Efficacy and Safety of Vedolizumab Intravenous (IV) in the Treatment of Primary Sclerosing Cholangitis in Subjects With Underlying Inflammatory Bowel Disease

NCT03035058 | Withdrawn Phase 3 DMC

• 6 other identifiers: MLN0002-30232014-003942-28U1111-1161-490016/LO/0288NL56650.056.16191059
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Primary Sclerosing Cholangitis; Inflammatory Bowel Disease

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants with No Worsening in Ishak Fibrosis Staging Score from Baseline to Week 106 Visit

  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.

  Baseline and Week 106

Secondary Outcomes (2)

• 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

Study Arms (3)

Vedolizumab IV 300 mg Q4W

EXPERIMENTAL

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.

Drug: Vedolizumab

Vedolizumab IV 300 mg Q8W + Placebo

EXPERIMENTAL

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.

Drug: Vedolizumab; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Vedolizumab placebo-matching, IV, at Day 1 and Week 2; followed by Vedolizumab placebo-matching, IV, Q4W starting from Week 6 to Week 102.

Drug: Placebo

Interventions

Vedolizumab DRUG

Vedolizumab intravenous infusion

Also known as: MLN0002, ENTYVIO, KYNTELES

Vedolizumab IV 300 mg Q4W; Vedolizumab IV 300 mg Q8W + Placebo

Placebo DRUG

Placebo

Placebo; Vedolizumab IV 300 mg Q8W + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 0.24.
• 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.
• Has had 2 or more interventional treatments for dominant stricture (including stent placement/replacement) within 12 months prior to the Screening Visit.
• Has evidence of cholangitis, requiring antibiotics, within 3 months prior to the Screening Visit \[short courses of antibiotics for no more than 5 days are allowed for stent placement or endoscopic retrograde cholangiopancreatography (ERCP) prophylaxis\].
• Has chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Has positive hepatitis B core antibody (anti-HBc) at screening.
• Has evidence of an active infection during the Screening Period.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Cholangitis, Sclerosing; Inflammatory Bowel Diseases

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Gastroenteritis; Gastrointestinal Diseases; Intestinal Diseases

Study Officials

• Medical Director Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2017
• First Posted: January 27, 2017
• Study Start: February 1, 2017
• Primary Completion: September 1, 2020
• Study Completion: January 1, 2021
• Last Updated: March 8, 2017

Record last verified: 2017-03