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

Phase 2

Terminated

• Conditions: Primary Sclerosing Cholangitis
• Interventions: Drug: Placebo to match Seladelpar; Drug: Seladelpar

• Registration Number: NCT04024813
• Lead Sponsor: Gilead Sciences

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-20
• Study First Submitted QC: 2019-07-16
• Study First Posted: 2019-07-18
• Study Start: 2019-11-12
• Primary Completion: 2020-01-09
• Study Completion: 2020-01-09
• Results First Submitted: 2024-12-09
• Status Verified: 2025-01
• Results First Submitted QC: 2025-01-15
• Last Update Submitted: 2025-01-15
• Results First Posted: 2025-01-16
• Last Update Posted: 2025-01-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

1. Confirmed diagnosis of primary sclerosing cholangitis (PSC) based on any two of the following three criteria:

   • Historical evidence of an elevated alkaline phosphatase (AP) > upper limit of normal (ULN) from any prior laboratory result
   • Liver biopsy consistent with PSC
   • Abnormal cholangiography consistent with PSC as measured by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or percutaneous transhepatic cholangiography (PTC)

2. Individuals 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
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN
   • Estimated glomerular filtration rate (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 ursodeoxycholic acid (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 immunoglobulin G4 (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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (N=25)	Placebo to match Seladelpar	Placebo for the remainder of the study
Seladelpar 5 mg (N=25)	Seladelpar	5 mg seladelpar daily for the remainder of the study
Seladelpar 10 mg (N=25)	Seladelpar	10 mg seladelpar for the remainder of the study
Seladepar 25 mg (N=25)	Seladelpar	25 mg seladelpar for the remainder of the study

Primary Outcome Measures

Name	Time	Method
Relative Change in Baseline Serum Alkaline Phosphatase (AP) at Week 24	Baseline, Week 24

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Up to Day 59	TEAEs were planned to be collected up to 24 weeks. Due to the early study termination, data is reported up to Day 59.
Incidence of Primary Sclerosing Cholangitis (PSC)-Related Symptoms or Procedures	Up to 24 weeks
Incidence of Hepatic Disease Progression Events	Up to 24 weeks	Hepatic disease progression events is defined by the first occurrence of the following events: liver transplantation, Model for End-Stage Liver Disease (MELD) score ≥ 15, hepatic decompensation events, and hepatocellular carcinoma.

Trial Locations

Locations (10)

University of Colorado Denver and Hospital; 🇺🇸 Aurora, Colorado, United States

Sutter Pacific Medical Foundation - California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Schiff Center for Liver Diseases/University of Miami; 🇺🇸 Miami, Florida, United States

Bon Secours Liver Institute of Richmond; 🇺🇸 Richmond, Virginia, United States

Liver Institute of Virginia; 🇺🇸 Newport News, Virginia, United States

New York University; 🇺🇸 New York, New York, United States

Toronto Centre for Liver Disease-Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

ID Clinic; 🇵🇱 Mysłowice, Poland

Piedmont Atlanta Hospital; 🇺🇸 Atlanta, Georgia, United States

Henry Ford Health System; 🇺🇸 Novi, Michigan, United States