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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 16 December 2017
Main ID:  NCT03035058
Date of registration: 25/01/2017
Prospective Registration: Yes
Primary sponsor: Takeda
Public title: Efficacy and Safety of Vedolizumab Intravenous (IV) in the Treatment of Primary Sclerosing Cholangitis in Subjects With Underlying Inflammatory Bowel Disease
Scientific title: A 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: February 2017
Target sample size: 0
Recruitment status: Withdrawn
URL:  https://clinicaltrials.gov/show/NCT03035058
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).  
Phase:  Phase 3
Countries of recruitment
Contacts
Name:     Medical Director Clinical Science
Address: 
Telephone:
Email:
Affiliation:  Takeda
Key inclusion & exclusion criteria

Inclusion Criteria:

1. Has chronic cholestatic liver disease, of at least 6 months duration, with a
subsequent diagnosis of primary sclerosing cholangitis (PSC), based on
cholangiographic findings of intrahepatic and/or extrahepatic bile duct irregularities
consistent with PSC.

2. Has a diagnosis of inflammatory bowel disease (IBD) (either ulcerative colitis [UC],
Crohn's disease [CD], or IBD unclassified [IBDU]), established at least 3 months prior
to enrollment by clinical and endoscopic evidence and corroborated by a histopathology
report.

3. Has a liver stiffness transient elastography (TE) score of =14.3 kPa, as assessed by
FibroScan.

4. Has had a colorectal cancer screen within 12 months of the Screening Visit with no
signs of malignancy, dysplasia, or neoplasia.

Exclusion Criteria:

Hepatic and Gastrointestinal Exclusion Criteria

1. Has received any fibrates within 8 weeks of Screening.

2. Has high suspicion of cholangiocarcinoma, as indicated by an elevated Ca 19-9 value
(>129 U/mL) at screening.

3. Has evidence of overlap syndrome with autoimmune hepatitis or primary or secondary
biliary cirrhosis or autoimmune cholangitis, as judged by the investigator.

4. Has evidence of alcoholic liver disease including history of alcoholic hepatitis.

5. Has a diagnosis of small duct PSC.

6. Has a Model for End-Stage Liver Disease (MELD) score >12 at screening.

7. Has a Child-Pugh score >7 (following adjustment for PSC diagnosis) at screening.

8. Has received a liver transplant.

9. Has evidence of autoimmune immunoglobin (Ig) IgG4-associated cholangitis, as defined
by elevated serum IgG4 at least 2 x ULN (at screening), or IgG4/IgG1 ratio above 0.24.

10. Has undergone prior biliary surgery (laparoscopic or open surgery). Participants who
have undergone cholecystectomy without surgical complications will be allowed provided
the surgery was not done within 6 weeks prior to screening.

11. Has had 2 or more interventional treatments for dominant stricture (including stent
placement/replacement) within 12 months prior to the Screening Visit.

12. Has evidence of cholangitis, requiring antibiotics, within 3 months prior to the
Screening Visit [short courses of antibiotics for no more than 5 days are allowed for
stent placement or endoscopic retrograde cholangiopancreatography (ERCP) prophylaxis].

Infectious Disease Exclusion Criteria

13. Has chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

14. Has positive hepatitis B core antibody (anti-HBc) at screening.

15. Has evidence of an active infection during the Screening Period.

16. Has any identified congenital or acquired immunodeficiency (eg, common variable
immunodeficiency, human immunodeficiency virus [HIV] infection, organ
transplantation).

17. Has active or latent tuberculosis (TB), regardless of treatment history, as evidenced
by any of the following:

1. History of TB.

2. A positive diagnostic TB test within 30 days of enrollment defined as: 1. A
positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests (or, a
positive T-SPOT TB test [Japan only]), OR

3. Chest X-ray within 3 months of enrollment in which active or latent pulmonary TB
cannot be excluded

General Exclusion Criteria

18. Has had previous exposure to natalizumab, efalizumab, rituximab, or any other integrin
antagonist.

19. Has received any of the following for the treatment of underlying disease within 30
days of screening:

- Nonbiologic therapies (eg, cyclosporine, tacrolimus, thalidomide) other than
those specifically listed in the protocol for the treatment of IBD.

- An approved nonbiologic therapy in an investigational protocol.

20. Has, in the judgment of the investigator, clinically significant abnormal
hematological parameters of hemoglobin, hematocrit, or erythrocytes at the Screening
Visit.

21. Has any history of malignancy, except for the following: (a) adequately treated
nonmetastatic basal cell skin cancer; (b) squamous cell skin cancer that has been
adequately treated and that has not recurred for at least 1 year prior to
randomization; and (c) history of cervical carcinoma in situ that has been adequately
treated and that has not recurred for at least 3 years prior to randomization.
Participant with remote history of malignancy (eg, >10 years since completion of
curative therapy without recurrence) will be considered based on the nature of the
malignancy and the therapy received and must be discussed with the sponsor on a
case-by-case basis prior to randomization.

22. Has a history of any major neurological disorders, including stroke, multiple
sclerosis, brain tumor, demyelinating or neurodegenerative disease.

23. Has a positive response on the progressive multifocal leukoencephalopathy (PML)
subjective symptom checklist prior to the administration of study drug.

24. Has received any of the following for the treatment of underlying disease within 30
days of screening:

- Nonbiologic therapies (eg, cyclosporine, tacrolimus, thalidomide) other than
those specifically listed in the protocol for the treatment of IBD.

- An approved nonbiologic therapy in an investigational protocol.

25. Has had any surgical procedure requiring general anesthesia within 30 days prior to
screening or is planning to undergo major surgery during the study.

26. Is required to take excluded medications.

27. Has received any live vaccinations within 30 days prior to screening.

28. Has evidence of or treatment for C. difficile infection within 60 days or other
intestinal pathogen within 30 days prior to the Screening Visit or other known
infectious, immunologic, or ischemic liver or intestinal disease that, in the
investigator's opinion, may interfere with the study procedures or study results.

29. Has, in the judgment of the investigator, clinically significant abnormal
hematological parameters of hemoglobin, hematocrit, or erythrocytes at the Screening
Visit.

30. Has previous history of colectomy.

31. In the opinion of the investigator, the participant has a life expectancy or
anticipated need for liver transplantation within <24 months.

32. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol
abuse within 1 year prior to screening.

33. For the magnetic resona



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
Inflammatory Bowel Disease
Primary Sclerosing Cholangitis
Intervention(s)
Drug: Placebo
Drug: Vedolizumab
Primary Outcome(s)
Percentage of Participants with No Worsening in Ishak Fibrosis Staging Score from Baseline to Week 106 Visit [Time Frame: Baseline and Week 106]
Secondary Outcome(s)
Change in Ishak Necroinflammatory Grading Score from Baseline to the Week 106 Visit [Time Frame: Baseline and Week 106]
Percentage of Participants with a =35% Reduction in Serum Alkaline Phosphatase (ALP) from Baseline to Week 106 Visit [Time Frame: Baseline and Week 106]
Secondary ID(s)
16/LO/0288
191059
2014-003942-28
MLN0002-3023
NL56650.056.16
U1111-1161-4900
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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