1  18.4  90.1  25.0  84.2  24.5  84.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes: a primary safety endpoint and secondary measures covering disease severity, global assessment, fatigue, pain, and pharmacokinetics. It does not report an analysis plan explaining whether or how the secondary outcomes were prioritized, whether any adjustment for multiple comparisons was planned, or how results across outcomes were to be interpreted. Such multiplicity procedures are not reported in the registry record.

General: When many outcomes or comparisons are examined, the chance of at least one apparently notable finding can increase. A prespecified hierarchy or multiplicity adjustment can help control how results are interpreted. Without a stated plan and reported analyses, it is not possible to determine whether findings were confirmatory, exploratory, adjusted, or selected after examination of the data. The record lists 0 analyses, and no numerical inferential results are reported for the outcomes described in this analysis.

The registry defines the primary endpoint population as the Treated Set: patients who entered the trial and received medication on Day 1 (Visit 3). The safety record lists 7 participants at risk in both serious and other adverse event categories. However, the record does not describe missing observations, exclusions from specific analyses, or the handling of incomplete outcome data. Whether any measurements were missing, and how any such missingness was treated, is not reported in the registry record.

General: Missing data can affect interpretation when the likelihood of missingness is related to health status, treatment, or the outcome itself. Different assumptions and methods can yield different estimates. No particular missing-data method or assumption should be attributed to this study because it is not reported. The registry also does not give details about analysis populations for the secondary outcomes or pharmacokinetic measures. This limits assessment of whether the populations contributing to different outcomes were consistent.

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 non-serious adverse event terms

The registry safety counts list 7 participants at risk for serious adverse events and 0 with a serious adverse event. It lists 7 participants at risk for other adverse events and 7 with an event in that category. Deaths are recorded as 0. These are event counts in a study group, not comparative estimates.

The serious adverse event count should be read as a description of what was recorded among the participants at risk during the relevant safety observation, not as proof that serious events are impossible or that risk is absent. The study enrolled 7 participants, so the data are limited in scale. The registry does not report the serious-event terms; its list of top serious terms is empty. It also does not provide event timing or detailed severity information for the other adverse events in the record.

The primary endpoint is the percentage with drug-related adverse events through 140 days, whereas the safety counts distinguish serious events from other events. The record does not establish that all other adverse events were judged drug-related, so the 7 participants with other adverse events should not be substituted for the primary endpoint result. That primary numerical result is not reported in the registry record.

General: An adverse event occurring after treatment is not automatically caused by treatment. A single-group study has no concurrent comparator to help distinguish treatment-related events from background events. The event counts are useful as descriptive safety observations, but they do not determine causation or provide a precise estimate of risk.

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

The study’s stated purpose was to assess safety, tolerability, pharmacokinetics, pharmacogenomics, and efficacy after a single intravenous dose of spesolimab in adults with active GPP. The registry identifies a completed Phase I, open-label, single-group study with 7 participants enrolled. The information therefore describes a small early-phase investigation rather than a randomized comparison.

The safety record reports 0 serious adverse events among 7 at risk, 7 other adverse events among 7 at risk, and 0 deaths. These observations describe the recorded events in the study group. The primary endpoint, however, is specifically the percentage of patients with drug-related adverse events up to 140 days after administration. Its numerical result is not reported in the registry record. The general adverse-event counts cannot fill that gap because the record does not say that all events in the other category were considered drug-related.

The registry lists secondary outcomes concerning GPP severity and global assessment, fatigue, pain, and pharmacokinetic exposure. It does not report numerical results for those outcomes in the record summarized for this analysis. Thus, the outcome list shows what the study set out to assess, but it does not establish the observed direction or size of change. No confidence intervals or analysis results are reported in the registry record.

What the record does not establish is also important. With one treatment group, there is no concurrent comparison to estimate how outcomes might differ under another treatment or no treatment. Open-label conduct, small enrollment, and missing details about analysis methods constrain interpretation. The study’s event counts cannot by themselves establish that spesolimab caused or prevented an event, and the absence of recorded serious events in this group does not prove that serious events cannot occur.

General: Clinical interpretation requires attention to both the estimate and its uncertainty, as well as the design that produced it. Here, the primary endpoint estimate and its uncertainty are unavailable in the registry record. The appropriate reading is therefore limited to the design, outcome definitions, and descriptive safety counts that are recorded, without drawing a treatment-effect conclusion.

14. Why This Trial Matters Statistically

This study is statistically notable for the questions it poses and the limits attached to its design. It examines safety and pharmacokinetic objectives in a Phase I setting, while also listing disease severity, fatigue, and pain outcomes. Such a range of outcomes reflects several distinct kinds of measurement: event occurrence, clinical status or change, patient-reported symptoms, and drug concentration. Each type requires an appropriate definition and analysis, and the registry record does not provide the analysis plan or numerical outcome results needed to evaluate those analyses.

The single-group, open-label design is important because it clarifies the role of the data. The study can record what happened among participants who received a single intravenous dose, but it cannot provide a concurrent treatment contrast. That distinction prevents descriptive observations from being mistaken for estimates of comparative treatment effect. It also emphasizes why attribution of adverse events and the exact definition of the primary endpoint matter.

The safety information illustrates the difference between event categories and the primary question. The registry records no serious adverse events among 7 at risk, while other adverse events are recorded for 7 participants. Yet the primary endpoint concerns drug-related events, and its numerical result is not reported. Keeping those quantities conceptually separate is essential: an event count, a serious-event count, and an endpoint percentage answer different questions.

The registry’s limited reporting also makes transparency relevant. The record identifies the outcomes and study population but does not report confidence intervals, missing-data handling, multiplicity procedures, or the statistical analysis plan. These omissions prevent evaluation of precision and analytic choices. The study remains useful as a record of an early-phase investigation and its planned questions, while its posted information does not support a detailed statistical assessment of efficacy or causal safety effects.

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 are specific to this trial and its registry record. The study enrolled 7 participants and had a single treatment group, with no comparator and no masking. These features limit the precision and comparative interpretation of observed outcomes. In particular, the design cannot separate treatment-related changes from the natural course of GPP or other influences, and open-label assessment may affect reporting or measurement.

The primary endpoint is defined as the percentage with drug-related adverse events over a stated period, but its numerical result is not reported in the registry record. Safety counts are available for serious and other adverse events, but the registry does not provide serious-event terms, event timing, or enough detail to equate the “other” category with drug-related events. The primary endpoint therefore cannot be reconstructed from the reported safety counts.

The registry lists secondary outcomes and study objectives, but does not report numerical results for the listed clinical or pharmacokinetic outcomes in the information summarized for this analysis. The methods used to analyze them, confidence intervals, multiplicity procedures, and handling of missing data are not reported in the registry record. The number of observations contributing to each secondary outcome is also not reported.

Other protocol details that could aid interpretation, including the dose amount, detailed eligibility criteria, and the study’s own sample-size justification, are not reported in the registry record. The planning assumptions described for sample-size illustrations are hypothetical and do not represent the design of this single-group study. These gaps mean that the registry record supports a limited descriptive reading, not a complete evaluation of endpoint estimates or statistical methods.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Spesolimab (BI 655130) Single Dose in Generalized Pustular Psoriasis — NCT02978690.
• Registry record last updated 2023-08-21; status last verified 2022-09.
• Results first posted 2023-08-21.
• 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

NCT02978690 is a completed Phase I, multicentre, open-label, single-group study of a single intravenous dose of spesolimab in adults with active generalized pustular psoriasis. The registry records 7 participants enrolled, with a study start date of 2016-12-19 and primary completion date of 2017-09-20.

The primary endpoint is the percentage of patients with drug-related adverse events up to 140 days after administration. Its numerical result is not reported in the registry record. The safety data list 0 serious adverse events among 7 at risk, 7 other adverse events among 7 at risk, and 0 deaths. The registry also lists secondary outcomes for disease severity, global assessment, fatigue, pain, and pharmacokinetics, but does not report numerical results for them in the information.

There is no comparator group. The record does not report a statistical analysis plan, confidence intervals, missing-data methods, or multiplicity procedures. The posted information therefore permits description of the study design and safety counts, but not a comparative treatment-effect estimate or a numerical interpretation of the primary endpoint.