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

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

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.

Study Overview

• Status: Completed
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: Placebo; Drug: Spesolimab

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria, A-4010
    • Ordensklinikum Linz GmbH - Barmherzige Schwestern
  • Vienna, Austria, 1090
    • AKH - Medical University of Vienna
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • Centre Hospitalier Universitaire de Liege
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • University of Manitoba - Health Sciences Centre
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Victoria Hospital (LHSC)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen, AöR
  • Erlangen, Germany, 91054
    • Universitatsklinikum Erlangen
  • Essen, Germany, 45147
    • Universitätsklinikum Essen AöR
  • Esslingen, Germany, 73730
    • Klinikum Esslingen GmbH
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein, Campus Kiel
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm
• Italy
  • Padova, Italy, 35128
    • Azienda Ospedaliera Universitaria di Padova
  • Rozzano (MI), Italy, 20089
    • Istituto Clinico Humanitas
• Japan
  • Chiba, Sakura, Japan, 285-8741
    • Toho University Sakura Medical Center
  • Hokkaido, Sapporo, Japan, 004-0041
    • Sapporo Tokushukai Hospital
  • Hokkaido, Sapporo, Japan, 065-0033
    • Sapporo Higashi Tokushukai Hospital
  • Hyogo, Nishinomiya, Japan, 663-8501
    • Hyogo College of Medicine Hospital
  • Kagoshima, Kagoshima, Japan, 892-0846
    • Sameshima Hospital
  • Kanagawa, Kamakura, Japan, 247-0056
    • Ofuna Chuo Hospital
  • Tokyo, Bunkyo-ku, Japan, 113-8519
    • Tokyo Medical and Dental University
  • Tokyo, Minato-ku, Japan, 108-8642
    • Kitasato Institute Hospital
  • Tokyo, Shinjuku, Japan, 169-0073
    • Tokyo Yamate Medical Center
• Korea, Republic of
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Medical Center
• Poland
  • Warsaw, Poland, 02-507
    • Central Clinical Hospital MSWiA, Internal Diseases, Warsaw
  • Warsaw, Poland, 00-632
    • Health Center of Mother, Child and Youth Sp.z o.o.
• Russian Federation
  • Irkutsk, Russian Federation, 664003
    • FSB Instit. HC Irkutsk Scient.Cent. Sibirian Branch of Russ. Acad. Scien.
  • Kirov, Russian Federation, 610027
    • Kirov State Med.Univ. of MoH RF
  • Moscow, Russian Federation, 123423
    • Federal State Budgetary Institution " State Scientific Center of Coloproctology" MOH Russia
  • Moscow, Russian Federation, 129110
    • Reg. Clin. Scientific Research Institute na Vladimiskiy
  • Pyatigorsk, Russian Federation, 357502
    • The limited liability company "Clinic USI 4D"
  • Saint-Petersburg, Russian Federation, 194044
    • FSBMEI HPE "Military Medical Academy n.a. S.M. Kirov"
• Spain
  • Sevilla, Spain, 41013
    • Hospital Virgen del Rocio
  • Valencia, Spain, 46026
    • Hospital Politècnic La Fe
• United Kingdom
  • Barnsley, United Kingdom, S75 2EP
    • Barnsley Hospital
  • Doncaster, United Kingdom, DN2 5LT
    • Doncaster Royal Infirmary
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • Prescot, United Kingdom, L35 5DR
    • Whiston Hospital
• United States
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut, LLC
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32803
      • AdventHealth Orlando
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Decatur, Georgia, United States, 30033
      • Atlanta Center for Gastroenterology, P.C.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center-New York Presbyterian Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Digestive Disease Specialists Inc
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • Southern Star Research Institute, LLC
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants - Southlake
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1- Placebo Group	Drug: Placebo; Solution for infusion
Experimental: Group 2- Small Dose Group	Drug: Spesolimab; Solution for infusion
Experimental: Group 3- Medium Dose Group	Drug: Spesolimab; Solution for infusion
Experimental: Group 4 - High Dose Group	Drug: Spesolimab; Solution for infusion

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2018
• Primary Completion (Actual): May 18, 2020
• Study Completion (Actual): May 18, 2020

Study Registration Dates

• First Submitted: March 15, 2018
• First Submitted That Met QC Criteria: March 28, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): June 11, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: 1368-0005; 2017-004230-28 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No