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

Phase 2

Completed

• Conditions: Colitis, Ulcerative
• Interventions: Drug: Placebo; Drug: Spesolimab

• Registration Number: NCT03123120
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-13
• Study First Submitted QC: 2017-04-18
• Study First Posted: 2017-04-21
• Study Start: 2017-06-07
• Primary Completion: 2020-03-26
• Study Completion: 2020-09-16
• Results First Submitted: 2021-09-15
• Results First Submitted QC: 2021-09-15
• Status Verified: 2021-10
• Results First Posted: 2021-10-07
• Last Update Submitted: 2021-10-15
• Last Update Posted: 2021-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

Not provided

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo was administered via intravenous infusion over 12 weeks of treatment.
Spesolimab	Spesolimab	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).

Primary Outcome Measures

Name	Time	Method
Proportion of Participants With Endoscopic Improvement (MCS mESS ≤1) at Week 12	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.

Secondary Outcome Measures

Name	Time	Method
Proportion of Participants With Total Clinical Remission (tCR) Based on Total Mayo Clinical Score at Week 12	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.
Proportion of Participants With Histological Remission at Week 12	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.
Proportion of Participants With Clinical Remission (CR) Based on Mayo Clinical Score at Week 12	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From first does of study medication until end of the follow-up period, up to 36 weeks.	Number of participants with any treatment-emergent adverse events (TEAEs) was reported.

Trial Locations

Locations (16)

Aalborg Sygehus Syd; 🇩🇰 Aalborg, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

Hospital Puerta de Hierro; 🇪🇸 Majadahonda, Spain

Universitätsklinikum Freiburg; 🇩🇪 Freiburg, Germany

Whiston Hospital; 🇬🇧 Prescot, United Kingdom

St James's University Hospital; 🇬🇧 Leeds, United Kingdom

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain

Hospital Politècnic La Fe; 🇪🇸 Valencia, Spain

Universitätsklinikum Schleswig-Holstein, Campus Kiel; 🇩🇪 Kiel, Germany

Sanos Clinic; 🇩🇰 Herlev, Denmark

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Universitätsklinikum Erlangen; 🇩🇪 Erlangen, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Germany

Akershus Universitetssykehus HF; 🇳🇴 Lørenskog, Norway

Amsterdam UMC, Locatie AMC; 🇳🇱 Amsterdam, Netherlands

Guy's Hospital; 🇬🇧 London, United Kingdom