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

NCT04480840 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: PLN-74809-PSC-203INTEGRIS-PSC
• Study Type: interventional
• Target: 121
• Locations: 8 countries
• Sites: 58

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

Conditions

Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Assessment of PLN-74809 Total Plasma Concentrations at Week 12

  Up to 12 weeks

• Assessment of PLN-74809 Total Plasma Concentrations at Week 24

  Up to 24 weeks

Other Outcomes (6)

• Assess Change From Baseline in Enhanced Liver Fibrosis (ELF) at Week 12

  Baseline to week 12

• Assess Change From Baseline in Enhanced Liver Fibrosis (ELF) at Week 24

  Baseline to week 24

• Assess Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 12

  Baseline to week 12

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Placebo (Part 1, 2, and 3)

Drug: Placebo

PLN-74809 Dose Level 1

EXPERIMENTAL

Part 1, Cohort 1 Dose: 40 mg, up to 12 weeks

Drug: PLN-74809

PLN-74809 Dose Level 2

EXPERIMENTAL

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 Dose Level 3

EXPERIMENTAL

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 Dose Level 4

EXPERIMENTAL

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

Interventions

PLN-74809 DRUG

PLN-74809

PLN-74809 Dose Level 1; PLN-74809 Dose Level 2; PLN-74809 Dose Level 3; PLN-74809 Dose Level 4

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pliant Therapeutics, Inc.: lead

Study Sites (60)

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Stanford University School of Medicine

Redwood City, California, 94063, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

California Pacific Medical Center Research Institute

San Francisco, California, 94109, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06511, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211, United States

Location

Schiff Center of Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital Gastroenterology Liver Center

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Digestive Disease Center

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, 77030, United States

Location

Bon Secours Liver Institute of Hampton Roads

Newport News, Virginia, 23602, United States

Location

VCU Health Clinical Research Services Unit

Richmond, Virginia, 23298, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Liverpool Hospital: Department of Gastroenterology and Hepatology

Liverpool, New South Wales, 2170, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The Alfred

Melbourne, Victoria, 3004, Australia

Location

St. Vincent's Hospital

Melbourne, Victoria, 3065, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Medizinische Universität Graz

Graz, 8036, Austria

Location

Medical University of Vienna Div. of Gastroenterology and Hepatology

Vienna, A-1090, Austria

Location

Department Gastroenterology, Hepatopancreatology and Digestive Oncology CUB Hôpital Erasme

Brussels, 1070, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Ghent University Hospital

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Aspen Woods Clinic

Calgary, Alberta, T3H 0V5, Canada

Location

University of Alberta Hospital - Walter C. Mackenzie Health Sciences Centre

Edmonton, Alberta, T6G 2X8, Canada

Location

(G.I.R.I) GI Research Institute

Vancouver, British Columbia, V6Z 2K5, Canada

Location

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

London Health Sciences Centre-University Hospital

London, Ontario, N6A 5A5, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Toronto Centre for Liver Disease (TCLD), University Health Network, Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A3J1, Canada

Location

CHU Grenoble Alpes - Hôpital Michallon

Grenoble, 38043 CEDEX 9, France

Location

CHU de Lille service MAD

Lille, 59037, France

Location

Saint Antoine Hospital/ Hepatology Department

Paris, 75012, France

Location

C.H.U. Hautepierre

Strasbourg, 67200, France

Location

Centre Hépato-Biliaire - Hôpital Paul-Brousse

Villejuif, 94800, France

Location

Charité University Medicine Berlin

Berlin, 13353, Germany

Location

University Hospital Erlangen

Erlangen, 91054, Germany

Location

University Medical Center Hamburg -Eppendorf/ I. Dept of Medicine

Hamburg, 20246, Germany

Location

University Hospital Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsmedizin Mainz, I. Med. Klinik

Mainz, 55131, Germany

Location

Amsterdam UMC

Amsterdam, 1105 AZ, Netherlands

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Erasmus University Medical Center

Rotterdam, 3015 GD, Netherlands

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, Norfolk, NR4 7UY, United Kingdom

Location

John Radcliffe Hospital/Oxford University Hospital

Headington, Oxford, OX3 9DU, United Kingdom

Location

University Hospitals Birmingham NHS

Birmingham, B15 2GW, United Kingdom

Location

King's College Hospital NHS Foundation Trust, Denmark Hill

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41016442 DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Pliant Therapeutics Medical Monitor
• Organization: Pliant Therapeutics

clintrials@pliantrx.com

650-481-6770

Study Officials

• Pliant Therapeutics Medical Monitor

  Pliant Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2020
• First Posted: July 21, 2020
• Study Start: July 27, 2020
• Primary Completion: February 26, 2024
• Study Completion: March 18, 2024
• Last Updated: January 23, 2026
• Results First Posted: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (7); FR (5); GB (4); DE (5); NL (3); BE (4); US (21); CA (9)