BI655130 (SPESOLIMAB) Induction Treatment in Patients With Moderate-to-severe Ulcerative Colitis

Study Overview
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Brief Summary
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This trial has two sequentially enrolling parts with different objectives. The primary objectives of this trial are to prove the concept of clinical activity of BI655130 (SPESOLIMAB) in patients with moderate-to-severely active ulcerative colitis who have failed previous biologic treatments and to identify efficacious and safe dose regimens in Part 1 (Phase II) to confirm efficacy and safety of BI655130 (SPESOLIMAB) in patients with moderate-to-severely active ulcerative colitis who have failed previous biologic treatments in Part 2 (Phase III) To provide, along with induction study 1368-0018 and the run-in cohort of 1368-0020, the target population to be evaluated in study 1368-0020.

Official Title
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A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of BI655130 (SPESOLIMAB) Induction Therapy in Patients With Moderate-to-severely Active Ulcerative Colitis Who Have Failed Previous Biologics 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 date of signing informed consent, males or females Diagnosis of ulcerative colitis ≥ 3 months prior to screening by clinical and endoscopic evidence corroborated by a histopathology report Moderate to severe activity (total MCS 6 to 12 with a RBS ≥ 1 AND an SFS ≥ 1 AND mESS ≥ 2 within 7-28 days prior to first dose) Endoscopic activity extending proximal to the rectum (≥ 15 cm from anal verge) Well-documented demonstration of inadequate response or loss of response or have had unacceptable side effects with approved doses of TNFɑ antagonists (infliximab, adalimumab, golimumab) and/or vedolizumab in the past (screening of both TNFɑ antagonists-AND-Vedolizumab failure patients will be capped once 48 randomized patients in Part 1 and 117 randomized patients in Part 2 meet this criterion; patients who have already been screened at the time of the cap will continue to be randomized into the study) Further inclusion criteria apply Exclusion Criteria: Evidence of abdominal abscess at screening Evidence of fulminant colitis or toxic megacolon at screening Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine 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: Group 1- Placebo Group<br> | Drug: Placebo<br>* Solution for infusion<br>|
| Experimental: Group 2- Small Dose Group<br> | Drug: Spesolimab<br>* Solution for infusion<br>|
| Experimental: Group 3- Medium Dose Group<br> | Drug: Spesolimab<br>* Solution for infusion<br>|
| Experimental: Group 4 - High Dose Group<br> | Drug: Spesolimab<br>* Solution for infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Clinical Remission at Week 12 | Proportion of patients with clinical remission (defined as modified Mayo Clinical Score (MCS) ≤ 2, with Stool Frequency Score (SFS) = 0 or 1 [if drop ≥1 from baseline] and Rectal Bleeding Score (RBS) = 0 and modified Endoscopic Subscore (mESS) ≤ 1) at week 12. Proportion of patients was calculated as n/N, with n=number of patients with clinical remission at week 12 and N=number analyzed. 95% Confidence Intervals (CI) were calculated using the method of Wilson. | At week 12. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Clinical Response at Week 12 | Proportion of patients with clinical response (defined as Rectal Bleeding Score (RBS) ≤ 1 or decrease by ≥1 from baseline; and total Mayo Clinical Score (MCS) decrease by ≥ 3 and 30% from baseline) at week 12. Proportion of patients is calculated as n/N, with n=number of patients with clinical response at week 12 and N=number of patients analyzed. 95% Confidence Intervals (CI) are calculated using the method of Wilson. | At week 12. | 
| Proportion of Patients With Endoscopic Improvement at Week 12 | Proportion of patients with endoscopic improvement at week 12 (defined as modified Endoscopic Subscore (mESS) ≤ 1) Proportion of patients was calculated as n/N, with n=number of patients with Endoscopic Improvment at Week 12 and N=number analysed. 95% Confidence Intervals (CI) were calculated using the method of Wilson. | At week 12. | 
| Proportion of Patients With Combined Endoscopic Improvement and Histologic Remission at Week 12 | Proportion of patients with combined endoscopic improvement and histologic remission at week 12 (defined as modified Endoscopic Subscore (mESS) ≤ 1 and Robarts Histology Index ≤ 6). Proportion of patients was calculated as n/N, with n= number of patients with Endoscopic Improvement and histologic remission at week 12 and N=number of patients analysed. | At week 12. | 
| Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline at Week 12 | Change in Inflammatory Bowel Disease Questionnaire (IBDQ) score from baseline at Week 12. The IBDQ is a 32-item self-report questionnaire for patients with IBD to evaluate the patient reported outcomes across 4 dimensions: bowel symptoms (loose stools, abdominal pain), systemic symptoms (fatigue, altered sleep pattern), social function (work attendance, need to cancel social events), and emotional function (anger, depression, irritability). The response options describe the magnitude or frequency of impairment from 1 (most severe) to 7 (no impairment). The items are summed up, resulting in a sum score ranging from 32 to 224 points, with higher scores indicating better outcomes. A score change of 16 is reported to reflect the minimal clinically important difference (MCID). Mean is adjusted mean. | At baseline and at week 12. |