Primary Sclerosing Cholangitis
Conditions
Keywords
PSC, Cholangitis, Sclerosing, Cholangitis, Bile Duct Diseases, Biliary Tract Diseases, Digestive System Diseases
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).
Interventions
DRUGSeladelpar
Capsule(s) administered orally once daily
DRUGPlacebo to match Seladelpar
Capsule(s) administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Dose masking
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relative Change in Baseline Serum Alkaline Phosphatase (AP) at Week 24 | Baseline, Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada, Poland, United States
Participant flow
Recruitment details
Study was to be conducted in 60 sites in Australia, Europe, Israel, and North America. Only 1 site in the United States enrolled. The study was terminated early and only 1 participant was enrolled in the placebo arm.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participant received placebo once daily until Day 14. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study terminated by Sponsor | 1 |
Baseline characteristics
| Characteristic | Placebo | — |
|---|---|---|
| Age, Customized 65 to 84 years | 1 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 1 Participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Relative Change in Baseline Serum Alkaline Phosphatase (AP) at Week 24
Time frame: Baseline, Week 24
Population: The study was terminated before the outcome measure data were collected.
Secondary
Incidence of Hepatic Disease Progression Events
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.
Time frame: Up to 24 weeks
Population: The study was terminated before the outcome measure data were collected.
Secondary
Incidence of Primary Sclerosing Cholangitis (PSC)-Related Symptoms or Procedures
Time frame: Up to 24 weeks
Population: The study was terminated before the outcome measure data were collected.
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were planned to be collected up to 24 weeks. Due to the early study termination, data is reported up to Day 59.
Time frame: Up to Day 59
Population: The data for the participant that enrolled and received placebo was included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 0 Participants |