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

NCT ID: NCT04480840

Last Updated: 2024-04-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

121 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-27

Study Completion Date

2024-03-18

Brief Summary

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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

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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

Conditions

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Primary Sclerosing Cholangitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

PLN-74809 Dose Level 1

Dose: 40 mg;

Group Type EXPERIMENTAL

PLN-74809

Intervention Type DRUG

PLN-74809

PLN-74809 Dose Level 2

Dose: 80 mg; PLN-74809 Dose Level 2 following PLN-74809 Dose Level 1

Group Type EXPERIMENTAL

PLN-74809

Intervention Type DRUG

PLN-74809

PLN-74809 Dose Level 3

Dose: 160 mg; PLN-74809 Dose Level 3 following PLN-74809 Dose Level 2

Group Type EXPERIMENTAL

PLN-74809

Intervention Type DRUG

PLN-74809

PLN-74809 Dose Level 4

Dose: 320 mg; PLN-74809 Dose Level 4 following PLN-74809 Dose Level 3

Group Type EXPERIMENTAL

PLN-74809

Intervention Type DRUG

PLN-74809

Interventions

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PLN-74809

PLN-74809

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pliant Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pliant Therapeutics Medical Monitor

Role: STUDY_DIRECTOR

Pliant Therapeutics, Inc.

Locations

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California Liver Research Institute

Pasadena, California, United States

Site Status

Stanford University School of Medicine

Redwood City, California, United States

Site Status

University of California, Davis Medical Center

Sacramento, California, United States

Site Status

California Pacific Medical Center Research Institute

San Francisco, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Yale School of Medicine

New Haven, Connecticut, United States

Site Status

Florida Research Institute

Lakewood Rch, Florida, United States

Site Status

Schiff Center of Liver Diseases/University of Miami

Miami, Florida, United States

Site Status

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Indiana University Health University Hospital

Indianapolis, Indiana, United States

Site Status

Massachusetts General Hospital Gastroenterology Liver Center

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Henry Ford Health System

Novi, Michigan, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt Digestive Disease Center

Nashville, Tennessee, United States

Site Status

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, United States

Site Status

Bon Secours Liver Institute of Hampton Roads

Newport News, Virginia, United States

Site Status

VCU Health Clinical Research Services Unit

Richmond, Virginia, United States

Site Status

Liver Institute Northwest

Seattle, Washington, United States

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

Liverpool Hospital: Department of Gastroenterology and Hepatology

Liverpool, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

The Alfred

Melbourne, Victoria, Australia

Site Status

St. Vincent's Hospital

Melbourne, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Medizinische Universität Graz

Graz, , Austria

Site Status

Medical University of Vienna Div. of Gastroenterology and Hepatology

Vienna, , Austria

Site Status

Department Gastroenterology, Hepatopancreatology and Digestive Oncology CUB Hôpital Erasme

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

Ghent University Hospital

Ghent, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Aspen Woods Clinic

Calgary, Alberta, Canada

Site Status

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

Edmonton, Alberta, Canada

Site Status

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

Vancouver, British Columbia, Canada

Site Status

McMaster University Medical Centre

Hamilton, Ontario, Canada

Site Status

London Health Sciences Centre-University Hospital

London, Ontario, Canada

Site Status

The Ottawa Hospital

Ottawa, Ontario, Canada

Site Status

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

Toronto, Ontario, Canada

Site Status

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

Montreal, Quebec, Canada

Site Status

McGill University Health Centre

Montreal, Quebec, Canada

Site Status

CHU Grenoble Alpes - Hôpital Michallon

Grenoble, , France

Site Status

CHU de Lille service MAD

Lille, , France

Site Status

Saint Antoine Hospital/ Hepatology Department

Paris, , France

Site Status

C.H.U. Hautepierre

Strasbourg, , France

Site Status

Centre Hépato-Biliaire - Hôpital Paul-Brousse

Villejuif, , France

Site Status

Charité University Medicine Berlin

Berlin, , Germany

Site Status

University Hospital Erlangen

Erlangen, , Germany

Site Status

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

Hamburg, , Germany

Site Status

University Hospital Heidelberg

Heidelberg, , Germany

Site Status

Universitätsmedizin Mainz, I. Med. Klinik

Mainz, , Germany

Site Status

Amsterdam UMC

Amsterdam, , Netherlands

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Erasmus University Medical Center

Rotterdam, , Netherlands

Site Status

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, Norfolk, United Kingdom

Site Status

John Radcliffe Hospital/Oxford University Hospital

Headington, Oxford, United Kingdom

Site Status

University Hospitals Birmingham NHS

Birmingham, , United Kingdom

Site Status

King's College Hospital NHS Foundation Trust, Denmark Hill

London, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada France Germany Netherlands United Kingdom

References

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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. 2025 Sep 26:S0168-8278(25)02498-5. doi: 10.1016/j.jhep.2025.09.016. Online ahead of print.

Reference Type DERIVED
PMID: 41016442 (View on PubMed)

Other Identifiers

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INTEGRIS-PSC

Identifier Type: OTHER

Identifier Source: secondary_id

PLN-74809-PSC-203

Identifier Type: -

Identifier Source: org_study_id

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