Background
biliary cirrhosis, cholestatic liver disease, fibrosis, cholestasis, PSC
BILIARY CIRRHOSIS, CHOLESTATIC LIVER DISEASE, FIBROSIS, CHOLESTASIS, PRIMARY SCLEROSING CHOLANGITIS, PERSISTENT INFLAMMATION
Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic liver disease of unknown etiology characterized by persistent inflammation, stricturing, and obliterative fibrosis of the bile ducts, ultimately resulting in biliary cirrhosis [The clinical management of PSC is challenging. While multiple drugs have been evaluated including immunosuppressants, antibiotics, and antifibrotics, no pharmacologic therapy has been proven to improve clinical outcomes [A key pathophysiologic feature of PSC is dysregulation of bile acid homeostasis, characterized by altered bile acid composition and cholestasis [Cilofexor (formerly GS-9674) is a potent and selective nonsteroidal FXR agonist [Based on the results from the phase 2 study, the efficacy and safety of cilofexor is now under evaluation in the PRIMIS trial (ClinicalTrials.gov NCT03890120, registered 26/03/2019). This manuscript describes the design and rationale for the largest, multinational, randomized, double-blind, placebo-controlled, phase 3 study in patients with PSC to date.