Inflammatory Bowel Disease, Primary Sclerosing Cholangitis
Conditions
Keywords
Drug therapy
Brief summary
The purpose of this study is to evaluate the efficacy and safety of vedolizumab intravenous (IV) in non-end-stage primary sclerosing cholangitis (PSC) participants with underlying inflammatory bowel disease (IBD).
Detailed description
The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have non-end-stage primary sclerosing cholangitis (PSC) with underlying inflammatory bowel disease (IBD). This study will look at changes in fibrosis staging in people who take vedolizumab. The study will enroll approximately 258 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the three treatment groups in ratio 1:1:1-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): * Vedolizumab 300 mg once every 4 weeks (Q4W) * Vedolizumab 300 mg once every 8 weeks (Q8W) * Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient All participants will be administered vedolizumab or placebo via intravenous infusion This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 124 weeks. Participants will make multiple visits to the clinic and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.
Interventions
DRUGVedolizumab
Vedolizumab intravenous infusion
DRUGPlacebo
Placebo
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with No Worsening in Ishak Fibrosis Staging Score from Baseline to Week 106 Visit | Baseline and Week 106 | Assessments will be performed from liver biopsies with histology assessed by 2 independent blinded central readers for Ishak fibrosis staging score. Ishak fibrosis staging scoring is as follows: 0=No fibrosis, 1=Fibrous expansion of some portal areas with or without septa, 2=Fibrous expansion of most portal areas with or without septa, 3=Fibrous expansion of most portal areas with occasional portal to portal bridging, 4=Fibrous expansion of portal areas with marked bridging (portal to portal and/or portal to central), 5=Marked bridging with occasional nodules (incomplete cirrhosis), 6=Cirrhosis, probable or definitive. A negative change from Baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with a ≥35% Reduction in Serum Alkaline Phosphatase (ALP) from Baseline to Week 106 Visit | Baseline and Week 106 | Blood will be collected and ALP will be assessed as part of the serum chemistry testing. |
| Change in Ishak Necroinflammatory Grading Score from Baseline to the Week 106 Visit | Baseline and Week 106 | Assessments will be performed from liver biopsies with histology assessed by 2 independent blinded central readers for Ishak fibrosis staging score. Ishak necroinflammatory grading score is based on assessments from 4 subscales: (A) Periportal or periseptal interface hepatitis (piecemeal necrosis) 5-point subscale (0=Absent to 4=Severe), (B) Confluent necrosis 7-point subscale (0=Absent to 6=Panacinar or multiacinar necrosis), (C) Focal (spotty) lytic necrosis, apoptosis and focal inflammation 5-point subscale (0=Absent to 4=More than ten foci per times 10 objective), and (D) Portal inflammation (0=Absent to 4=Marked, all portal areas). A negative change from Baseline indicates improvement. |
Outcome results
None listed