Phase 2a Evaluation of Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Patients With Primary Sclerosing Cholangitis (PSC)
Purpose
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
Condition
- Primary Sclerosing Cholangitis
Eligibility
- Eligible Ages
- Between 18 Years and 75 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Placebo |
Placebo (Part 1, 2, and 3) |
|
|
Experimental PLN-74809 Dose Level 1 |
Part 1, Cohort 1 Dose: 40 mg, up to 12 weeks |
|
|
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 |
|
|
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 |
|
|
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 |
|
More Details
- Status
- Completed
- Sponsor
- Pliant Therapeutics, Inc.
Study Contact
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