BI 655130 (SPESOLIMAB) induction treatment in patients with moderate-tosevere ulcerative colitis

• Register: EUCTR
• Last refreshed on: 7 September 2020
• Main ID: EUCTR2017-004230-28-DE
• Date of registration: 31/01/2018
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim Pharma GmbH & Co. KG
• Public title: BI 655130 (SPESOLIMAB) induction treatment in patients with moderate-tosevere ulcerative colitis
• Scientific title: A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of BI 655130 (SPESOLIMAB) Induction Therapy in patients with moderate-to-severely active ulcerative colitis who have failed previous biologics therapy
• Date of first enrolment: 04/06/2018
• Target sample size: 550
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004230-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Canada, China, Czech Republic, Denmark, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Boehringer Ingelheim International GmbH

• Name: Clinical Trial Information Desk
• Affiliation: Boehringer Ingelheim International GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. 18 - 75 years, at date of signing informed consent, males or females
2. Diagnosis of ulcerative colitis = 3 months prior to screening by clinical
and endoscopic evidence corroborated by a histopathology report
3. 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)
4. Endoscopic activity extending proximal to the rectum (= 15 cm from
anal verge)
5.Well-documented demonstration of inadequate response or loss of
response or have had unacceptable side effects with approved doses of
TNF? agonists (infliximab, adalimumab, golimumab) and/or
vedolizumab in the past as per definition in the CTP Appendix 10.6
6. May be receiving a therapeutic dose of the following:
- Oral 5-ASA compounds, provided that dose has been stable for at least
the 4 weeks immediately prior to randomisation, and/or
- Oral corticosteroids (= 20 mg per day of prednisone or equivalent),
provided that dose has been stable for the 2 weeks immediately prior to
randomisation, and/or
- Oral budesonide (= 9 mg per day ) or beclomethasone dipropionate (= 5 mg per day), provided that dose has been stable for the 2 weeks
immediately prior to randomisation, and/or
- Azathioprine, 6-MP or methotrexate, provided that dose has been
stable for the 8 weeks immediately prior to randomisation.
- Probiotics (e.g. S. boulardii) provided that dose has been stable for the
4 weeks immediately prior to randomisation.
7. Patients with extensive colitis or pancolitis of >10 years duration or
family history of colorectal cancer or personal history of increased
colorectal cancer risk must have had a negative colorectal cancer
screening within <1 year prior to enrolment (otherwise to be done
during screening colonoscopy).
8. Women of childbearing potential (WOCBP) must be ready to use
highly effective methods of birth control per ICH M3 (R2) that result in a
low failure rate of less than 1% per year when used consistently and
correctly.
9. Signed and dated written informed consent for 1368.5, in accordance
with GCP and local legislation prior to admission into the trial
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Evidence of abdominal abscess at screening
2. Evidence of fulminant colitis or toxic megacolon at screening
3. Ileostomy, colostomy, or known fixed symptomatic stenosis of the
intestine
4. Treatment with:
•any non-biologic medication (e.g. cyclosporine, tacrolimus or mycophenolate mofetil, intavenous corticosteroids, tofacitinib),
•any biologic treatment with a TNFa antagonist (adalimumab, infliximab, golimumab, certolizumab) or vedolizumab within 8 weeks prior to randomisation. (If drug level testing for previously used biologic treatment confirms no detectable drug level before randomization,
patient can be enrolled despite not having completed 8 weeks from last treatment.)
•any previous treatment with an approved dose of ustekinumab where
locally approved and available.
•rectal 5-ASA, parenteral or rectal corticosteroids (incl. budesonide) within 2 weeks prior to screening
•any investigational non-biologic drug for UC (including but not limited to JAK inhibitors, S1P modulators) within 30 days prior to randomisation
•any investigational biologic for UC (including IL-12 and IL-23 inhibitors; etrolizumab) within 8 weeks. (If drug level testing for previously used biologic treatment confirms no detectable drug level before randomization, patient can be enrolled despite not having completed 8 weeks from last treatment.)
•any prior exposure to BI 655130, natalizumab or rituximab
5. Positive stool examinations for C. difficile (toxin A/B – test positive) or other intestinal
pathogens < 30 days prior to screening
6. have had previous surgery or are anticipated to require surgical intervention for UC
7. Evidence of colonic moderate/severe mucosal dysplasia or colonic adenomas, unless properly removed
8. Primary sclerosing cholangitis
9. Faecal transplant = 30 days prior to randomisation
10. Increased risk of infectious complications (e.g. recent pyogenic infection, any congenital or acquired immunodeficiency (e.g. HIV), past organ or stem cell transplantation)
11. Live or attenuated vaccination within 6 weeks prior to screening
12. Active or latent TB: Patients with a positive TB test during screening
are excluded, unless:
•Patient had previous diagnosis of active or latent TB and has completed appropriate treatment per local practise /guidelines within the last 3 years and at least 6 months before first administration of Trial medication under this protocol (patients may be re-screened once to
meet this criterion)
•A positive QuantiFERON TB (Patients with suspected false positive or indeterminate QuantiFERON TB result may be re-tested once)
•If Quantiferon not available or providing indeterminate results after repeat testing tuberculin skin test should be performed : Tuberculin Skin test positive reaction =10mm (=5mm if receiving =15mg/d prednisone or its equivalent)
13. Relevant chronic or acute infections including active tuberculosis, human immunodeficiency virus (HIV) infection or viral hepatitis. A patient can be re-screened if the patient was treated and is cured from the acute infection.
14. Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma or squamous cell carcinoma of the skin, or history of cervical cancer in situ (treated >3years); patients with remote history of malignancy (=5 years prior) may be considered and have to be discussed with sponsor case-by-case
15. Major surgery (major according

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Moderate-to-severely active ulcerative colitis
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

Intervention(s)

Product Name: Spesolimab
Product Code: BI 655130
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Spesolimab
Current Sponsor code: BI 655130
Other descriptive name: MONOCLONAL ANTIBODY ANTI-IGG1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Product Name: Spesolimab
Product Code: BI 655130
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: SPESOLIMAB
Current Sponsor code: BI 655130
Other descriptive name: MONOCLONAL ANTIBODY ANTI-IGG1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: - To prove the concept of clinical activity of BI 655130 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)

Secondary Objective: - To confirm efficacy and safety of BI 655130 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 the randomised withdrawal study 1368- 0020.

Primary end point(s): 1. Part 1 and Part 2: Proportion of patients with Clinical Remission at week 12 (defined as mMCS SFS=0 or 1, if drop =1 from BL; and RBS=0; and mESS=1)

Timepoint(s) of evaluation of this end point: 1. Week 12

Secondary Outcome(s)

Secondary end point(s): 1. Part 2/Phase III only: Proportion of patients with Mucosal Healing at week 12 (defined as mESS = 1)
2. Part 2/Phase III only: Change in IBDQ score from baseline at week 12
3. Part 1 and Part 2: Proportion of patients with combined Mucosal healing and histologic remission at week 12 (defined as mESS = 1 and Robarts Histology Index = 6)
4. Part 2/Phase II only: Proportion of patients with Mucosal Healing at week 12
5. Part 2/Phase II only: Proportion of patients with Clinical response at week 12

Timepoint(s) of evaluation of this end point: 1. Week 12
2. Week 0 and Week 12
3. Week 12
4. Week 12
5. Week 12

Secondary ID(s)

1368-0005

2017-004230-28-AT

Source(s) of Monetary Support

Boehringer Ingelheim Pharma GmbH & Co. KG

Ethics review

Status: Approved
Approval date: 24/05/2018
Contact: