Table 2 Study endpoints

Primary endpoint

 Proportion of patients with liver fibrosis progression defined as ≥ 1-stage increase in fibrosis according to Ludwig classification at Week 96 (blinded phase)

Secondary endpoints (at Week 96 [blinded phase])

 Changes from baseline in serum concentrations of ALP, GGT, ALT, and bile acids

 Proportion of patients with ≥ 25% relative reduction in serum ALP concentration from baseline (biochemical response) and no worsening of fibrosis according to Ludwig classification (histologic response)

 Changes from baseline in liver fibrosis, including hepatic collagen content, fibrosis improvement, progression to cirrhosis (according to Ludwig classification), and noninvasive markers of fibrosis, including liver stiffness by FibroScan and ELF score

 Changes from baseline in HRQOL based on disease-specific PSC-PRO

Exploratory endpoints

 Changes from baseline in markers of liver injury and function, including bilirubin, albumin, and INR

 Changes in hepatitis and cholangitis activity, and bile duct loss (according to Nakanuma classification) at Week 96 (blinded phase)

 Changes from baseline in biliary stricture severity as measured by MRCP at Week 96 (blinded phase)

 Changes from baseline in HRQOL measures and health resource utilization

 Changes from baseline in Mayo risk score and Amsterdam-Oxford score

 Incidence of PSC-related complications including hepatic decompensation, ascending cholangitis, dominant strictures, cholangiocarcinoma, HCC, liver transplantation or meeting minimal listing criteria for transplantation (ie, MELD score ≥ 15), and mortality

 Event-free survival, defined as time to first clinical event. including histologic or clinical progression to cirrhosis, hepatic decompensation, liver transplantation, and all-cause mortality or last follow-up, whichever occurs first