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
Overview
- Phase
- Phase 3
- Status
- Withdrawn
- Sponsor
- Takeda
- Primary Endpoint
- Percentage of Participants with No Worsening in Ishak Fibrosis Staging Score from Baseline to Week 106 Visit
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •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.
- •Has a liver stiffness transient elastography (TE) score of ≤14.3 kPa, as assessed by FibroScan.
- •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
- •Has received any fibrates within 8 weeks of Screening.
- •Has high suspicion of cholangiocarcinoma, as indicated by an elevated Ca 19-9 value (\>129 U/mL) at screening.
- •Has evidence of overlap syndrome with autoimmune hepatitis or primary or secondary biliary cirrhosis or autoimmune cholangitis, as judged by the investigator.
- •Has evidence of alcoholic liver disease including history of alcoholic hepatitis.
- •Has a diagnosis of small duct PSC.
- •Has a Model for End-Stage Liver Disease (MELD) score \>12 at screening.
- •Has a Child-Pugh score \>7 (following adjustment for PSC diagnosis) at screening.
- •Has received a liver transplant.
- •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.
Arms & Interventions
Vedolizumab IV 300 mg Q4W
Vedolizumab 300 mg, intravenous (IV), once at Day 1 and Week 2; followed by vedolizumab 300 mg, IV, once every 4 weeks (Q4W) starting from Week 6 to Week 102.
Intervention: Vedolizumab (Drug)
Vedolizumab IV 300 mg Q8W + Placebo
Vedolizumab 300 mg, IV, once at Day 1 and Week 2; followed by vedolizumab 300 mg, IV, once every 8 weeks (Q8W) starting from Week 6 to Week 102 (and placebo, IV, Q8W starting from Week 10 to Week 98.
Intervention: Vedolizumab (Drug)
Vedolizumab IV 300 mg Q8W + Placebo
Vedolizumab 300 mg, IV, once at Day 1 and Week 2; followed by vedolizumab 300 mg, IV, once every 8 weeks (Q8W) starting from Week 6 to Week 102 (and placebo, IV, Q8W starting from Week 10 to Week 98.
Intervention: Placebo (Drug)
Placebo
Vedolizumab placebo-matching, IV, at Day 1 and Week 2; followed by Vedolizumab placebo-matching, IV, Q4W starting from Week 6 to Week 102.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percentage of Participants with No Worsening in Ishak Fibrosis Staging Score from Baseline to Week 106 Visit
Time Frame: 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 Outcomes
- Percentage of Participants with a ≥35% Reduction in Serum Alkaline Phosphatase (ALP) from Baseline to Week 106 Visit(Baseline and Week 106)
- Change in Ishak Necroinflammatory Grading Score from Baseline to the Week 106 Visit(Baseline and Week 106)