E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate-to-severely active ulcerative colitis |
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E.1.1.1 | Medical condition in easily understood language |
Moderate-to-severely active ulcerative colitis |
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E.1.1.2 | Therapeutic area | Body processes [G] - Digestive System and Oral Physiological Phenomena [G10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045365 |
E.1.2 | Term | Ulcerative colitis |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- 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) |
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E.2.2 | Secondary objectives of the trial |
- 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 TNFɑ 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 |
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E.4 | Principal 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 TNFα 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 to the investigator's assessment) performed within 12 weeks prior to randomization or planned during study conduct, e.g. hip replacement.
16. Pathological safety lab parameters: haemoglobin < 9 g/dL, total white blood count (WBC) < 3000 cells/μl, neutrophils < 1000 cells/μl, thrombocytes < 100.000/μl, creatinine ≥ 2 mg/dL, total bilirubin > 2 x ULN with ratio of direct/indirect >1 (patients with Gilbert's syndrome are not excluded), Alkaline Phosphatase >3 x ULN. – measured and
confirmed by Central laboratory at screening visit.
17. Currently enrolled in another investigational device or drug study.
18. Women who are pregnant, nursing, or who plan to become pregnant while in the trial
19. Evidence of a current or previous disease, medical condition (including chronic alcohol or drug abuse) other than ulcerative colitis, surgical procedure, medical examination finding (including vital signs and electrocardiogram (ECG)), or laboratory value at the screening visit outside the reference range that in the opinion of the investigator is
clinically significant and would make the study participant unreliable to adhere to the protocol or to complete the trial, compromise the safety of the patient, or compromise the quality of the data
20. Any psychiatric or social problems possibly interfering with ability to comply with all study visits/procedures
21. History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients.
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E.5 End points |
E.5.1 | 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) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | 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
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers associated with Ulcerative Colitis and the IL-36R pathway |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 4 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 4 |