Colitis, Ulcerative
Conditions
Brief summary
The primary objective of this trial is to understand the mechanism of action of BI655130 in patients with UC Secondary objectives are to explore clinical effect, safety and tolerability (including immunogenicity) of BI 655130 treatment
Interventions
DRUGSpesolimab
12 weeks treatment
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 18 - 75 years at screening * Diagnosis of UC \>= 3 months prior to screening. * Moderately to severely active UC as confirmed by Mayo Score ≥6 * Receiving conventional, non-biologic therapy for UC. * Negative colon cancer screening * Further inclusion criteria apply
Exclusion criteria
* Prior use of any biological treatment in the past (e.g.integrin inhibitors, IL12/23 or IL23 inhibitors, any investigational biological drugs) * Extensive colonic resection * Evidence of infection with C. difficile or other intestinal pathogen \< 30 days prior to screening * Active or latent tuberculosis * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Measurements done at baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12). | 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. A total of 60,675 genes were evaluated, 40,586 genes were included in the differential expression analyses. Based on the raw read count values the DESeq2 method, one of the standard methods to analyse RNAseq data, was used for the gene expression analysis and to identify deregulated genes. A gene was considered deregulated with a FDR (false discovery rate) adjusted p-value \< 0.01 and a fold change ≤ -1.3 or ≥ 1.3. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in C-reactive Protein (CRP) From Baseline to Week 12 | Measurements done at baseline (day -8 to -6) and week 12 (day 85). | Percent change in C-reactive protein (CRP) from baseline to Week 12 (day 85). |
| Percent Change in Faecal Calprotectin From Baseline to Week 12 | Measurements done at baseline (day -8 to -6) and week 12 (day 85). | Percent change in faecal calprotectin from baseline to week 12 (day 85). |
| Percent Change in Faecal Lactoferrin From Baseline to Week 12 | Measurements done at baseline (day -8 to -6) and week 12 (day 85). | Percent change in faecal lactoferrin from baseline to week 12 (day 85). |
| Number of Participants With Clinical Remission (Defined as Mayo Score ≤2 Points, and All Subscores ≤1 Point) at Week 12 | Week 12 (day 85) following start of treatment. | Number of participants with clinical remission (defined as Mayo score ≤2 points, and all subscores ≤1 point) at Week 12. The Mayo score is a composite disease activity score consisting of 4 items or subscores: stool frequency (relative to normal), rectal bleeding, physician's global assessment (PGA), and endoscopic appearance. The overall range of the Mayo score was 0 to 12 (higher scores being worse) and each subscore had a range of 0 to 3. |
| Number of Patients With Drug Related Adverse Events (AEs) | Date of start of infusion of first study drug (Day 1) till the date of end of infusion of last study drug (day 57) + 140 days at 11:59 p.m., up to 197 days. | Number of patients with drug related adverse events (AEs) during the on-treatment period. |
Countries
Belgium, Germany, United Kingdom
Participant flow
Recruitment details
This was an Phase IIa multi-centre, non-randomised, uncontrolled single arm), open-label, exploratory trial to assess biomarker changes in response to Interleukin-36 signalling blockade induced by treatment with spesolimab in patients with moderate to severe active Ulcerative colitis.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Spesolimab 1200 mg Intravenous (i.v.) 1200 milligram Spesolimab (infusion solution, BI 655130) was given for 12 weeks intravenously with a concentration of 20 milligram/milliliter every four weeks (on Day 1, Week 4, and Week 8). | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Spesolimab 1200 mg Intravenous (i.v.) |
|---|---|
| Age, Continuous | 43.1 years STANDARD_DEVIATION 19.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 2 / 8 |
Outcome results
Primary
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
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. A total of 60,675 genes were evaluated, 40,586 genes were included in the differential expression analyses. Based on the raw read count values the DESeq2 method, one of the standard methods to analyse RNAseq data, was used for the gene expression analysis and to identify deregulated genes. A gene was considered deregulated with a FDR (false discovery rate) adjusted p-value \< 0.01 and a fold change ≤ -1.3 or ≥ 1.3.
Time frame: Measurements done at baseline (day -8 to -6), day 1, day 4, day 15, day 57 and day 85 (week 12).
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Spesolimab 1200 mg Intravenous (i.v.) | 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 | Change from baseline to Day 1 | 3 deregulated genes |
| Spesolimab 1200 mg Intravenous (i.v.) | 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 | Change from baseline to Day 4 | 5 deregulated genes |
| Spesolimab 1200 mg Intravenous (i.v.) | 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 | Change from baseline to Day 15 (week 2) | 2 deregulated genes |
| Spesolimab 1200 mg Intravenous (i.v.) | 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 | Change from baseline to Day 57 (week 8) | 7 deregulated genes |
| Spesolimab 1200 mg Intravenous (i.v.) | 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 | Change from baseline to Day 85 (week 12) | 9 deregulated genes |
Secondary
Number of Participants With Clinical Remission (Defined as Mayo Score ≤2 Points, and All Subscores ≤1 Point) at Week 12
Number of participants with clinical remission (defined as Mayo score ≤2 points, and all subscores ≤1 point) at Week 12. The Mayo score is a composite disease activity score consisting of 4 items or subscores: stool frequency (relative to normal), rectal bleeding, physician's global assessment (PGA), and endoscopic appearance. The overall range of the Mayo score was 0 to 12 (higher scores being worse) and each subscore had a range of 0 to 3.
Time frame: Week 12 (day 85) following start of treatment.
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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Spesolimab 1200 mg Intravenous (i.v.) | Number of Participants With Clinical Remission (Defined as Mayo Score ≤2 Points, and All Subscores ≤1 Point) at Week 12 | 0 Participants |
Secondary
Number of Patients With Drug Related Adverse Events (AEs)
Number of patients with drug related adverse events (AEs) during the on-treatment period.
Time frame: Date of start of infusion of first study drug (Day 1) till the date of end of infusion of last study drug (day 57) + 140 days at 11:59 p.m., up to 197 days.
Population: Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Spesolimab 1200 mg Intravenous (i.v.) | Number of Patients With Drug Related Adverse Events (AEs) | 6 Participants |
Secondary
Percent Change in C-reactive Protein (CRP) From Baseline to Week 12
Percent change in C-reactive protein (CRP) from baseline to Week 12 (day 85).
Time frame: Measurements done at baseline (day -8 to -6) and week 12 (day 85).
Population: Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Spesolimab 1200 mg Intravenous (i.v.) | Percent Change in C-reactive Protein (CRP) From Baseline to Week 12 | -79.6 percentage change (%) |
Secondary
Percent Change in Faecal Calprotectin From Baseline to Week 12
Percent change in faecal calprotectin from baseline to week 12 (day 85).
Time frame: Measurements done at baseline (day -8 to -6) and week 12 (day 85).
Population: Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Spesolimab 1200 mg Intravenous (i.v.) | Percent Change in Faecal Calprotectin From Baseline to Week 12 | 13.0 percentage change (%) |
Secondary
Percent Change in Faecal Lactoferrin From Baseline to Week 12
Percent change in faecal lactoferrin from baseline to week 12 (day 85).
Time frame: Measurements done at baseline (day -8 to -6) and week 12 (day 85).
Population: Safety analysis set (SAF): This patient set included all entered patients who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Spesolimab 1200 mg Intravenous (i.v.) | Percent Change in Faecal Lactoferrin From Baseline to Week 12 | 0.4 percentage change (%) |