A Study to Evaluate the Safety, and Tolerability, and Efficacy of Seladelpar in Patients With PSC

Study Overview
=================
Brief Summary
-----------------
The objectives of this study are to evaluate the effect of seladelpar treatment compared to placebo on efficacy, safety, and tolerability in patients with primary sclerosing cholangitis (PSC).

Official Title
-----------------
A Phase 2, Randomized, Double Blind, Placebo Controlled, Multiple Center Study to Evaluate the Safety, Tolerability, and Efficacy of Seladelpar Administered for 24 Weeks in Adult Patients With Primary Sclerosing Cholangitis (PSC)

Conditions
-----------------
Primary Sclerosing Cholangitis

Intervention / Treatment
-----------------
* Drug: Seladelpar
* Drug: Placebo to match Seladelpar


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Confirmed diagnosis of PSC based on any two of the following three criteria: Historical evidence of an elevated AP > ULN from any prior laboratory result Liver biopsy consistent with PSC Abnormal cholangiography consistent with PSC as measured by MRCP, ERCP, or percutaneous transhepatic cholangiography (PTC) Subjects must have the following specific additional laboratory parameters measured by the Central Laboratory at Screening: AP ≥ 1.5 × ULN and < 8 × ULN Total bilirubin ≤ 2 × ULN ALT and AST ≤ 5 × ULN eGFR > 60 mL/min/1.73 m^2 Platelets ≥ 140 × 10^3/µL International Normalized Ratio (INR) ≤ 1.3 (in the absence of warfarin or other anticoagulant therapy) Albumin ≥ 3.5 g/dL Patients taking UDCA will be allowed to enroll if meeting the following criteria: Total daily dose of ≤ 20 mg/kg/day A minimum of 6 months of stable treatment Minimum of 12 weeks off treatment prior to Screening if UDCA is recently discontinued Key Exclusion Criteria: Clinically significant acute or chronic liver disease of an etiology other than PSC Patients with a diagnosis of overlapping autoimmune hepatitis (AIH) and PSC Secondary or IgG4 related sclerosing cholangitis Small duct PSC Presence of a cholangiocarcinoma on cholangiography or MRI at Screening as determined by the central radiologist and the principal investigator (PI) or medical monitor Bile duct stent or percutaneous bile duct drain placement, or balloon dilatation procedure of a stricture within 12 weeks of Screening History, evidence, or high suspicion of cholangiocarcinoma or other hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms Presumptive or diagnosed acute cholangitis within 12 weeks of Screening and through Day 1 Evidence of compensated or decompensated cirrhosis based on histology, relevant medical complications, or laboratory parameters: Historical liver biopsy demonstrating cirrhosis (eg, Ludwig Stage 4 or Ishak Stage 5) Current or prior history of decompensated liver disease, including ascites, hepatic encephalopathy, variceal bleeding or other clinical conditions consistent with cirrhosis and/or portal hypertension, Liver stiffness > 14.4 kPa by FibroScan, or Combined low platelet count (< 140 × 10^3/µL ) with one of the following: Serum albumin < 3.5 g/dL, INR > 1.3 (not due to antithrombotic agent use), or Total bilirubin > ULN Prior or actively listed for liver transplantation Prior exposure to seladelpar Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo (N=25)<br>Placebo for the remainder of the study | Drug: Placebo to match Seladelpar<br>* Capsule(s) administered orally once daily<br>|
| Experimental: Seladelpar 5 mg (N=25)<br>5 mg seladelpar daily for the remainder of the study | Drug: Seladelpar<br>* Capsule(s) administered orally once daily<br>* Other names: MBX-8025;|
| Experimental: Seladelpar 10 mg (N=25)<br>10 mg seladelpar for the remainder of the study | Drug: Seladelpar<br>* Capsule(s) administered orally once daily<br>* Other names: MBX-8025;|
| Experimental: Seladepar 25 mg (N=25)<br>25 mg seladelpar for the remainder of the study | Drug: Seladelpar<br>* Capsule(s) administered orally once daily<br>* Other names: MBX-8025;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change in Baseline serum alkaline phosphatase (AP) at Week 24 |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs), as well as biochemistry, hematology, and urinalysis |  | Up to 24 weeks | 
| Incidence and severity of PSC-related symptoms or procedures |  | Up to 24 weeks | 
| Incidence of Hepatic disease progression events, defined by the occurrence of liver transplantation, MELD score, hepatic decompensation events, and/or hepatocellular carcinoma |  | Up to 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PSC, Cholangitis, Sclerosing, Cholangitis, Bile Duct Diseases, Biliary Tract Diseases, Digestive System Diseases