What side effects are associated with this type of intervention?

Common treatments for Primary Sclerosing Cholangitis (PSC) include glucocorticoids, thiopurines, ursodeoxycholic acid (UDCA), and vancomycin. Glucocorticoids can cause side effects such as weight gain, hypertension, and increased risk of infections. Thiopurines may lead to bone marrow suppression, liver toxicity, and increased risk of infections. UDCA is generally well-tolerated but can cause diarrhea and, at higher doses, may be detrimental. Vancomycin, used in some pediatric cases, can cause nephrotoxicity and ototoxicity. These treatments aim to manage symptoms and complications but do not alter the disease's natural progression.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically for Primary Sclerosing Cholangitis (PSC). Current management strategies often involve off-label use of medications such as ursodeoxycholic acid (UDCA) to improve liver function tests, although its efficacy in altering disease progression is uncertain. Other treatments under investigation include immunosuppressive and anti-inflammatory agents, such as those being studied in trials like PLN-74809. Liver transplantation remains the definitive treatment for advanced PSC.

What other types of research exist?

Promising novel alternatives to PLN-74809 for Primary Sclerosing Cholangitis patients include: 1) RO5459072, a cathepsin S inhibitor, which has shown pharmacodynamic efficacy in clinical studies. 2) BRD5529, a CARD9 inhibitor, which has demonstrated effectiveness in preclinical models of inflammatory signaling. 3) Chol-DsiRNA polyplexes targeting STAT3, which have shown increased potency and therapeutic activity in preclinical breast cancer models and could be explored for liver diseases.

← Back to Search

Unknown

PLN-74809 for Sclerosing Cholangitis

Phase 2

Waitlist Available

Research Sponsored by Pliant Therapeutics, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12-48 weeks

Awards & highlights

Study Summary

This trial is studying a potential new treatment for primary sclerosing cholangitis and liver fibrosis. It is assessing the safety and tolerability of the drug as well as how it is processed by the body.

Who is the study for?

This trial is for people with a condition called primary sclerosing cholangitis (PSC), which affects the liver's bile ducts. Participants should have abnormal liver tests or suspected liver fibrosis, but not advanced cirrhosis. They can be on stable IBD treatment and must not have other causes of liver disease like autoimmune hepatitis or viral infections.Check my eligibility

What is being tested?

The study is testing PLN-74809, a potential new medication for PSC, against a placebo (a substance with no active drug). It's designed to see how safe it is and how the body processes it. People will be randomly assigned to receive either PLN-74809 or placebo without knowing which one they're getting.See study design

What are the potential side effects?

While specific side effects are not listed here, common ones in trials like this may include gastrointestinal symptoms, headaches, fatigue, and possible allergic reactions. The safety profile of PLN-74809 will be closely monitored throughout the study.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with large duct PSC based on specific liver tests.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12-48 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12-48 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12-48 weeks for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Number of participants with treatment-related adverse events and laboratory abnormalities, as assessed by CTCAE v5.0

Secondary outcome measures

Assessment of PLN-74809 plasma concentrations

Other outcome measures

Changes from Baseline to Week 12 in liver fibrosis biomarkers and alkaline phosphatase (ALP) levels

Trial Design

5Treatment groups

Experimental Treatment

Placebo Group

Group I: PLN-74809 Dose Level 4Experimental Treatment1 Intervention

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

Group II: PLN-74809 Dose Level 3Experimental Treatment1 Intervention

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

Group III: PLN-74809 Dose Level 2Experimental Treatment1 Intervention

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

Group IV: PLN-74809 Dose Level 1Experimental Treatment1 Intervention

Dose: 40 mg;

Group V: PlaceboPlacebo Group1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

PLN-74809

2020

Completed Phase 2

~260

0 / 1Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Primary Sclerosing Cholangitis (PSC) include ursodeoxycholic acid (UDCA), glucocorticoids, thiopurines, and vancomycin. UDCA works by reducing bile acid toxicity and improving bile flow, which can help alleviate cholestasis and liver inflammation. Glucocorticoids and thiopurines are immunosuppressive agents that reduce inflammation and immune-mediated damage to the bile ducts. Vancomycin, an antibiotic, has shown some promise in small studies, potentially by altering gut microbiota and reducing bacterial translocation that may contribute to PSC. These treatments are crucial for PSC patients as they aim to manage symptoms, slow disease progression, and improve quality of life. While the specific mechanism of PLN-74809 is not detailed, it is likely being investigated for its potential to target similar pathways involved in fibrosis and inflammation, which are central to PSC pathology.

New Therapeutic Targets in Autoimmune Cholangiopathies.β-Adrenoceptor blockade in sclerosing cholangitis of Mdr2 knockout mice: antifibrotic effects in a model of nonsinusoidal fibrosis.