Pilot Trial UO1 DUR-928

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AH is an acute form of alcoholic liver disease and includes a spectrum that ranges from mild injury to severe, life threatening injury. The prevalence of AH has not been accurately determined; it is believed to occur in 10% to 35% of heavy drinkers. On histology, AH is characterized by infiltration of the liver by inflammatory cells and hepatocellular injury. AH is usually associated with progressive fibrosis in the presence of continued alcohol abuse. No new drugs for AH have been successfully developed since the introduction of corticosteroids as a treatment in the early 1970s. Corticosteroids have been utilized as a standard of care in various treatment guidelines for patients with severe AH. Pentoxifylline has also been used because of its safety, but several well-conducted studies have not supported the efficacy of pentoxifylline for the treatment of severe AH. Importantly, a recent study has questioned the efficacy of both prednisone and pentoxifylline in the treatment of AH. Mortality at 6 months was similar in patients on either prednisone, pentoxifylline, or both as compared with placebo. Therefore, there is a need for novel therapies. DUR-928 is an endogenous intracellular regulatory molecule and sulfated oxysterol: 5-cholesten-3β, 25-diol 3-sulfate (25HC3S). DUR-928 is under development for multiple indications including treatment of chronic metabolic disease, such as NAFLD/NASH and PSC, and treatment of acute organ injuries, such as AKI and AH. DUR-928 is able to lower intracellular lipid accumulation, regulate inflammatory responses, and improve cell survival. Based on the current accumulated knowledge of DUR-928 biology, we believe that DUR-928 represents a novel therapeutic agent for AH with an excellent safety profile (is produced endogenously). In this PILOT UO1, we propose 2 independent, but linked studies. Study #1: An open-label, dose escalation study to assess the safety, pharmacokinetics and efficacy of DUR- 928 in patients with Moderate Alcoholic Hepatitis. Study #2: An open-label, dose escalation study to assess the safety, pharmacokinetics and efficacy of DUR- 928 in patients with Severe Alcoholic Hepatitis.