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

Primary Purpose

Primary Sclerosing Cholangitis

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PLN-74809
Placebo
Sponsored by
Pliant Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 > 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 (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.

Sites / Locations

  • California Liver Research Institute
  • Stanford University School of Medicine
  • University of California, Davis Medical Center
  • California Pacific Medical Center Research Institute
  • University of California San Francisco
  • Yale School of Medicine
  • Florida Research Institute
  • Schiff Center of Liver Diseases/University of Miami
  • Piedmont Atlanta Hospital
  • University of Chicago Medical Center
  • Indiana University Health University Hospital
  • Massachusetts General Hospital Gastroenterology Liver Center
  • University of Michigan
  • Henry Ford Health System
  • Duke University Medical Center
  • Perelman Center for Advanced Medicine
  • Vanderbilt Digestive Disease Center
  • Baylor College of Medicine - Advanced Liver Therapies
  • Bon Secours Liver Institute of Hampton Roads
  • VCU Health Clinical Research Services Unit
  • Liver Institute Northwest
  • Royal Prince Alfred Hospital
  • Liverpool Hospital: Department of Gastroenterology and Hepatology
  • Westmead Hospital
  • Royal Adelaide Hospital
  • The Alfred
  • St. Vincent's Hospital
  • Sir Charles Gairdner Hospital
  • Medizinische Universität Graz
  • Medical University of Vienna Div. of Gastroenterology and Hepatology
  • Department Gastroenterology, Hepatopancreatology and Digestive Oncology CUB Hôpital Erasme
  • Universitair Ziekenhuis Antwerpen
  • Ghent University Hospital
  • UZ Leuven
  • Aspen Woods Clinic
  • University of Alberta Hospital - Walter C. Mackenzie Health Sciences Centre
  • (G.I.R.I) GI Research Institute
  • McMaster University Medical Centre
  • London Health Sciences Centre-University Hospital
  • The Ottawa Hospital
  • Toronto Centre for Liver Disease (TCLD), University Health Network, Toronto General Hospital
  • Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)
  • McGill University Health Centre
  • CHU Grenoble Alpes - Hôpital Michallon
  • CHU de Lille service MAD
  • Saint Antoine Hospital/ Hepatology Department
  • C.H.U. Hautepierre
  • Centre Hépato-Biliaire - Hôpital Paul-Brousse
  • Charité University Medicine Berlin
  • University Hospital Erlangen
  • University Medical Center Hamburg -Eppendorf/ I. Dept of Medicine
  • University Hospital Heidelberg
  • Universitätsmedizin Mainz, I. Med. Klinik
  • Amsterdam UMC
  • Leiden University Medical Center
  • Erasmus University Medical Center
  • Norfolk and Norwich University Hospitals NHS Foundation Trust
  • John Radcliffe Hospital/Oxford University Hospital
  • University Hospitals Birmingham NHS
  • King's College Hospital NHS Foundation Trust, Denmark Hill

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo

PLN-74809 Dose Level 1

PLN-74809 Dose Level 2

PLN-74809 Dose Level 3

PLN-74809 Dose Level 4

Arm Description

Dose: 40 mg;

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Assessment of PLN-74809 plasma concentrations
Plasma PLN-74809 concentrations (total and unbound concentrations) at each sampling timepoint

Full Information

First Posted
July 13, 2020
Last Updated
October 17, 2023
Sponsor
Pliant Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04480840
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 27, 2020 (Actual)
Primary Completion Date
February 29, 2024 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pliant Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
112 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
PLN-74809 Dose Level 1
Arm Type
Experimental
Arm Description
Dose: 40 mg;
Arm Title
PLN-74809 Dose Level 2
Arm Type
Experimental
Arm Description
Dose: 80 mg; PLN-74809 Dose Level 2 following PLN-74809 Dose Level 1
Arm Title
PLN-74809 Dose Level 3
Arm Type
Experimental
Arm Description
Dose: 160 mg; PLN-74809 Dose Level 3 following PLN-74809 Dose Level 2
Arm Title
PLN-74809 Dose Level 4
Arm Type
Experimental
Arm Description
Dose: 320 mg; PLN-74809 Dose Level 4 following PLN-74809 Dose Level 3
Intervention Type
Drug
Intervention Name(s)
PLN-74809
Intervention Description
PLN-74809
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events and laboratory abnormalities, as assessed by CTCAE v5.0
Description
Nature and proportion of AEs between PLN-74809 and placebo groups
Time Frame
12-48 weeks
Secondary Outcome Measure Information:
Title
Assessment of PLN-74809 plasma concentrations
Description
Plasma PLN-74809 concentrations (total and unbound concentrations) at each sampling timepoint
Time Frame
12-48 weeks
Other Pre-specified Outcome Measures:
Title
Changes from Baseline to Week 12 in liver fibrosis biomarkers and alkaline phosphatase (ALP) levels
Description
Absolute and relative changes from Baseline to Week 12 in liver fibrosis biomarkers (including PRO-C3 and ELF) and in ALP
Time Frame
12-48 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pliant Therapeutics Medical Monitor
Organizational Affiliation
Pliant Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
California Liver Research Institute
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
Stanford University School of Medicine
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
California Pacific Medical Center Research Institute
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Yale School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Florida Research Institute
City
Lakewood Ranch
State/Province
Florida
ZIP/Postal Code
34211
Country
United States
Facility Name
Schiff Center of Liver Diseases/University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Piedmont Atlanta Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University Health University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Massachusetts General Hospital Gastroenterology Liver Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Henry Ford Health System
City
Novi
State/Province
Michigan
ZIP/Postal Code
48377
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Perelman Center for Advanced Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt Digestive Disease Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Baylor College of Medicine - Advanced Liver Therapies
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Bon Secours Liver Institute of Hampton Roads
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
VCU Health Clinical Research Services Unit
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Liver Institute Northwest
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Liverpool Hospital: Department of Gastroenterology and Hepatology
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
The Alfred
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
St. Vincent's Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Medizinische Universität Graz
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Medical University of Vienna Div. of Gastroenterology and Hepatology
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Department Gastroenterology, Hepatopancreatology and Digestive Oncology CUB Hôpital Erasme
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Ghent University Hospital
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Aspen Woods Clinic
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3H 0V5
Country
Canada
Facility Name
University of Alberta Hospital - Walter C. Mackenzie Health Sciences Centre
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2X8
Country
Canada
Facility Name
(G.I.R.I) GI Research Institute
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z 2K5
Country
Canada
Facility Name
McMaster University Medical Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
London Health Sciences Centre-University Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Toronto Centre for Liver Disease (TCLD), University Health Network, Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X 0A9
Country
Canada
Facility Name
McGill University Health Centre
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4A3J1
Country
Canada
Facility Name
CHU Grenoble Alpes - Hôpital Michallon
City
Grenoble
ZIP/Postal Code
38043 CEDEX 9
Country
France
Facility Name
CHU de Lille service MAD
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Saint Antoine Hospital/ Hepatology Department
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
C.H.U. Hautepierre
City
Strasbourg
ZIP/Postal Code
67200
Country
France
Facility Name
Centre Hépato-Biliaire - Hôpital Paul-Brousse
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Charité University Medicine Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
University Hospital Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
University Medical Center Hamburg -Eppendorf/ I. Dept of Medicine
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
University Hospital Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Universitätsmedizin Mainz, I. Med. Klinik
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Amsterdam UMC
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Erasmus University Medical Center
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands
Facility Name
Norfolk and Norwich University Hospitals NHS Foundation Trust
City
Norwich
State/Province
Norfolk
ZIP/Postal Code
NR4 7UY
Country
United Kingdom
Facility Name
John Radcliffe Hospital/Oxford University Hospital
City
Headington
State/Province
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Facility Name
University Hospitals Birmingham NHS
City
Birmingham
ZIP/Postal Code
B15 2GW
Country
United Kingdom
Facility Name
King's College Hospital NHS Foundation Trust, Denmark Hill
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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