Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary ducts in the liver resulting in destruction and fibrosis. PSC is associated with increased serum levels of hyaluronan (HA), an extracellular matrix polymer known to drive inflammation in multiple other tissues and disease models. Inhibition of HA synthesis with oral hymecromone has been shown to prevent progression of autoimmunity in several animal models. This is a prospective, open-label, single-center, pilot safety study of hymecromone in adults 18 years of age or older diagnosed with primary sclerosing cholangitis without evidence of hepatic fibrosis. Participants will be treated for 6 months with study drug. Safety and biomarkers of response will be monitored during therapy.