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

Phase 2

Completed

Conditions: Colitis, Ulcerative

Interventions: Drug: Placebo
Drug: Spesolimab

Registration Number: NCT03482635

Lead Sponsor: Boehringer Ingelheim

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 98

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1- Placebo Group	Placebo	-
Group 3- Medium Dose Group	Spesolimab	-
Group 4 - High Dose Group	Spesolimab	-
Group 2- Small Dose Group	Spesolimab	-

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With Clinical Remission at Week 12	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.

Secondary Outcome Measures

Name	Time	Method
Proportion of Patients With Clinical Response at Week 12	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.
Proportion of Patients With Combined Endoscopic Improvement and Histologic Remission at Week 12	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.
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) Score From Baseline at Week 12	At baseline and 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.
Proportion of Patients With Endoscopic Improvement at Week 12	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.

Trial Locations

Locations (54): University of Manitoba - Health Sciences Centre
🇨🇦
Winnipeg, Manitoba, Canada
FSB Instit. HC Irkutsk Scient.Cent. Sibirian Branch of Russ. Acad. Scien.
🇷🇺
Irkutsk, Russian Federation
Medizinische Hochschule Hannover
🇩🇪
Hannover, Germany
Kirov State Med.Univ. of MoH RF
🇷🇺
Kirov, Russian Federation
FSBMEI HPE "Military Medical Academy n.a. S.M. Kirov"
🇷🇺
Saint-Petersburg, Russian Federation
Universitätsklinikum Schleswig-Holstein, Campus Kiel
🇩🇪
Kiel, Germany
Reg. Clin. Scientific Research Institute na Vladimiskiy
🇷🇺
Moscow, Russian Federation
Universitätsklinikum Aachen, AöR
🇩🇪
Aachen, Germany
Sapporo Higashi Tokushukai Hospital
🇯🇵
Hokkaido, Sapporo, Japan
Centre Hospitalier Universitaire de Liège
🇧🇪
Liège, Belgium
AdventHealth Orlando
🇺🇸
Orlando, Florida, United States
Texas Digestive Disease Consultants - Southlake
🇺🇸
Southlake, Texas, United States
Medical Research Center of Connecticut, LLC
🇺🇸
Hamden, Connecticut, United States
Victoria Hospital (LHSC)
🇨🇦
London, Ontario, Canada
UZ Leuven
🇧🇪
Leuven, Belgium
Columbia University Medical Center-New York Presbyterian Hospital
🇺🇸
New York, New York, United States
AKH - Medical University of Vienna
🇦🇹
Vienna, Austria
Hunter Holmes McGuire VA Medical Center
🇺🇸
Richmond, Virginia, United States
Ordensklinikum Linz GmbH - Barmherzige Schwestern
🇦🇹
Linz, Austria
Universitätsklinikum Erlangen
🇩🇪
Erlangen, Germany
Klinikum Esslingen GmbH
🇩🇪
Esslingen, Germany
Universitätsklinikum Essen AöR
🇩🇪
Essen, Germany
Universitätsklinikum Ulm
🇩🇪
Ulm, Germany
Azienda Ospedaliera Universitaria di Padova
🇮🇹
Padova, Italy
Ofuna Chuo Hospital
🇯🇵
Kanagawa, Kamakura, Japan
Sapporo Tokushukai Hospital
🇯🇵
Hokkaido, Sapporo, Japan
Istituto Clinico Humanitas
🇮🇹
Rozzano (MI), Italy
Hyogo College of Medicine Hospital
🇯🇵
Hyogo, Nishinomiya, Japan
Sameshima Hospital
🇯🇵
Kagoshima, Kagoshima, Japan
Tokyo Medical and Dental University
🇯🇵
Tokyo, Bunkyo-ku, Japan
Toho University Sakura Medical Center
🇯🇵
Chiba, Sakura, Japan
Kitasato Institute Hospital
🇯🇵
Tokyo, Minato-ku, Japan
Tokyo Yamate Medical Center
🇯🇵
Tokyo, Shinjuku, Japan
Inje University Haeundae Paik Hospital
🇰🇷
Busan, Korea, Republic of
Yeungnam University Medical Center
🇰🇷
Daegu, Korea, Republic of
Health Center of Mother, Child and Youth Sp.z o.o.
🇵🇱
Warsaw, Poland
Central Clinical Hospital MSWiA, Internal Diseases, Warsaw
🇵🇱
Warsaw, Poland
Hospital Virgen del Rocío
🇪🇸
Sevilla, Spain
The limited liability company "Clinic USI 4D"
🇷🇺
Pyatigorsk, Russian Federation
Doncaster Royal Infirmary
🇬🇧
Doncaster, United Kingdom
Federal State Budgetary Institution " State Scientific Center of Coloproctology" MOH Russia
🇷🇺
Moscow, Russian Federation
Hospital Politècnic La Fe
🇪🇸
Valencia, Spain
Barnsley Hospital
🇬🇧
Barnsley, United Kingdom
University of Miami
🇺🇸
Miami, Florida, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
Atlanta Center for Gastroenterology, P.C.
🇺🇸
Decatur, Georgia, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
University Hospitals of Cleveland
🇺🇸
Cleveland, Ohio, United States
Digestive Disease Specialists Inc
🇺🇸
Oklahoma City, Oklahoma, United States
Baylor College of Medicine
🇺🇸
Houston, Texas, United States
Southern Star Research Institute, LLC
🇺🇸
San Antonio, Texas, United States
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
Whiston Hospital
🇬🇧
Prescot, United Kingdom
Guy's Hospital
🇬🇧
London, United Kingdom