Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC)
- Registration Number
- NCT04480840
- Lead Sponsor
- Pliant Therapeutics, Inc.
- Brief Summary
A Phase 2a, multicenter, randomized, double-blind, dose-ranging, placebo-controlled, study to evaluate the safety, tolerability, and PK of PLN-74809 in participants with primary sclerosing cholangitis and suspected liver fibrosis
- Detailed Description
Three-part study:
Part 1 - 12-week treatment period evaluating 40 mg of PLN-74809 or matching placebo \[Complete\] Part 2 - 12-week treatment period evaluating two dose groups, 80 mg and 160 mg of PLN-74809 or matching placebo Part 3 - minimum 24-week, up to 48-week treatment period evaluating 320 mg of PLN-74809 or matching placebo
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 121
- Established clinical diagnosis of large duct PSC based on an abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and/or percutaneous transhepatic cholangiopancreatography (PTC) in the context of cholestatic liver chemistry
- Suspected liver fibrosis, as defined by liver stiffness measurement (LSM), assessed by ultrasound-based transient elastography (TE, FibroScan®) OR Enhanced Liver Fibrosis (ELF) Score OR Historical liver biopsy showing fibrosis without cirrhosis (by any scoring system) OR Magnetic resonance elastography (MRE)
- Serum ALP concentration within normal limits or > 1 times the upper limit of normal (ULN)
- Participants receiving treatment for IBD are allowed, if on a stable dose from screening and expected to remain stable for the duration of the study
- Serum AST and ALT concentration ≤ 5 times the upper limit of normal
- If receiving treatment with UDCA, therapy is at a dose of < 25 mg/kg/day, has been stable for at least 3 months before screening.
- Other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically
- Known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis
- Small duct PSC with no evidence of large duct involvement (evidence of PSC on historical liver histology, with normal bile ducts on cholangiography)
- Presence of liver cirrhosis as assessed by liver histology, ultrasound-based liver stiffness measurement, ELF score, MRE, and/or signs and symptoms of hepatic decompensation (including but not limited to, jaundice, ascites, variceal hemorrhage, and/or hepatic encephalopathy.
- Serum ALP concentration > 10 times the upper limit of normal.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - PLN-74809 Dose Level 4 PLN-74809 Dose: 320 mg; PLN-74809 Dose Level 4 following PLN-74809 Dose Level 3 PLN-74809 Dose Level 1 PLN-74809 Dose: 40 mg; PLN-74809 Dose Level 3 PLN-74809 Dose: 160 mg; PLN-74809 Dose Level 3 following PLN-74809 Dose Level 2 PLN-74809 Dose Level 2 PLN-74809 Dose: 80 mg; PLN-74809 Dose Level 2 following PLN-74809 Dose Level 1
- Primary Outcome Measures
Name Time Method Number of participants with treatment-related adverse events and laboratory abnormalities, as assessed by CTCAE v5.0 12-48 weeks Nature and proportion of AEs between PLN-74809 and placebo groups
- Secondary Outcome Measures
Name Time Method Assessment of PLN-74809 plasma concentrations 12-48 weeks Plasma PLN-74809 concentrations (total and unbound concentrations) at each sampling timepoint
Trial Locations
- Locations (60)
California Liver Research Institute
🇺🇸Pasadena, California, United States
Stanford University School of Medicine
🇺🇸Redwood City, California, United States
University of California, Davis Medical Center
🇺🇸Sacramento, California, United States
California Pacific Medical Center Research Institute
🇺🇸San Francisco, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Florida Research Institute
🇺🇸Lakewood Ranch, Florida, United States
Schiff Center of Liver Diseases/University of Miami
🇺🇸Miami, Florida, United States
Piedmont Atlanta Hospital
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Scroll for more (50 remaining)California Liver Research Institute🇺🇸Pasadena, California, United States