Clinical trial NCT04024813: A Study to Evaluate the Safety, and Tolerability, and Efficacy of Seladelpar in Patients With 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Keywords: PSC
Cholangitis, Sclerosing
Cholangitis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2019-07-18
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Relative Change in Baseline Serum Alkaline Phosphatase (AP) at Week 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Day 59
measure: Incidence of Primary Sclerosing Cholangitis (PSC)-Related Symptoms or Procedures
timeFrame: Up to 24 weeks
measure: Incidence of Hepatic Disease Progression Events
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Sutter Pacific Medical Foundation - California Pacific Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver and Hospital
state: Colorado
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: Atlanta
country: United States
facility: Piedmont Atlanta Hospital
state: Georgia
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: New York
country: United States
facility: New York University
state: New York
city: Newport News
country: United States
facility: Liver Institute of Virginia
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Liver Institute of Richmond
state: Virginia
city: Toronto
country: Canada
facility: Toronto Centre for Liver Disease-Toronto General Hospital
state: Ontario
city: Mysłowice
country: Poland
facility: ID Clinic
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: