A Study Investigating Long-term Treatment With Spesolimab in People With a Skin Disease Called Hidradenitis Suppurativa Who Completed a Previous Clinical Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Investigating Long-term Treatment With Spesolimab in People With a Skin Disease Called Hidradenitis Suppurativa Who Completed a Previous Clinical Trial (NCT04876391), a na phase 2 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, long-term extension trial of spesolimab in adults with hidradenitis suppurativa. Participants had taken part in a previous clinical study and completed treatment before joining. The registry record describes the extension as completed, with enrollment of 45. It records a start date of 2021-08-24 and a primary completion date of 2024-04-26.

The trial had a single-group model and no allocation. Masking was absent. Although the registry lists two groups according to prior treatment—Prior Placebo (PP) and Prior Spesolimab (PS)—these are histories from the parent trial, not randomized extension assignments. The registry explicitly cautions that the groups are not a like-for-like control comparison. Consequently, differences between their recorded outcomes cannot be interpreted as randomized treatment effects of the extension.

The brief summary describes participants receiving subcutaneous spesolimab injections every two weeks for two years and attending visits to assess disease severity and collect health information. The study duration is described as about 2 years and 4 months. The listed intervention names include spesolimab 1200 mg, spesolimab 600 mg, and matching placebo preparations. The registry record does not give a complete account of how extension doses were assigned or changed over time.

The primary endpoint concerned participants with treatment-emergent adverse events from treatment initiation through the end of the maintenance period, including a residual effect period after the last study treatment. The registry lists secondary measures of abscess and inflammatory nodule counts, draining fistula counts, clinical response, severity scores, flares, and pain through Week 12. The registry record does not report analysis results for these secondary measures.

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: Safety Analysis Set (SAF): This participant set included all participants who were enrolled and received at least one dose of study drug.

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: Safety Analysis Set (SAF): The safety analysis set includes all participants who received at least one dose of the trial drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs), measured over From drug administration until the end of maintenance treatment period (120 weeks). This period includes the Residual effect period (REP) (i.e., 16 weeks after the last study treatment)..

The primary endpoint was the number of participants with treatment-emergent adverse events (TEAEs). This is a participant-count outcome: it records whether participants experienced events meeting the endpoint definition, rather than measuring the number of events per participant or the duration of an event.

The registry defines TEAEs as adverse events occurring from the start of treatment in the extension through the end of its residual effect period. Events that began during the on-treatment period of the parent trial and continued into the extension were also considered treatment-emergent. The specified period runs from drug administration through the end of maintenance treatment, described as 120 weeks, and includes a 16-week residual effect period after the last study treatment.

Safety endpoints of this kind are used to describe the adverse-event experience during and after treatment exposure. They are particularly relevant in a long-term extension, where participants are followed during continued treatment. A participant count does not, by itself, describe event severity, duration, recurrence, or causal attribution. Those require additional information and definitions.

The registry identifies the Safety Analysis Set as participants who were enrolled and received at least one dose of study drug. It does not report an overall numerical result for the primary TEAE endpoint in the record. The listed serious and other adverse-event counts provide safety information, but should not be assumed to be a complete report of the primary endpoint without a direct endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome is a count of participants who experienced at least one event meeting the TEAE definition. This differs from counting every event: a person with repeated events may still contribute as one participant to a participant-count endpoint. The registry identifies the analysis set as enrolled participants who received at least one dose of study drug. It does not report the overall primary-endpoint count in the record.

For a binary outcome, each participant is classified according to whether the defined event occurred during the stated observation period. Such outcomes are often presented as counts and proportions. A proportion can aid interpretation by relating the count to the number assessed, but it does not explain how severe or persistent the events were. No confidence interval or other measure of uncertainty for the primary TEAE outcome is reported in the registry record.

Why does the outcome period matter?

The TEAE definition covers the period beginning with treatment in the extension and continuing through the residual effect period after the last study treatment. It also includes certain adverse events that began during the parent trial and remained ongoing in the extension. This definition is important when interpreting the endpoint: it is not limited to newly starting events after entry into the extension. The stated period is the maintenance treatment period of 120 weeks, including a 16-week residual effect period.

In general, outcome definitions and observation windows determine which events can count. Different windows or rules for ongoing events can produce different endpoint counts even when the underlying participants are the same. Readers should therefore use the registry definition rather than assume that “treatment-emergent” has an identical meaning across trials.

What can comparisons between PP and PS establish?

The registry lists PP and PS groups based on treatment received in the earlier trial. It also states that the extension was not a randomized comparison and that the groups are not like-for-like controls. In general, group comparisons are more vulnerable to confounding when group membership is not assigned randomly for the comparison being made. Prior trial treatment, participant characteristics, exposure history, and selection into an extension may differ between groups. The record does not provide an adjusted analysis to address such differences.

Because the extension had a single-group model and no allocation, the group counts are appropriately treated as descriptive. A numerical difference between them should not be presented as an estimated causal effect. The registry record lists no analyses for the posted outcome set, and no inferential comparison is reported.

Why do confidence intervals matter?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified analysis. It helps readers distinguish a relatively precise estimate from one that is compatible with a wide range of underlying values. A count alone does not convey that uncertainty, and a confidence interval cannot remedy design limitations such as the absence of a randomized comparator. The registry record does not report confidence intervals for the safety counts.

For event outcomes, precision depends in part on the amount of information available and on how frequently the event occurs. Rare events can remain uncertain even in a study with prolonged follow-up. This is a general statistical point, not a claim about the likelihood of any particular event in this trial.

How should missing analyses be understood?

The registry lists nine secondary outcome measures but does not report their numerical results in this record. It also records zero analyses. This absence means the registry record does not support interpretation of effect estimates, uncertainty intervals, or statistical tests for those outcomes. It does not establish why results are absent or whether analyses were performed elsewhere.

In general, outcome results require more than a measure name: they need the analyzed population, the number assessed at each time point, the estimate, and appropriate uncertainty information. Missing result reporting leaves those elements unavailable for evaluation. Likewise, a listed outcome should not be treated as a positive or negative finding merely because it appears in the registry.

No statistical analysis plan, model specification, interim analysis plan, or sample-size justification is reported in the registry record. These details should not be inferred from the study design or from the fact that it is a Phase 2 extension. Any planning illustration associated with an observed effect would be a hypothetical design calculation, not observed power; the record does not provide an observed treatment-effect estimate for these outcomes.

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("Prior Placebo (PP)", "Prior Spesolimab (PS)")
n      <- c(15, 30)
events <- c(15, 28)
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  Prior Placebo (PP)  15  15  100.0  78.2  100.0  79.6  100.0  79.4  99.8
ARM  Prior Spesolimab (PS)  30  28  93.3  77.9  99.2  78.7  98.2  78.6  98.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists nine secondary outcomes, covering lesion counts, clinical response, disease severity, flares, and pain through Week 12. It does not report numerical results for them in the registry record, and it records zero analyses. The record does not report a multiplicity strategy, such as a prespecified ordering of tests or an adjustment for evaluating several outcomes. It would therefore be inappropriate to infer which outcomes were considered confirmatory or to treat any unreported outcome as evidence of benefit or lack of benefit.

The registry record does not report a missing-data method, the number of participants assessed at each secondary endpoint time point, or a description of missing observations. It also does not give a statistical analysis plan specifying how incomplete follow-up or unavailable measurements were handled. In general, missing observations can affect estimates if the probability of missingness is related to participant status or outcomes; the direction and extent of any effect depend on the data and assumptions. No such assessment can be made from the available record.

The primary safety analysis set includes enrolled participants who received at least one dose of study drug. This defines who is included in the stated safety population, but does not establish the analysis population used for each secondary outcome. The record does not report those populations or outcome-specific denominators.

There is no randomized comparison in the extension, and the prior-treatment groups are not like-for-like controls. Together with the absence of reported analyses and missing-data details, this limits both comparative interpretation and assessment of precision. Reasons for the absent results and details of any analyses are not reported in the registry 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: acute hepatitis c (6.7%), latent tuberculosis (6.7%), vulval abscess (6.7%), hidradenitis (6.7%), pancreatitis (3.3%).

The registry lists serious adverse-event counts of 4 among 15 participants in Prior Placebo (PP) and 6 among 30 in Prior Spesolimab (PS). For other adverse events, it lists 15 among 15 in PP and 27 among 30 in PS. The recorded death count is 0 in each group. These entries should be read as descriptive safety information, not as a randomized comparison of treatment groups.

The listed serious-event terms include Acute hepatitis C, Latent tuberculosis, Vulval abscess, and Hidradenitis at 6.7% each, and Pancreatitis and Abdominal abscess at 3.3% each. The registry record does not supply further detail about severity, duration, recurrence, event-level overlap, or causal attribution. The listed terms therefore do not establish that spesolimab caused an event.

The primary endpoint is TEAEs, which has a defined observation period and includes some events continuing from the parent trial. The registry record does not report an overall numerical result for that endpoint. The serious and other adverse-event counts should not be treated as a complete substitute for it. In general, safety counts describe what was recorded in the stated population and follow-up; without a randomized comparator, they do not establish what would have happened under another treatment or no treatment.

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

The registry record describes a completed, open-label extension focused primarily on safety during long-term spesolimab treatment and follow-up. It identifies a participant-count safety endpoint and provides some serious and other adverse-event counts by prior-trial group. It also lists serious adverse-event terms and records no deaths in either group. These findings are descriptive of the reported participants and should be read within the stated design and outcome definitions.

The record does not report the overall numerical result for the primary TEAE endpoint. It also does not report numerical results for the listed secondary disease activity outcomes. Consequently, it does not establish the magnitude or precision of any change in disease activity, clinical response, pain, or flare occurrence. Outcome titles describe what was planned or collected, not what the results were.

The two groups are defined by prior treatment in the parent trial, not by randomized assignment in this extension. The registry explicitly warns that they are not like-for-like control groups. Their counts therefore cannot be used to estimate a causal contrast between spesolimab and placebo in the extension. The open-label design also means outcomes were recorded without masking, a feature relevant to interpretation of assessments and reporting.

More generally, a safety extension can provide descriptive information about events observed during continued exposure, but it does not by itself determine how outcomes would compare under an alternative treatment. A count does not establish causation, and a lack of a reported event in a group does not establish that the event cannot occur. The registry record does not report confidence intervals or a formal analysis of uncertainty for the counts.

The record also does not report the analysis plan, handling of missing data, or reasons numerical outcome results are absent. These omissions limit independent assessment of the intended analyses and the completeness of outcome reporting. The appropriate conclusion is therefore narrow: the registry records certain safety counts in an open-label extension population, while leaving the primary endpoint result and secondary outcome results unreported in the registry record.

14. Why This Trial Matters Statistically

Long-term extension trials address a question that a shorter parent study may not fully describe: what safety events are recorded during continued treatment and subsequent follow-up. This trial followed adults with hidradenitis suppurativa who had taken part in an earlier study. Its stated primary outcome was a participant count of treatment-emergent adverse events, with a definition that includes events continuing from the parent trial and a residual effect period after the last extension treatment.

Statistically, the design matters as much as the outcome. An open-label, single-group extension can describe observed events, but it does not create a randomized comparator for estimating what would have happened under another treatment. Prior-treatment categories can help organize descriptive reporting, yet the registry cautions that PP and PS are not like-for-like controls. This is a useful reminder that group labels do not by themselves establish comparability.

The record also illustrates why registry outcome names and numerical results must be distinguished. It lists nine secondary outcomes through Week 12, but does not report their numerical results or analyses. Without estimates, denominators, and uncertainty information, readers cannot assess the direction or precision of those outcomes. Similarly, the registry defines a primary safety endpoint but does not report its overall count.

These features make the record informative about design, endpoint definitions, and selected safety counts, while also setting clear limits on inference. Careful statistical reading separates descriptive observations from causal effects, and separates outcomes listed in a registry from results actually reported. That distinction is important when evaluating long-term safety evidence and the completeness of clinical trial reporting.

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.

This trial has no randomized comparator within the extension. The registry identifies PP and PS according to prior-trial treatment and explicitly states that the groups are not like-for-like controls. Therefore, comparisons between their safety counts cannot establish a treatment effect. The open-label design also means treatment was not masked.

The registry record does not report the overall numerical result for the primary TEAE endpoint, despite defining the endpoint and its observation period. It also does not report numerical results or analyses for the nine secondary outcomes. As a result, the direction and precision of disease activity findings cannot be assessed from the registry record.

Further interpretive details are not reported in the registry record, including confidence intervals for the listed safety counts, outcome-specific analysis populations and denominators, handling of missing data, a statistical analysis plan, and reasons numerical results are absent. The serious adverse-event terms and counts do not provide information about event-level overlap, duration, or causal attribution in the record.

The extension enrolled adults with hidradenitis suppurativa who had taken part in a previous trial and completed treatment. Its findings therefore describe this selected extension population, rather than all people with the condition. The registry record does not provide enough information to determine how selection into the extension affected the observed safety experience. These limitations constrain generalization and comparative inference without changing the descriptive details that are reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Investigating Long-term Treatment With Spesolimab in People With a Skin Disease Called Hidradenitis Suppurativa Who Completed a Previous Clinical Trial — NCT04876391.
• Registry record last updated 2025-11-14; status last verified 2025-11.
• Results first posted 2025-06-08.
• 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

NCT04876391 is a completed Phase 2, open-label, long-term extension trial of spesolimab in adults with hidradenitis suppurativa who participated in an earlier clinical study. The registry reports enrollment of 45, a start date of 2021-08-24, and a primary completion date of 2024-04-26. The design is listed as single-group with no allocation and no masking.

The primary outcome was the number of participants with treatment-emergent adverse events during treatment and the residual effect period. The registry lists nine secondary disease activity and symptom outcomes through Week 12, but reports no analyses or numerical results for those outcomes. The overall primary endpoint count is not reported in the registry record.

Safety entries include serious and other adverse-event counts for PP and PS, groups defined by prior-trial treatment, as well as selected serious-event terms. The registry cautions that these are not like-for-like control groups. The counts are descriptive and do not provide a randomized treatment comparison.