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NCT Number: NCT04480840

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

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Key information

Conditions

Primary Sclerosing Cholangitis Bile Duct Diseases Biliary Tract Diseases Cholangitis Cholangitis, Sclerosing Digestive System Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

Loading trial locations.

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PLN-74809

Drug

PLN-74809

Placebo

Drug

Placebo

Primary outcomes

  1. Number of Participants With Treatment Emergent Adverse Events

    Time frame: Up to 40 weeks

    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

  2. Number of Participants With Serious Treatment Emergent Adverse Events

    Time frame: Up to 40 weeks

    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.

Secondary outcomes

  1. Assessment of PLN-74809 Total Plasma Concentrations at Week 12

    Time frame: Up to 12 weeks

    Assessment of PLN-74809 Total Plasma Concentrations Week 12, 2 Hour Post Dose

  2. Assessment of PLN-74809 Total Plasma Concentrations at Week 24

    Time frame: Up to 24 weeks

    Assessment of PLN-74809 Total Plasma Concentrations Week 24, 2 Hour Post Dose

Other outcomes

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

    Time frame: Baseline to 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.

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

    Time frame: Baseline to 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.

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

    Time frame: Baseline to week 12

    Liver function Serum Alkaline Phosphatase (ALP) Change from Baseline to Week 12

  4. Assess Change From Baseline in Serum Alkaline Phosphatase (ALP) at Week 24

    Time frame: Baseline to week 24

    Liver function Serum Alkaline Phosphatase (ALP) Change from Baseline to Week 24

  5. Assess Percent Change From Baseline in PRO-C3 Liver Fibrosis Biomarker at Week 12

    Time frame: Baseline to week 12

    Assess change in PRO-C3 liver fibrosis biomarker from Baseline to Week 12

  6. Assess Percent Change From Baseline in PRO-C3 Liver Fibrosis Biomarker at Week 24

    Time frame: Baseline to week 24

    Assess change in PRO-C3 liver fibrosis biomarker from Baseline to Week 24

Sponsors and collaborators

Lead sponsor

Pliant Therapeutics, Inc.

Industry

Registry information

Official study 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)

Important dates

Study start
2020
Primary completion
2024
Study completion
2024
First posted
Jul 21, 2020
Registry last updated
Jan 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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