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

Gilead Sciences

Status and phase: Terminated; Phase 2

Conditions: Primary Sclerosing Cholangitis

Treatments: Drug: Seladelpar; Drug: Placebo to match Seladelpar

Study type: Interventional

Funder types: Industry

Identifiers

NCT04024813

CB8025-21845

2019-001760-30 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1 participants in 4 patient groups, including a placebo group

Placebo (N=25)

Placebo Comparator group

Description:

Placebo for the remainder of the study

Treatment:

Drug: Placebo to match Seladelpar

Seladelpar 5 mg (N=25)

Experimental group

Description:

5 mg seladelpar daily for the remainder of the study

Treatment:

Drug: Seladelpar

Seladelpar 10 mg (N=25)

Experimental group

Description:

10 mg seladelpar for the remainder of the study

Treatment:

Drug: Seladelpar

Seladepar 25 mg (N=25)

Experimental group

Description:

25 mg seladelpar for the remainder of the study

Treatment:

Drug: Seladelpar