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)
Stanford University School of Medicine
🇺🇸Redwood City, California, United States
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital Gastroenterology Liver Center
🇺🇸Boston, Massachusetts, United States
Baylor College of Medicine - Advanced Liver Therapies
🇺🇸Houston, Texas, United States
Schiff Center of Liver Diseases/University of Miami
🇺🇸Miami, Florida, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
Florida Research Institute
🇺🇸Lakewood Ranch, Florida, United States
Piedmont Atlanta Hospital
🇺🇸Atlanta, Georgia, United States
Indiana University Health University Hospital
🇺🇸Indianapolis, Indiana, United States
Henry Ford Health System
🇺🇸Novi, Michigan, United States
Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Bon Secours Liver Institute of Hampton Roads
🇺🇸Newport News, Virginia, United States
VCU Health Clinical Research Services Unit
🇺🇸Richmond, Virginia, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Liver Institute Northwest
🇺🇸Seattle, Washington, United States
Liverpool Hospital: Department of Gastroenterology and Hepatology
🇦🇺Liverpool, New South Wales, Australia
The Alfred
🇦🇺Melbourne, Victoria, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
St. Vincent's Hospital
🇦🇺Melbourne, Victoria, Australia
Medical University of Vienna Div. of Gastroenterology and Hepatology
🇦🇹Vienna, Austria
Ghent University Hospital
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Aspen Woods Clinic
🇨🇦Calgary, Alberta, Canada
McMaster University Medical Centre
🇨🇦Hamilton, Ontario, Canada
London Health Sciences Centre-University Hospital
🇨🇦London, Ontario, Canada
Toronto Centre for Liver Disease (TCLD), University Health Network, Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
C.H.U. Hautepierre
🇫🇷Strasbourg, France
CHU Grenoble Alpes - Hôpital Michallon
🇫🇷Grenoble, France
Centre Hépato-Biliaire - Hôpital Paul-Brousse
🇫🇷Villejuif, France
Saint Antoine Hospital/ Hepatology Department
🇫🇷Paris, France
University Hospital Erlangen
🇩🇪Erlangen, Germany
Charité University Medicine Berlin
🇩🇪Berlin, Germany
University Medical Center Hamburg -Eppendorf/ I. Dept of Medicine
🇩🇪Hamburg, Germany
University Hospital Heidelberg
🇩🇪Heidelberg, Germany
Universitätsmedizin Mainz, I. Med. Klinik
🇩🇪Mainz, Germany
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Erasmus University Medical Center
🇳🇱Rotterdam, Netherlands
Norfolk and Norwich University Hospitals NHS Foundation Trust
🇬🇧Norwich, Norfolk, United Kingdom
John Radcliffe Hospital/Oxford University Hospital
🇬🇧Headington, Oxford, United Kingdom
King's College Hospital NHS Foundation Trust, Denmark Hill
🇬🇧London, United Kingdom
University Hospitals Birmingham NHS
🇬🇧Birmingham, United Kingdom
California Pacific Medical Center Research Institute
🇺🇸San Francisco, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Vanderbilt Digestive Disease Center
🇺🇸Nashville, Tennessee, United States
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Medizinische Universität Graz
🇦🇹Graz, Austria
Leiden University Medical Center
🇳🇱Leiden, Netherlands
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)
🇨🇦Montréal, Quebec, Canada
McGill University Health Centre
🇨🇦Montréal, Quebec, Canada
Department Gastroenterology, Hepatopancreatology and Digestive Oncology CUB Hôpital Erasme
🇧🇪Bruxelles, Belgium
University of Alberta Hospital - Walter C. Mackenzie Health Sciences Centre
🇨🇦Edmonton, Alberta, Canada
CHU de Lille service MAD
🇫🇷Lille, France
University of California, Davis Medical Center
🇺🇸Sacramento, California, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
(G.I.R.I) GI Research Institute
🇨🇦Vancouver, British Columbia, Canada