Clinical trial NCT04480840: Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Lead sponsor: Pliant Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-07-21
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with treatment-related adverse events and laboratory abnormalities, as assessed by CTCAE v5.0
timeFrame: 12-48 weeks
Secondary outcomes:
measure: Assessment of PLN-74809 plasma concentrations
timeFrame: 12-48 weeks
Other outcomes:
measure: Changes from Baseline to Week 12 in liver fibrosis biomarkers and alkaline phosphatase (ALP) levels
timeFrame: 12-48 Weeks
Locations:
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Redwood City
country: United States
facility: Stanford University School of Medicine
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Lakewood Ranch
country: United States
facility: Florida Research Institute
state: Florida
city: Miami
country: United States
facility: Schiff Center of Liver Diseases/University of Miami
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital Gastroenterology Liver Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Digestive Disease Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine - Advanced Liver Therapies
state: Texas
city: Newport News
country: United States
facility: Bon Secours Liver Institute of Hampton Roads
state: Virginia
city: Richmond
country: United States
facility: VCU Health Clinical Research Services Unit
state: Virginia
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital: Department of Gastroenterology and Hepatology
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred
state: Victoria
city: Melbourne
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Graz
country: Austria
facility: Medizinische Universität Graz
city: Vienna
country: Austria
facility: Medical University of Vienna Div. of Gastroenterology and Hepatology
city: Bruxelles
country: Belgium
facility: Department Gastroenterology, Hepatopancreatology and Digestive Oncology CUB Hôpital Erasme
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
city: Calgary
country: Canada
facility: Aspen Woods Clinic
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital - Walter C. Mackenzie Health Sciences Centre
state: Alberta
city: Vancouver
country: Canada
facility: (G.I.R.I) GI Research Institute
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre-University Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Centre for Liver Disease (TCLD), University Health Network, Toronto General Hospital
state: Ontario
city: Montréal
country: Canada
facility: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Grenoble
country: France
facility: CHU Grenoble Alpes - Hôpital Michallon
city: Lille
country: France
facility: CHU de Lille service MAD
city: Paris
country: France
facility: Saint Antoine Hospital/ Hepatology Department
city: Strasbourg
country: France
facility: C.H.U. Hautepierre
city: Villejuif
country: France
facility: Centre Hépato-Biliaire - Hôpital Paul-Brousse
city: Berlin
country: Germany
facility: Charité University Medicine Berlin
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Hamburg
country: Germany
facility: University Medical Center Hamburg -Eppendorf/ I. Dept of Medicine
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz, I. Med. Klinik
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust
state: Norfolk
city: Headington
country: United Kingdom
facility: John Radcliffe Hospital/Oxford University Hospital
state: Oxford
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust, Denmark Hill
Study officials:
affiliation: Pliant Therapeutics, Inc.
name: Pliant Therapeutics Medical Monitor
role: STUDY_DIRECTOR
References: