Table 1 PRIMIS key inclusion and exclusion criteria

Men and nonpregnant, nonlactating women aged 18–75 years with diagnosis of large-duct PSC based on cholangiogram

Liver biopsy at screening deemed acceptable for interpretation and demonstrates stage F0–F3 fibrosis in opinion of central reader

 Historical liver biopsy within 6 months of screening visit may be accepted if deemed acceptable for interpretation

Individual has the following laboratory parameters at screening visit as determined by central laboratory:

 Platelet count ≥ 150,000/mm³

 eGFR ≥ 30 mL/min (per Cockcroft-Gault)

 ALT ≤ 8 × ULN

 Total bilirubin < 2 mg/dL unless individual has Gilbert's syndrome or hemolytic anemia

 INR ≤ 1.4 unless due to therapeutic anticoagulation

 Negative antimitochondrial antibody

For patients on UDCA, dose of UDCA must be stable for ≥ 6 months before screening; for those not on UDCA, no UDCA use for ≥ 6 months before screening

For patients on biologics, immunosuppressants, or systemic corticosteroids, dose must be stable for ≥ 3 months before screening and remain stable throughout trial

Current or prior history of any of following:

 Cirrhosis defined by stage F4 fibrosis according to Ludwig classification or equivalent on liver biopsy; decompensated liver disease including ascites, HE, and variceal hemorrhage; or liver stiffness > 20.0 kPa by FibroScan

 Liver transplantation

 Cholangiocarcinoma or HCC

 Ascending cholangitis within 30 days of screening

Presence of percutaneous drain or biliary stent

Other causes of liver disease

History of malignancy within 5 years of screening^a; unstable cardiovascular disease; hypercoagulable condition, or venous or arterial thromboembolic disease; or intestinal resection or malabsorptive condition

CP score > 6 unless due to alternate etiology

MELD score > 12 unless due to alternate etiology

HIV, HBV, or HCV infection

Current moderate–IBD, including ulcerative colitis, Crohn's disease, and indeterminate colitis