A Study in Patients With Mild or Moderate Ulcerative Colitis Who Take a TNF Inhibitor. The Study Investigates Whether Bowel Inflammation Improves When Patients Take BI 655130 in Addition to Their Current Therapy

Study Overview
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Brief Summary
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The objectives of this trial are safety and efficacy (proof-of-concept) of induction of mucosal healing by BI 655130 add-on therapy in patients with mild or moderate ulcerative colitis and persisting endoscopic activity despite pre-existing TNFi treatment. This trial will explore safety and efficacy of a dose of BI 655130 that was modelled to achieve the similar exposures as the highest exposures tested and found safe and tolerable in preceding single and multiple dose studies in healthy subjects, as add-on to pre-existing TNFi (Tumor necrosis factor inhibitor) treatment. Secondary and further objectives include assessment of the pharmacokinetic (PK) profile of BI 655130 and early exploration of specific biomarkers with potential usefulness to predict clinical efficacy or safety outcome or help understand BI 655130's mode of action.

Official Title
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Proof-of-concept Study of BI 655130 add-on Treatment in Patients With Mild-to-moderately Active Ulcerative Colitis During TNF Inhibitor Therapy

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Spesolimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 18 - 75 years at screening and randomisation Diagnosis of ulcerative colitis >= 5 months prior to screening Receiving TNFi treatment with doses (i.e. dose and dosing interval) unchanged for >= 4 months (Infliximab) or >= 2 Monaten (Adalimumab or Golimumab) prior to randomisation Mild or moderate disease activity, defined as total Mayo Score (MCS) (<= 10) Further inclusion criteria apply Exclusion Criteria: Prior use of more than two different TNF inhibitors or vedolizumab Extensive colonic resection Evidence of infection with C. difficile or other intestinal pathogen <28 days prior to screening Active or latent tuberculosis Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Spesolimab<br>1200 milligrams (mg) of Spesolimab (BI 655130) were administered every 4 weeks (q4w) via intravenous infusion over 12 weeks of treatment (3 injections of Spesolimab 1200 mg in total during the 12 weeks: at Week 0, 4, and 8 respectively). | Drug: Spesolimab<br>* 12 weeks treatment<br>* Other names: BI 655130;|
| Placebo Comparator: Placebo<br>Matching placebo was administered via intravenous infusion over 12 weeks of treatment. | Drug: Placebo<br>* 12 weeks treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Endoscopic Improvement (MCS mESS ≤1) at Week 12 | Proportion of participants with endoscopic improvement (Mayo clinical score (MCS) modified endoscopic sub-score (mESS) ≤1) at Week 12 was reported. The endoscopic improvement (mucosal healing) was defined as the Mayo clinical score (MCS) modified endoscopic sub-score (mESS) ≤ 1 point. The MCS mESS ranged from 0 (normal) to 3 (severe disease). The mESS was assessed by a central reader who was independent from the investigator. The 95% confidence intervals (in the descriptive statistics part) were calculated using the method of Wilson. | At Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Total Clinical Remission (tCR) Based on Total Mayo Clinical Score at Week 12 | Proportion of participants with total clinical remission based on total Mayo clinical score at Week 12 was reported. The total clinical remission based on total Mayo clinical score was defined as the total Mayo clinical score ≤ 2 points and all sub-scores ≤ 1 point. The total Mayo clinical score was a composite disease activity score consisting of 4 sub-scores: stool frequency, rectal bleeding, physician's global assessment, and modified endoscopic appearance. Each sub-score ranged from 0 (normal) to 3 (severe disease/worse disease status). The total Mayo score was by summing up the four sub-scores and ranged from 0 to 12 with higher score indicating worse disease. The 95% confidence intervals (in the descriptive statistics part) were calculated using the method of Wilson. | At Week 12 | 
| Proportion of Participants With Histological Remission at Week 12 | Proportion of participants with histological remission at Week 12 was reported. The histological remission was defined as the Robarts histology index score ≤ 6. The Robarts histopathology index (RHI) was a histologic activity score, scoring the components chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium and erosion or ulceration on a scale of 0 to 3. The 4 components were weighted differently to calculate the RHI, with RHI = 1 × chronic inflammatory infiltrate level + 2 × lamina propria neutrophils + 3 × neutrophils in epithelium + 5 × erosion or ulceration. The resulting RHI score ranged from 0 (no disease activity) to 33 (severe disease activity). The 95% confidence intervals (in descriptive statistics part) were calculated using the method of Wilson. | At Week 12 | 
| Proportion of Participants With Clinical Remission (CR) Based on Mayo Clinical Score at Week 12 | Proportion of participants with clinical remission (CR) based on Mayo clinical score at Week 12 was reported. The clinical remission based on Mayo clinical score was defined as the total Mayo clinical Score ≤ 2 and Rectal Bleeding Subscore = 0, Stool Frequency Score =0 or 1 and drop ≥ 1 from baseline, and Modified endoscopic sub-score (mESS) ≤ 1. The total Mayo clinical score was a composite disease activity score consisting of 4 sub-scores: stool frequency, rectal bleeding, physician's global assessment, and modified endoscopic appearance. Each sub-score ranged from 0 (normal) to 3 (severe disease/worse disease status). The total Mayo clinical score was by summing up the four sub-scores and ranged from 0 to 12 with higher score indicating worse disease. The 95% confidence intervals (in the descriptive statistics part) were calculated using the method of Wilson. | At Week 12 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Number of participants with any treatment-emergent adverse events (TEAEs) was reported. | From first does of study medication until end of the follow-up period, up to 36 weeks. |