This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Test Long-term Treatment With Spesolimab in Patients With Fistulising Crohn's Disease Who Took Part in Previous Trials (NCT04362254), a na phase 2 study. The primary outcome is Exposure Adjusted Rate of Patients Reporting a Treatment Emergent Adverse Event (TEAE) During Maintenance Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04362254 |
| Phase | Phase 2 |
| Condition | Crohn Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
People with perianal fistulising Crohn's disease who had completed treatment in previous spesolimab trials. The registry record lists an enrollment of 12. The safety population is defined as patients who received at least one dose of trial drug during the maintenance period.
Intervention
Long-term treatment with spesolimab. During maintenance, 300 mg was given by subcutaneous injection at Week 0 and then every 4 weeks for a total duration of 89 weeks. The record also describes a single 1200 mg intravenous infusion for confirmed fistula relapse, followed by an intensifi…; the remainder of that regimen is not reported in the registry record.
Comparator
There was no randomized comparator group. The trial is described as single-group, with allocation listed as not applicable and masking listed as none. Consequently, its posted results do not provide a like-for-like comparison with another treatment or a control group.
Primary question
The primary outcome asks for the exposure-adjusted rate of patients reporting a treatment-emergent adverse event during maintenance treatment. The stated unit is patients with a treatment-emergent adverse event per 100 patient-years. The trial's summary also identifies long-term safety and efficacy as objectives, but the primary numerical rate is not reported in the registry record.
3. Trial Design
This was a Phase 2, open-label, long-term safety trial of spesolimab in patients with Crohn's disease who had completed previous spesolimab trials. The brief description focuses on perianal fistulising Crohn's disease. A single-group design means that the trial followed patients receiving spesolimab rather than assigning participants to separate treatment and control groups. Allocation is listed as not applicable, and masking as none.
The registry record lists enrollment of 12 and a terminated status. It gives a study start date of 2020-05-15 and a primary completion date of 2022-05-14. The reason for termination is not reported in the registry record, so the status alone does not establish why the study ended or what effect termination had on follow-up.
During maintenance treatment, the described regimen was 300 mg spesolimab by subcutaneous injection at Week 0 and then every 4 weeks for a total duration of 89 weeks. The record also describes a single intravenous infusion of 1200 mg for a confirmed fistula relapse, followed by an intensifi…; further details of that regimen are not reported in the registry record.
The primary outcome covers the period from the first dose in this trial through the last dose plus 16 weeks, described as approximately 104 weeks. Because the study is open label and has no control group, its design can describe events observed during treatment and follow-up, but it does not offer a randomized estimate of how outcomes compare with another treatment. The protocol's rationale for this design and any sample-size justification are not reported in the registry record.
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
| Stage | Spesolimab |
|---|---|
| STARTED | 12 |
| COMPLETED | 0 |
| NOT COMPLETED | 12 |
Reasons for not completing this period:
| Reason | Spesolimab |
|---|---|
| Adverse Event | 1 |
| Protocol Violation | 1 |
| Due to early termination of the trial | 10 |
Analysis population for the primary outcome, as defined in the registry: The safety set (SAF) included all patients who received at least one dose of trial drug in the overall maintenance period.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: The safety set (SAF) included all patients who received at least one dose of trial drug in the overall maintenance period.
| Characteristic | Unit | Spesolimab |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 37.1 (SD 10.2) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 12 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 10 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Exposure Adjusted Rate of Patients Reporting a Treatment Emergent Adverse Event (TEAE) During Maintenance Treatment, measured over First dose of Spesolimab in this trial through to the last dose of spesolimab + 16 weeks, approximately 104 weeks..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Patients with TEAE per 100 patient years |
| Endpoint classification | Event-Rate Endpoint |
The primary endpoint is the exposure-adjusted rate of patients reporting a treatment-emergent adverse event during maintenance treatment. A treatment-emergent adverse event is an event recorded as arising during the trial's treatment period; the endpoint description focuses on patients reporting such an event. Its unit is patients with a treatment-emergent adverse event per 100 patient-years.
The registry describes the rate as 100 multiplied by the number of patients with a treatment-emergent adverse event, divided by the total event-specific time at risk. For patients who experienced an event, time at risk runs from the study drug start date through the event's onset date, with one day added, and is expressed in subject-years using 365.25 days per year. For patients without an event, it runs from the study drug start date through the end of their time at risk, again with one day added.
In general, exposure adjustment accounts for the amount of time people are observed and at risk, rather than treating follow-up time as identical for everyone. This can make a rate useful when exposure durations vary. It is not the same as the proportion of patients with an event, and it does not by itself describe how severe, persistent, or clinically consequential an event was. The registry record does not report the numerical primary endpoint rate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome is defined, but its numerical result is not reported in the registry record. The record therefore does not establish the observed exposure-adjusted rate of patients reporting a treatment-emergent adverse event during maintenance treatment. Without that rate, its precision, or a reported analysis, the primary endpoint cannot be quantitatively interpreted from the registry information.
The adverse-event information that is listed has a different form from the primary endpoint. For the Spesolimab group, the registry reports 12 patients at risk for serious adverse events and 1 affected. It reports 12 at risk for other adverse events and 11 affected. The deaths figure is 0. These are the posted patient counts for those categories; they should not be treated as the exposure-adjusted primary rate. The record also lists Fistula as the top serious term at 8.3%.
In general, an exposure-adjusted rate incorporates time at risk, while a patient count indicates how many patients were recorded as affected in a category. These measures answer related but different questions. The listed counts do not disclose how long each patient was observed, when each event occurred, or the full distribution of event types and severity. They should not be converted into a rate without the relevant exposure-time data.
The study's single-group, open-label design also limits comparative interpretation. There is no randomized control group against which to distinguish events associated with treatment from events that might occur because of the underlying condition, other circumstances, or time under observation. The population had already completed previous spesolimab trials, so these findings concern people with that treatment history and should not automatically be generalized to all people with Crohn's disease.
The registry lists the trial as terminated, but the reason is not reported in the registry record. The available information does not establish whether termination changed the planned follow-up or analysis. Nor does it report a numerical primary estimate or confidence interval. As a result, interpretation should remain descriptive: the record provides an endpoint definition and some adverse-event counts, but not a reported primary rate with which to assess its magnitude or precision.
9. Statistical Methods Explained
The endpoint uses an exposure-adjusted rate, a statistical summary that incorporates both the number of patients with an event and the time they contribute while at risk. The registry's stated unit, patients with a treatment-emergent adverse event per 100 patient-years, expresses the event count in relation to accumulated observation time. The registry record specifies the rate calculation and time-at-risk rules, but does not report the resulting primary rate.
Why adjust for exposure time?
In general, patients may be observed for different lengths of time. A simple count of patients with an event does not account for that variation. An exposure-adjusted rate uses person-time as its denominator, so it describes event occurrence relative to time under observation. This can be useful for summarizing safety experience when follow-up differs. It does not make groups comparable by itself, and it does not remove differences in patient characteristics, treatment history, or circumstances of observation.
The registry defines time at risk separately according to whether a patient experienced a treatment-emergent adverse event. For a patient with an event, the interval ends at the event's onset; for a patient without an event, it ends at the recorded end of time at risk. Each duration includes one day, and conversion to subject-years uses 365.25 days. The rate is then scaled to the stated unit of 100 patient-years. No additional rate can be recovered from the reported patient counts alone because the total event-specific time at risk and the primary estimate are not reported in the registry record.
What does the rate describe?
In general, a rate describes the frequency of events relative to time, rather than the probability that an individual patient will experience an event over a fixed period. A rate is also not a measure of severity. The endpoint wording refers to patients reporting an event, while the registry's calculation uses the number of patients with an event and event-specific time at risk. It should therefore be read according to that stated definition rather than as a complete account of event burden or clinical impact.
A confidence interval, in general, describes statistical uncertainty around an estimated quantity under the assumptions of the analysis. The registry record does not report a primary rate estimate or its confidence interval. Accordingly, the precision of the primary endpoint cannot be assessed from the registry information. The record also does not report a statistical analysis plan, an inferential test for this endpoint, or interim analyses.
What do the design and analysis population imply?
This is a single-group, open-label study. In general, a single-group rate can describe observed experience in the treated group, but without a concurrent comparator it cannot isolate a treatment effect. Open-label conduct means masking is listed as none; the registry record does not describe any procedures that would mitigate awareness of treatment assignment. These design features matter when interpreting reports of events, particularly where event recognition or reporting may involve judgment.
The safety set is defined as all patients who received at least one dose of trial drug in the overall maintenance period. This population definition identifies who is intended to contribute to the safety assessment. The registry lists 12 patients at risk in each of the serious and other adverse-event categories, but the primary endpoint's analyzed population and its numerical result are not reported separately. The enrollment figure should not be assumed to establish the number included in every analysis.
How should planning illustrations be read?
In general, a sample-size calculation estimates the amount of information a future study might need under specified assumptions. The planning illustrations associated with this trial use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. They are planning illustrations, not observed power and not the trial's reported design justification. Since the trial is single-group and the registry record does not report a numerical primary result, those illustrations should not be mistaken for an analysis of this trial's observed primary endpoint. The protocol's own sample-size rationale is not reported in the registry record.
The record identifies secondary outcomes for perianal fistula remission and perianal fistula response. The definition of those outcomes, their results, and their analysis details are not reported in the registry record. The record lists three outcome measures, but the available information does not give a complete account of outcome-level methods or results. No adjusted or recalculated primary estimate is reported, and there is no basis for describing statistical significance or the precision of an effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies the primary outcome as an exposure-adjusted rate of patients reporting a treatment-emergent adverse event. It also names secondary outcomes for the proportion of patients with perianal fistula remission and the proportion with perianal fistula response. The record lists three outcome measures overall, but does not report a multiplicity adjustment or a statistical plan for handling multiple outcomes. In general, when several outcomes are examined, multiplicity procedures may be used to control the chance of false-positive findings across tests. Whether any such procedure was planned or used is not reported in the registry record.
Missing-data methods are not reported in the registry record. The information does not specify how incomplete follow-up, missing event information, or unavailable secondary-outcome assessments were handled. It also does not report whether any sensitivity analyses assessed the effect of missing data. These omissions limit the ability to evaluate how missing observations may relate to the posted findings.
The safety set is defined as all patients who received at least one dose of trial drug during the overall maintenance period. That definition clarifies the intended safety population, but does not by itself show the number contributing to each analysis or the handling of patients with incomplete exposure information. The adverse-event categories list 12 at risk for serious events and 12 at risk for other events. The primary endpoint's numerical analysis result is not reported in the registry record.
The registry record lists no analyses. It does not report a statistical analysis plan, interim analyses, or the handling of multiplicity and missing data. Those methods should not be inferred from the endpoint definition or from the descriptive adverse-event counts.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Spesolimab | 1 | 12 | 8.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Spesolimab | 0 of 12 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Spesolimab | 11 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Spesolimab |
|---|---|---|
| Fistula | Musculoskeletal and connective tissue disorders | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Spesolimab |
|---|---|---|
| COVID-19 | Infections and infestations | 6 of 12 |
| Injection site erythema | General disorders | 3 of 12 |
| Nasopharyngitis | Infections and infestations | 2 of 12 |
| Fistula | Musculoskeletal and connective tissue disorders | 2 of 12 |
| Pruritus | Skin and subcutaneous tissue disorders | 2 of 12 |
| Abdominal pain | Gastrointestinal disorders | 1 of 12 |
| Anal polyp | Gastrointestinal disorders | 1 of 12 |
| Rectal stenosis | Gastrointestinal disorders | 1 of 12 |
| Inflammation | General disorders | 1 of 12 |
| Injection site reaction | General disorders | 1 of 12 |
Serious events with the highest arm-level rate: fistula (8.3%).
The registry lists 12 patients at risk for serious adverse events, with 1 affected. In the other adverse-event category, it lists 12 at risk and 11 affected. The deaths figure is 0. These are patient counts in the posted safety information; they are not the exposure-adjusted primary endpoint result, and the counts should not be added together to infer a total number of affected patients.
Fistula is listed as the top serious adverse-event term at 8.3%. This term-level figure should be read as reported, without assuming that it gives the number of events or identifies how many patients experienced the term. The registry information does not provide the event narratives, timing, duration, or full severity detail needed to characterize each report.
In general, serious adverse-event status is a classification of an event, while the endpoint rate concerns event reporting relative to time at risk. The two summaries are not interchangeable. The registry does not report total event-specific exposure time or the primary rate, so the serious and other patient counts cannot be used to reconstruct that rate. Nor does the single-group design establish how these events compare with another treatment or with the background course of the condition.
12. What the Result Does, and Does Not, Mean
The posted registry information describes a long-term, open-label, single-group study of spesolimab among patients with perianal fistulising Crohn's disease who had completed previous spesolimab trials. It defines the primary safety endpoint and gives patient counts for serious and other adverse-event categories. It also reports 0 deaths and lists Fistula as the top serious term at 8.3%.
The registry record does not report the numerical result for the primary exposure-adjusted rate. It therefore does not show the rate's magnitude or precision. The patient counts cannot substitute for that rate because the rate incorporates time at risk, and the total event-specific exposure time is not reported. The available information also does not provide a full account of the type, timing, duration, or consequences of all events.
In general, observing events among people who receive a treatment is not enough to determine whether the treatment caused those events. A single-group study lacks a concurrent randomized comparator, and open-label conduct does not conceal treatment from participants or investigators. The trial can describe safety experience in its observed population, but it cannot by itself establish a comparative treatment effect.
The trial's stated objectives also include long-term efficacy, and the registry names outcomes for perianal fistula remission and response. Their numerical results and detailed analysis methods are not reported in the registry record. No conclusion about those outcomes can be drawn from their titles alone.
The study is listed as terminated, but the reason for termination is not reported in the registry record. The available information does not establish the implications of that status for follow-up or outcome reporting. Overall, the record supports a limited descriptive reading of the listed safety counts and study design, not a conclusion about comparative safety or efficacy.
13. Why This Trial Matters Statistically
This trial illustrates why an adverse-event endpoint may be expressed as a rate rather than only as a patient count. The primary outcome relates patients reporting treatment-emergent adverse events to event-specific time at risk, producing a measure per 100 patient-years. In general, this approach recognizes that people may contribute different amounts of follow-up. It also makes clear why event counts alone cannot reproduce an exposure-adjusted result.
The study also shows the interpretive limits of a single-group, open-label design. Such a study can document events in a defined treatment setting and population, but it lacks a randomized concurrent group for comparative interpretation. Treatment history is also central: participants had completed previous spesolimab trials, so this is a selected population rather than an unselected group of people with Crohn's disease.
For biostatistical reading, the distinction between an endpoint definition and its result is important. The registry describes how the primary rate is intended to be calculated, yet the numerical rate and its precision are not reported. A method alone does not tell readers what was observed. Similarly, descriptive adverse-event counts should not be treated as an estimate of comparative risk or as a substitute for person-time information.
The record lists secondary remission and response outcomes but does not report their results or the approach to multiplicity. Missing-data handling and the trial's own sample-size rationale are also not reported in the registry record. These gaps reinforce the need to separate what a registry entry specifies from what it actually reports as an analysis. The study is statistically informative as an example of an exposure-adjusted safety question, while its available numerical reporting constrains the conclusions that can be drawn.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry lists enrollment of 12, and the safety categories each list 12 patients at risk. The amount of information available for assessing uncommon or variable events is therefore limited. The primary numerical rate and a measure of its precision are not reported in the registry record, preventing assessment of how stable or uncertain that estimate would be.
The trial has no randomized comparator and is open label. Its results cannot provide a like-for-like comparison with another treatment, and the design does not separate treatment-associated events from other possible causes. The participants had completed previous spesolimab trials, which narrows the population to people with that treatment history. Generalization beyond this group requires caution.
The study is listed as terminated, but the reason is not reported in the registry record. The information does not establish whether termination affected the intended duration of observation, completeness of follow-up, or planned analyses. The primary outcome timeframe is described as extending from the first dose through the last dose plus 16 weeks, approximately 104 weeks, but the record does not provide patient-level follow-up or total event-specific time at risk.
The record does not report missing-data methods, a statistical analysis plan, multiplicity procedures, interim analyses, or the protocol's sample-size justification. It names secondary remission and response outcomes but does not report their numerical results or detailed definitions. These omissions limit appraisal of outcome ascertainment and analysis choices. The adverse-event figures are descriptive counts; they do not reveal event timing or duration, and they cannot be used to reconstruct the unreported exposure-adjusted primary rate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Test Long-term Treatment With Spesolimab in Patients With Fistulising Crohn's Disease Who Took Part in Previous Trials — NCT04362254.
- Registry record last updated 2025-02-24; status last verified 2025-02.
- Results first posted 2024-11-05.
- 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.
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18. Record Summary
This Phase 2 study evaluated long-term spesolimab treatment in patients with perianal fistulising Crohn's disease who had completed previous spesolimab trials. It was open label and single group, with enrollment listed as 12. The registry lists the study as terminated.
The primary outcome was the exposure-adjusted rate of patients reporting a treatment-emergent adverse event during maintenance treatment, expressed per 100 patient-years. The numerical primary result is not reported in the registry record. Safety information lists 1 affected among 12 at risk for serious adverse events, 11 affected among 12 at risk for other adverse events, and 0 deaths. Fistula is listed as the top serious term at 8.3%.
The registry names secondary outcomes for perianal fistula remission and response. Their results, the reason for termination, and details of missing-data and multiplicity methods are not reported in the registry record. The single-group design supports descriptive interpretation of the listed safety information, not a randomized comparison.