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

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)

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).

Study Overview

• Status: Completed
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Placebo to match Seladelpar; Drug: Seladelpar

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto Centre for Liver Disease-Toronto General Hospital
• Poland
  • Mysłowice, Poland, 41-400
    • ID Clinic
• United States
  • California
    • San Francisco, California, United States, 94109
      • Sutter Pacific Medical Foundation - California Pacific Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver and Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • Schiff Center for liver Diseases/University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
  • New York
    • New York, New York, United States, 10016
      • New York University
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Liver Institute of Virginia
    • Richmond, Virginia, United States, 23226
      • Bon Secours Liver Institute of Richmond

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. 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)

2. 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

3. 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:

1. Clinically significant acute or chronic liver disease of an etiology other than PSC
2. Patients with a diagnosis of overlapping autoimmune hepatitis (AIH) and PSC
3. Secondary or IgG4 related sclerosing cholangitis
4. Small duct PSC
5. Presence of a cholangiocarcinoma on cholangiography or MRI at Screening as determined by the central radiologist and the principal investigator (PI) or medical monitor
6. Bile duct stent or percutaneous bile duct drain placement, or balloon dilatation procedure of a stricture within 12 weeks of Screening
7. History, evidence, or high suspicion of cholangiocarcinoma or other hepatobiliary malignancy based on imaging, screening laboratory values, and/or clinical symptoms
8. Presumptive or diagnosed acute cholangitis within 12 weeks of Screening and through Day 1

9. 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
10. Prior or actively listed for liver transplantation
11. Prior exposure to seladelpar

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo (N=25); Placebo for the remainder of the study	Drug: Placebo to match Seladelpar; Capsule(s) administered orally once daily
EXPERIMENTAL: Seladelpar 5 mg (N=25); 5 mg seladelpar daily for the remainder of the study	Drug: Seladelpar; Capsule(s) administered orally once daily; Other Names: MBX-8025
EXPERIMENTAL: Seladelpar 10 mg (N=25); 10 mg seladelpar for the remainder of the study	Drug: Seladelpar; Capsule(s) administered orally once daily; Other Names: MBX-8025
EXPERIMENTAL: Seladepar 25 mg (N=25); 25 mg seladelpar for the remainder of the study	Drug: Seladelpar; Capsule(s) administered orally once daily; Other Names: MBX-8025

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: CymaBay Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 12, 2019
• Primary Completion (ACTUAL): January 9, 2020
• Study Completion (ACTUAL): January 9, 2020

Study Registration Dates

• First Submitted: June 20, 2019
• First Submitted That Met QC Criteria: July 16, 2019
• First Posted (ACTUAL): July 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 3, 2021
• Last Update Submitted That Met QC Criteria: June 1, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Digestive System Diseases; PSC; Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Cholangitis, Sclerosing
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Seladelpar
• Other Study ID Numbers: CB8025-21845; 2019-001760-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No