Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC)

Primary Sclerosing Cholangitis Clinical Trial

Official title:

A Randomized, Double-blind, Dose-ranging, Placebo-controlled, Phase 2a Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Primary Sclerosing Cholangitis (PSC) and Suspected Liver Fibrosis (INTEGRIS-PSC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04480840
• Other study ID #: PLN-74809-PSC-203
• Secondary ID: INTEGRIS-PSC
• Status: Completed
• Phase: Phase 2
• Start date: July 27, 2020
• Est. completion date: March 18, 2024

Study information

• Verified date: August 2023
• Source: Pliant Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: March 18, 2024
• Est. primary completion date: February 26, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• PLN-74809
PLN-74809
• Placebo
Placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pliant Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes from Baseline to Week 12 in liver fibrosis biomarkers and alkaline phosphatase (ALP) levels	Absolute and relative changes from Baseline to Week 12 in liver fibrosis biomarkers (including PRO-C3 and ELF) and in ALP	12-48 Weeks
Primary	Number of participants with treatment-related adverse events and laboratory abnormalities, as assessed by CTCAE v5.0	Nature and proportion of AEs between PLN-74809 and placebo groups	12-48 weeks
Secondary	Assessment of PLN-74809 plasma concentrations	Plasma PLN-74809 concentrations (total and unbound concentrations) at each sampling timepoint	12-48 weeks