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 This Study Tests How BI 655130 Works in Patients With Active Ulcerative Colitis. The Study Also Tests How Well BI 655130 is Tolerated and Whether it Helps the Patients (NCT03100864), a na phase 2 study. The primary outcome is The Total Number of Deregulated Genes Comparing Baseline to Post Treatment, Analysed by Gene Expression of Mucosal Biopsies Via RNA Sequencing, Per Time Point up to Week 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03100864 |
| Phase | Phase 2 |
| Condition | Colitis, Ulcerative |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
Patients with active ulcerative colitis. The registry lists an enrollment of 8 and describes the primary endpoint population as a completers analysis set.
Intervention
Spesolimab, identified in the trial title as BI 655130. The treatment group is listed as receiving 1200 mg intravenously.
Comparator
There was no separate comparator group: the design is listed as single group, with allocation recorded as NA and masking as none.
Primary question
How many genes were classified as deregulated when mucosal biopsy gene expression after treatment was compared with baseline at each stated time point?
The trial’s primary objective was to understand the mechanism of action of BI 655130 in ulcerative colitis. Its primary outcome therefore concerns molecular changes in mucosal biopsies, rather than a direct comparison of treatment with a control. The registry also lists secondary outcomes covering changes in C-reactive protein, faecal calprotectin and faecal lactoferrin, clinical remission at Week 12, and drug-related adverse events. Numerical results for those outcomes are not reported in the registry record.
This design can describe observations during treatment in the enrolled group, but it does not provide a randomized between-group estimate. Without a control group, changes from baseline cannot by themselves distinguish treatment-associated change from other explanations, such as natural variation over time. The record’s clinical question is exploratory and includes both biological and clinical measures; it does not report a comparative test of spesolimab against another treatment or against no treatment.
3. Trial Design
This was a phase 2 exploratory trial of spesolimab, also called BI 655130 in the trial title, in patients with active ulcerative colitis. The registry describes the study as single group, records allocation as NA, and lists masking as none. The intervention group is titled Spesolimab 1200 mg Intravenous (i.v.). Enrollment was 8, and the status is completed.
The study began on 2017-05-22, and its primary completion date was 2019-08-05. The official title describes 12 weeks of treatment. The primary objective was to understand mechanism of action; secondary objectives were to explore clinical effect, safety and tolerability, including immunogenicity. These stated objectives indicate an exploratory scope rather than a randomized treatment comparison.
The primary endpoint concerns the total number of deregulated genes comparing baseline with post-treatment mucosal biopsy gene expression, assessed by RNA sequencing at each time point. The listed measurements were at baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12). Secondary outcomes include percentage changes in three biomarkers from baseline to Week 12, clinical remission at Week 12 using the stated Mayo Score definition, and the number of patients with drug-related adverse events.
Because there was no separate control group and masking was none, the design does not support a blinded, randomized comparison. The registry record does not report a comparator intervention or a separate control arm. Numerical results for the primary and secondary outcomes 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 1200 mg Intravenous (i.v.) |
|---|---|
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Completers analysis set: completed the trial medication through to end of trial visit, had a baseline and at least 1 post baseline measurement for any clinical efficacy or biomarker endpoint without any Important protocol deviation flagged for exclusion or rescue use on or after Visit 1b but prior to administration of the first dose of spesolimab.
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): patients who received at least 1 dose of study drug, who had a baseline and at least 1 post baseline measurement for any clinical efficacy or biomarker endpoint without any Important protocol deviation flagged for exclusion or rescue use on or after Visit 1b but prior to administration of the first dose of spesolimab.
| Characteristic | Unit | Spesolimab 1200 mg Intravenous (i.v.) |
|---|---|---|
| Participants analysed | 8 | |
| Age, Continuous | years | 43.1 (SD 19.1) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 5 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 8 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| 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 | 8 |
| 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 The Total Number of Deregulated Genes Comparing Baseline to Post Treatment, Analysed by Gene Expression of Mucosal Biopsies Via RNA Sequencing, Per Time Point up to Week 12, measured over Measurements done at baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12)..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | deregulated genes |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint counts genes classified as deregulated when mucosal biopsy gene expression after treatment is compared with baseline. The assessment uses RNA sequencing and is expressed as a number of genes for each stated time point, rather than as a clinical score or a change in a single biomarker. The time points listed are baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12).
The registry says that 60,675 genes were evaluated and that 40,586 genes were included in differential expression analyses. It describes use of the DESeq2 method based on raw read counts. A gene was considered deregulated when its FDR-adjusted p-value was < 0.01 and its fold change was at most -1.3 or at least 1.3. These criteria combine evidence against a null hypothesis with a threshold for the magnitude and direction of gene-expression change.
The endpoint fits the stated objective of exploring mechanism of action: it quantifies the breadth of gene-expression changes rather than establishing a clinical benefit. General: a gene-count endpoint can summarize many molecular signals, but its meaning depends on the statistical criteria and analysis population. It does not by itself show whether a change improves symptoms or health. The observed gene counts at the time points are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a single-group exploratory study with enrollment of 8 and no randomized comparator. Its primary endpoint is a molecular count: the number of genes meeting the stated criteria for deregulation in mucosal biopsy gene-expression analyses. The record explains how genes were selected for that count, but the observed counts at the listed time points are not reported in the registry record. Consequently, the record does not support a numerical description of the magnitude or pattern of gene-expression changes.
The primary objective was to understand mechanism of action. In that context, the endpoint is intended to characterize biological change over time. It should not be read as a direct measure of clinical remission, symptom improvement, or comparative effectiveness. The registry separately lists Week 12 clinical remission and changes in C-reactive protein, faecal calprotectin and faecal lactoferrin as secondary outcomes. Their numerical results are not reported in the registry record, so no conclusions about those outcomes can be drawn from the listed endpoint definitions alone.
General: a confidence interval describes the range of estimates compatible with data and a specified statistical model, and communicates precision as well as the estimate itself. No confidence interval or gene-count estimate is reported in the registry record. With no estimate or uncertainty interval, the precision of any treatment-associated change cannot be assessed from this record. The design also lacks a separate comparator group. Thus, even if within-group changes were reported, a before-and-after pattern alone would not isolate the effect of treatment from changes that could occur over time for other reasons.
The registry describes DESeq2 analysis of raw read counts and defines deregulation using an FDR-adjusted p-value threshold and fold-change thresholds. Those criteria are important to interpretation because they determine which genes contribute to the endpoint. They do not substitute for reported results: the record does not state how many genes met the criteria at each time point, nor does it report the direction-specific counts or estimates for individual genes.
The safety record lists serious adverse events affecting 2 participants in the spesolimab group, and lists Colitis and Diverticulitis among the top serious terms, each at 12.5%. These are descriptive safety entries from a small single-group study; they do not establish comparative risk. Deaths are listed as 0. The record also lists other adverse events affecting 8 participants. Those counts should be read as reported observations, not as proof of causation or as a comparison with another treatment.
The registry includes planning assumptions for hypothetical sample-size illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are not the actual single-group design and do not constitute observed power. No sponsor sample-size justification or reported statistical analysis plan is described in the registry record. Any sample-size illustration is a planning calculation, not evidence about the trial’s observed precision or results.
9. Statistical Methods Explained
The primary outcome is based on differential gene-expression analysis of mucosal biopsy RNA sequencing. The registry states that the analysis used raw read counts and the DESeq2 method, described as one of the standard methods for RNA sequencing. It reports 60,675 genes evaluated and 40,586 genes included in the differential expression analyses. Numerical outcome counts are not reported in the registry record.
What does the gene-count endpoint represent?
For each post-baseline time point, the endpoint counts genes meeting the registry’s criteria when compared with baseline. It is not a count of patients and not a single measure of overall clinical status. A gene is included if it meets both a statistical criterion and a fold-change criterion: an FDR-adjusted p-value < 0.01 and fold change at most -1.3 or at least 1.3. The criteria include changes in either direction. The reported endpoint is the total number meeting the rule, not a statement that every included gene has the same biological importance.
General: differential expression methods compare observed expression patterns between conditions while accounting for features of count data. A p-value criterion addresses evidence against a null model, while a fold-change criterion restricts attention to changes of a specified size. An FDR adjustment is intended to address the multiplicity that arises when many genes are tested. The record supplies the threshold used, but does not report further details of the adjustment or the full statistical model.
Why use an FDR adjustment?
General: testing many genes creates many opportunities for apparently notable results by chance. An FDR procedure is designed to control the expected proportion of false discoveries among findings declared significant under the procedure’s assumptions. This differs from controlling the chance of at least one false positive across all tests. The registry’s stated FDR-adjusted p-value threshold is part of the rule for classifying genes, but the record does not report a complete multiplicity strategy for the clinical and biomarker secondary outcomes.
The fold-change thresholds also matter. They mean that statistical evidence alone is not enough for a gene to be counted as deregulated; the expression change must also meet the specified magnitude threshold in either direction. General: applying both kinds of criteria can make the endpoint more selective, but the count can still depend on the measurement process, analysis choices and population included. The registry does not report gene-level estimates, uncertainty intervals, or the resulting totals at each time point.
How should repeated time points be understood?
The registry lists baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12). The endpoint compares post-treatment measurements with baseline at each time point. General: measurements at multiple time points can describe how an outcome varies over follow-up, but testing or interpreting several time points raises questions about multiplicity and the intended primary comparison. The registry record does not report whether a particular time point was designated as the principal analysis, whether time points were tested jointly, or whether adjustment across time points was planned.
The secondary outcome list includes percentage changes in C-reactive protein, faecal calprotectin and faecal lactoferrin from baseline to Week 12, clinical remission at Week 12, and drug-related adverse events. The registry defines remission as Mayo Score at most 2 points, with all subscores at most 1 point. The outcome definitions identify what was to be assessed; they do not provide numerical results or explain how missing measurements were handled.
What do the planning assumptions mean?
The registry’s planning assumptions describe illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe the effect to detect as a stated fraction of the observed effect. Such calculations concern hypothetical future planning; they are not observed power and do not change the fact that this trial is listed as single group. The assumptions also refer to two arms, unlike the trial’s recorded design. Specific resulting planning values are not reported in the registry record.
General: a sample-size calculation depends on the target effect, outcome variability, significance level, allocation and analysis method. A planning calculation cannot show how likely the completed study was to detect an effect unless its assumptions and observed data are considered appropriately. The registry record does not report a sponsor sample-size justification, the planned statistical analysis details beyond the gene-analysis description, or interim analyses. Those details should not be inferred from a planning illustration.
Finally, the primary outcome population is described as a completers analysis set. The definition refers to completion of trial medication through the end-of-trial visit, a baseline and at least one post-baseline measurement for any clinical efficacy or biomarker endpoint, and no important protocol deviation flagged for exclusion or rescue use on or after Visit 1b. The registry text available for the definition ends before its final condition is complete, so the rest of the population rule is not reported in the registry record. The number included in that analysis set is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary molecular outcome involves many genes: the registry states that 60,675 were evaluated and 40,586 entered differential expression analyses. It defines a deregulated gene using an FDR-adjusted p-value < 0.01 alongside a fold-change threshold. This is a stated adjustment within the gene-expression analysis. The record does not explain whether or how multiplicity was handled across the separate clinical and biomarker outcomes, across time points, or across all trial objectives.
The registry lists secondary outcomes for percentage changes in C-reactive protein, faecal calprotectin and faecal lactoferrin from baseline to Week 12, clinical remission at Week 12, and drug-related adverse events. Their outcome definitions do not specify a hierarchy of testing or an adjustment method. The results are not reported in the registry record, and the statistical analysis plan is not reported in the registry record.
The primary endpoint population is labeled a completers analysis set. Its description requires completion of trial medication through the end-of-trial visit, baseline and at least one post-baseline measurement for any clinical efficacy or biomarker endpoint, and no important protocol deviation flagged for exclusion or rescue use on or after Visit 1b. The registry definition is cut off before its final condition is complete. The size of the analysis set and the number of participants contributing at each time point are not reported in the registry record.
Missing-data methods, rules for handling incomplete RNA sequencing measurements, and sensitivity analyses are not reported in the registry record. General: restricting an analysis to completers can make the analyzed population differ from the group initially enrolled, while handling missing observations through other methods depends on assumptions about why data are missing. Without the analysis details and outcome-level denominators, the effect of missing measurements on interpretation cannot be assessed.
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 1200 mg Intravenous (i.v.) | 2 | 8 | 25.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Spesolimab 1200 mg Intravenous (i.v.) | 0 of 8 |
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 1200 mg Intravenous (i.v.) | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Spesolimab 1200 mg Intravenous (i.v.) |
|---|---|---|
| Colitis | Gastrointestinal disorders | 1 of 8 |
| Diverticulitis | Infections and infestations | 1 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Spesolimab 1200 mg Intravenous (i.v.) |
|---|---|---|
| Nasopharyngitis | Infections and infestations | 4 of 8 |
| Eye inflammation | Eye disorders | 2 of 8 |
| Headache | Nervous system disorders | 2 of 8 |
| Iron deficiency anaemia | Blood and lymphatic system disorders | 1 of 8 |
| Conjunctival haemorrhage | Eye disorders | 1 of 8 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 8 |
| Colitis ulcerative | Gastrointestinal disorders | 1 of 8 |
| Dyspepsia | Gastrointestinal disorders | 1 of 8 |
| Fatigue | General disorders | 1 of 8 |
| Gastrointestinal infection | Infections and infestations | 1 of 8 |
Serious events with the highest arm-level rate: colitis (12.5%), diverticulitis (12.5%).
The registry lists one spesolimab group, titled Spesolimab 1200 mg Intravenous (i.v.), with 8 participants at risk for serious adverse events. Serious adverse events are recorded for 2 participants. The top serious terms listed are Colitis at 12.5% and Diverticulitis at 12.5%. The record lists 8 participants at risk for other adverse events and 8 affected, and lists deaths as 0.
These entries are descriptive counts from the trial’s single group. The serious-event terms are reported as terms, not as evidence that spesolimab caused them. The registry does not provide a comparator group, so these figures do not estimate a difference in safety relative to another treatment or to no treatment. The record’s listed percentage for each serious term should be read as reported, not recalculated or treated as a comparative risk.
General: adverse-event counts describe events or affected participants according to the registry’s reporting definitions. A count alone does not communicate severity beyond the category used, timing, duration, relatedness assessment, or uncertainty. Apart from the listed figures and terms, those details are not reported in the registry record. Given the single-group design, the safety entries are a description of observations during the study, not a causal comparison.
12. What the Result Does, and Does Not, Mean
The registry record identifies an exploratory phase 2 study of spesolimab in patients with active ulcerative colitis. Its primary question concerns gene-expression changes in mucosal biopsies over time, and its stated method defines which genes count as deregulated. The record does not report the resulting gene counts. It therefore documents an endpoint and analysis threshold, but does not show the numerical molecular findings needed to characterize the observed changes.
The listed secondary outcomes extend to biomarkers, clinical remission and adverse events. Their definitions indicate what the trial intended to assess, but their numerical results are not reported in the registry record. The safety entries include serious adverse events, named serious terms, other adverse events and deaths. Because there is no separate control group, those observations do not establish how the safety profile compares with another intervention.
General: a within-group change can be informative for describing what happened during follow-up, but it is not equivalent to a randomized comparison. Without a control group, time-related changes and other influences cannot be separated from a treatment effect using the design alone. A molecular endpoint can support exploration of biological response, but it does not itself establish a clinical effect.
The registry states an enrollment of 8. That context is important when reading descriptive counts: estimates from a small group can be imprecise, and each reported event or measurement can have a substantial influence on the overall description. The registry does not provide confidence intervals or numerical outcome estimates with which to assess precision for the primary or listed secondary outcomes.
The record also gives hypothetical planning assumptions involving a two-arm calculation, despite describing the completed study as single group. Those assumptions should not be mistaken for an observed result or for evidence that a treatment effect was demonstrated. Overall, the registry supports understanding the study’s design, objectives, endpoint definitions and listed safety observations. It does not report enough outcome data to quantify clinical or molecular effects or to support a comparative conclusion.
13. Why This Trial Matters Statistically
This trial is statistically notable for connecting an exploratory mechanism-of-action objective with RNA sequencing of mucosal biopsies. Rather than reducing the primary question to a single clinical score, the endpoint counts genes meeting prespecified statistical and fold-change criteria at multiple times. The record names the analysis method, the number of genes evaluated and the threshold used to classify deregulation. Those details help define what the endpoint means, even though the observed counts are not reported in the registry record.
The trial also illustrates why design and outcome should be read together. A single-group, unmasked study can describe measurements during treatment, but it cannot provide the same comparison as a randomized controlled design. The absence of a comparator matters both for interpreting changes from baseline and for understanding safety counts. In general, an observed change over time does not alone identify what would have happened without treatment.
The multiplicity context is especially relevant in gene-expression analysis, where many genes are evaluated. The registry’s use of an FDR-adjusted threshold recognizes this issue within the molecular outcome. However, the record does not describe a broader approach to multiplicity across outcomes and time points. This distinction helps readers avoid assuming that adjustment for gene-level testing answers every question about multiple analyses.
The listed secondary measures show that the exploratory scope included biomarkers, clinical remission and tolerability as well as gene expression. Keeping molecular and clinical endpoints conceptually separate is important: a molecular count is not interchangeable with a patient-level clinical outcome. Because numerical results for these outcomes are not reported in the registry record, their relationships cannot be evaluated from the record.
Finally, the trial’s planning assumptions describe a hypothetical two-arm sample-size illustration, while the registered trial design is single group. Recognizing that mismatch prevents a planning calculation from being mistaken for a description of the trial’s design or its observed power. The record is useful for examining endpoint construction and reporting limitations, but it does not provide the estimates needed to judge the precision of the trial’s results.
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 central limitation for interpreting results is that numerical primary outcome findings are not reported in the registry record. The record describes the gene-expression method and decision thresholds, but not the number of genes classified as deregulated at each time point. Numerical results for the listed secondary outcomes are also not reported in the registry record.
The trial is listed as single group, with allocation recorded as NA and masking as none. There is no randomized comparator, so the design cannot establish a between-group treatment effect. This also limits interpretation of within-group changes and safety events, which cannot be placed in comparative context from the registry record.
Enrollment was 8. That small group limits how much precision can ordinarily be expected from descriptive estimates, but the registry does not report confidence intervals or enough outcome-level information to quantify precision. The numbers contributing to each endpoint and time point are not reported in the registry record.
The endpoint population is described as a completers analysis set, but the registry definition ends before its final condition is complete. The size of that analysis set, the missing-data approach and any sensitivity analyses are not reported in the registry record. The number of analyses is listed as 0, and a full statistical analysis plan is not reported in the registry record.
The gene-level FDR threshold is stated, but multiplicity handling across outcomes and time points is not reported in the registry record. The record also does not report gene-level estimates or uncertainty intervals. Its sample-size assumptions describe a hypothetical two-arm calculation and do not match the listed single-group design; specific planning results are not reported in the registry record. These gaps mean the available record is more informative about intended measurement and analysis than about the precision or comparative meaning of observed outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: This Study Tests How BI 655130 Works in Patients With Active Ulcerative Colitis. The Study Also Tests How Well BI 655130 is Tolerated and Whether it Helps the Patients — NCT03100864.
- Registry record last updated 2025-10-16; status last verified 2025-10.
- Results first posted 2020-11-16.
- 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 completed phase 2 study examined spesolimab (BI 655130) in patients with active ulcerative colitis. The registry describes a single-group, unmasked design, with enrollment of 8 and an intervention group receiving spesolimab 1200 mg intravenously.
The primary endpoint was the number of genes classified as deregulated in mucosal biopsy RNA sequencing when post-treatment measurements were compared with baseline. The registry lists measurements through day 85 (week 12), describes DESeq2 analysis, and gives FDR and fold-change criteria. It also lists secondary biomarker, clinical remission and safety outcomes.
Numerical results for the primary and secondary outcomes are not reported in the registry record. The record lists serious adverse events affecting 2 participants, Colitis and Diverticulitis at 12.5% each, other adverse events affecting 8 participants, and deaths as 0. With no randomized comparator, the trial’s observations do not provide a comparative treatment estimate.