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

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)

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

Study Overview

• Status: Completed
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Placebo; Drug: PLN-74809

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

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital: Department of Gastroenterology and Hepatology
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred
    • Melbourne, Victoria, Australia, 3065
      • St. Vincent's Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Austria
  • Graz, Austria, 8036
    • Medizinische Universität Graz
  • Vienna, Austria, A-1090
    • Medical University of Vienna Div. of Gastroenterology and Hepatology
• Belgium
  • Brussels, Belgium, 1070
    • Department Gastroenterology, Hepatopancreatology and Digestive Oncology CUB Hôpital Erasme
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Ghent, Belgium, 9000
    • Ghent University Hospital
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3H 0V5
      • Aspen Woods Clinic
    • Edmonton, Alberta, Canada, T6G 2X8
      • University of Alberta Hospital - Walter C. Mackenzie Health Sciences Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • (G.I.R.I) GI Research Institute
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre-University Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto Centre for Liver Disease (TCLD), University Health Network, Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)
    • Montreal, Quebec, Canada, H4A3J1
      • McGill University Health Centre
• France
  • Grenoble, France, 38043 CEDEX 9
    • CHU Grenoble Alpes - Hopital Michallon
  • Lille, France, 59037
    • CHU de Lille service MAD
  • Paris, France, 75012
    • Saint Antoine Hospital/ Hepatology Department
  • Strasbourg, France, 67200
    • C.H.U. Hautepierre
  • Villejuif, France, 94800
    • Centre Hépato-Biliaire - Hôpital Paul-Brousse
• Germany
  • Berlin, Germany, 13353
    • Charité University Medicine Berlin
  • Erlangen, Germany, 91054
    • University Hospital Erlangen
  • Hamburg, Germany, 20246
    • University Medical Center Hamburg -Eppendorf/ I. Dept of Medicine
  • Heidelberg, Germany, 69120
    • University Hospital Heidelberg
  • Mainz, Germany, 55131
    • Universitätsmedizin Mainz, I. Med. Klinik
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus University Medical Center
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • University Hospitals Birmingham NHS
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust, Denmark Hill
  • Norfolk
    • Norwich, Norfolk, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospitals Nhs Foundation Trust
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 9DU
      • John Radcliffe Hospital/Oxford University Hospital
• United States
  • California
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Redwood City, California, United States, 94063
      • Stanford University School of Medicine
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • San Francisco, California, United States, 94109
      • California Pacific Medical Center Research Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale School of Medicine
  • Florida
    • Lakewood Rch, Florida, United States, 34211
      • Florida Research Institute
    • Miami, Florida, United States, 33136
      • Schiff Center of Liver Diseases/University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health University Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Gastroenterology Liver Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Perelman Center for Advanced Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Digestive Disease Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Advanced Liver Therapies
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Bon Secours Liver Institute of Hampton Roads
    • Richmond, Virginia, United States, 23298
      • VCU Health Clinical Research Services Unit
  • Washington
    • Seattle, Washington, United States, 98105
      • Liver Institute Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (Part 1, 2, and 3)	Drug: Placebo; Placebo
Experimental: PLN-74809 Dose Level 1; Part 1, Cohort 1 Dose: 40 mg, up to 12 weeks	Drug: PLN-74809; PLN-74809
Experimental: PLN-74809 Dose Level 2; Part 2, Cohort 2 Dose: 80 mg, up to 12 weeks; PLN-74809 Dose Level 2 following PLN-74809 Dose Level 1	Drug: PLN-74809; PLN-74809
Experimental: PLN-74809 Dose Level 3; Part 2, Cohort 3 Dose: 160 mg, up to 12 weeks; PLN-74809 Dose Level 3 following PLN-74809 Dose Level 1	Drug: PLN-74809; PLN-74809
Experimental: PLN-74809 Dose Level 4; Part 3, Cohort 4 Dose: 320 mg, for at least 24 weeks and up to 48 weeks; PLN-74809 Dose Level 4 following PLN-74809 Dose Levels 2 and 3	Drug: PLN-74809; PLN-74809

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events	Nature and proportion of TEAEs between PLN-74809 and placebo groups. Treatment-emergent adverse events (TEAEs) are defined as AEs that emerged or worsened in severity after the first administration of study drug	Up to 40 weeks
Number of Participants With Serious Treatment Emergent Adverse Events	Nature and proportion of Serious TEAEs between PLN-74809 and placebo groups. An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.	Up to 40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of PLN-74809 Total Plasma Concentrations at Week 12	Assessment of PLN-74809 Total Plasma Concentrations Week 12, 2 Hour Post Dose	Up to 12 weeks
Assessment of PLN-74809 Total Plasma Concentrations at Week 24	Assessment of PLN-74809 Total Plasma Concentrations Week 24, 2 Hour Post Dose	Up to 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Change From Baseline in Enhanced Liver Fibrosis (ELF) at Week 12	Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test derived from the measurement of hyaluronic acid (HA), amino terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloprotease 1 (TIMP1) using a proprietary algorithm (Siemens) which combines the 3 different tests that use 3 different units to produce a number that does not have a unit. ELF score is a laboratory test, is unitless, and is used as a continuous variable. The minimal ELF score is zero, the maximal ELF score is unknown. The higher the ELF score, the worse the disease outcome. ELF is a score of severity assessment against biopsy-proven fibrosis. A score of <7.7 is none to mild, >7.7-9.8 is moderate, >9.8 is severe.	Baseline to week 12
Assess Change From Baseline in Enhanced Liver Fibrosis (ELF) at Week 24	Enhanced Liver Fibrosis (ELF) score is a non-invasive blood test derived from the measurement of hyaluronic acid (HA), amino terminal propeptide of type III procollagen (PIIINP), and tissue inhibitor of metalloprotease 1 (TIMP1) using a proprietary algorithm (Siemens) which combines the 3 different tests that use 3 different units to produce a number that does not have a unit. ELF score is a laboratory test, is unitless, and is used as a continuous variable. The minimal ELF score is zero, the maximal ELF score is unknown. The higher the ELF score, the worse the disease outcome. ELF is a score of severity assessment against biopsy-proven fibrosis. A score of <7.7 is none to mild, >7.7-9.8 is moderate, >9.8 is severe.	Baseline to week 24
Assess Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12	Liver function Serum Alkaline Phosphatase (ALP) Change from Baseline to Week 12	Baseline to week 12
Assess Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 24	Liver function Serum Alkaline Phosphatase (ALP) Change from Baseline to Week 24	Baseline to week 24
Assess Percent Change From Baseline in PRO-C3 Liver Fibrosis Biomarker at Week 12	Assess change in PRO-C3 liver fibrosis biomarker from Baseline to Week 12	Baseline to week 12
Assess Percent Change From Baseline in PRO-C3 Liver Fibrosis Biomarker at Week 24	Assess change in PRO-C3 liver fibrosis biomarker from Baseline to Week 24	Baseline to week 24

Collaborators and Investigators

• Sponsor: Pliant Therapeutics, Inc.
• Investigators: Study Director: Pliant Therapeutics Medical Monitor, Pliant Therapeutics, Inc.

Publications and helpful links

General Publications

• Hirschfield GM, Kowdley KV, Trivedi PJ, Eksteen B, Hameed B, Vincent C, Chen T, Goel A, Reddy KG, Orman E, Joshi D, Lefebvre EA, Schaub JR, An MC, Clark A, Barnes CN, Pencek R, Thorburn D, Montano-Loza AJ, Schramm C, Bowlus CL, Trauner M, Levy C. Phase II INTEGRIS-PSC trial of bexotegrast, an alphavbeta6/alphavbeta1 integrin inhibitor, in primary sclerosing cholangitis. J Hepatol. 2026 Jan;84(1):86-98. doi: 10.1016/j.jhep.2025.09.016. Epub 2025 Sep 26.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2020
• Primary Completion (Actual): February 26, 2024
• Study Completion (Actual): March 18, 2024

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: PLN-74809-PSC-203; INTEGRIS-PSC (Other Identifier: Pliant Therapeutics Inc)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No