Efficacy and Safety of Vedolizumab IV in the treatment of Primary Sclerosing Cholangitis in patients with Inflammatory Bowel Disease

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2014-003942-28-AT
• Date of registration: 24/03/2016
• Prospective Registration: Yes
• Primary sponsor: Takeda Development Centre Europe, Ltd.
• Public title: Efficacy and Safety of Vedolizumab IV in the treatment of Primary Sclerosing Cholangitis in patients with Inflammatory Bowel Disease
• Scientific title: Randomized, Global, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Vedolizumab IV for the Treatment of Primary Sclerosing Cholangitis, With Underlying Inflammatory Bowel Disease
• Date of first enrolment: 13/04/2016
• Target sample size: 258
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-003942-28
• 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: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Study Manager
• Affiliation: Takeda Development Centre Europe Ltd

• Name: Study Manager
• Affiliation: Takeda Development Centre Europe Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
2. The subject or, when applicable, the subject’s legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
3. The subject has chronic cholestatic liver disease, of at least 6 months duration, with a subsequent diagnosis of PSC, based on cholangiographic findings of intrahepatic and/or extrahepatic bile duct irregularities consistent with PSC.
4. The subject has a diagnosis of IBD (either UC, CD, or IBDU), established at least 3 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report.
5. The subject is male or female and aged 18 years and older, inclusive.
6. A male subject who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of the informed consent throughout the duration of the study and for 18 weeks after last dose.
7. A female subject of childbearing potential* who is sexually active with a non-sterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study and for 18 weeks after the last dose.
8. The subject has had a colorectal cancer screen within 12 months of the Screening Visit with no signs of malignancy, dysplasia, or neoplasia.
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 246
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion criteria:
1. The subject has had previous exposure to vedolizumab
2. The subject has a history of hypersensitivity or allergies to vedolizumab
3. The subject has had previous exposure to natalizumab, efalizumab, rituximab or any other integrin antagonist
4. The subject has received any investigational or approved biologic or biosimilar agent
5. The subject has received any of the following for the treatment of underlying disease within 30 days of screening:
• Nonbiologic therapies other than those specifically listed in the protocol Section 7.3.1 Permitted Medications for the Treatment of IBD
• An approved nonbiologic therapy in an investigational protocol
6. The subject has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes
7. The subject has any history of malignancy, except for (a) adequately treated nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has not recurred for at least 1 year prior to randomization; and (c) history of cervical carcinoma in situ that has not recurred for at least 3 years prior to randomization
8. The subject has a history of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demylelinating or neurodegenerative disease
9. The subject has a positive response on the PML subjective symptom checklist prior to the administration of study drug


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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Primary Sclerosing Cholangitis (PSC) Inflammatory Bowel Disease (IBD)
MedDRA version: 18.1 Level: LLT Classification code 10036732 Term: Primary sclerosing cholangitis System Organ Class: 100000004871
MedDRA version: 18.1 Level: PT Classification code 10021972 Term: Inflammatory bowel disease System Organ Class: 10017947 - Gastrointestinal disorders
MedDRA version: 18.1 Level: LLT Classification code 10021973 Term: Inflammatory bowel disease NOS System Organ Class: 10017947 - Gastrointestinal disorders

Intervention(s)

Trade Name: Entyvio
Product Name: Vedolizumab IV
Product Code: MLN0002
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Vedolizumab
CAS Number: 943609-66-3
Other descriptive name: VEDOLIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: To evaluate the effect of vedolizumab IV on inflammation and alkaline phosphatase (ALP) in non–end-stage PSC subjects with underlying IBD

Main Objective: To evaluate the efficacy and safety of vedolizumab IV in non–end-stage PSC subjects with underlying IBD

Primary end point(s): Proportion of subjects with no worsening in Ishak fibrosis staging score, from Baseline to the Week 106 visit

Timepoint(s) of evaluation of this end point: Week 106

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 106

Secondary end point(s): ? Proportion of subjects with a =35% reduction in serum ALP from Baseline to the Week 106 visit.
? Change in Ishak necroinflammatory grading score from the Baseline visit to the Week 106 visit.

Secondary ID(s)

2014-003942-28-ES

MLN0002-3023

Source(s) of Monetary Support

Takeda Development Centre Europe Ltd

Takeda Development Center Americas, Inc