Pilot Trial UO1 DUR-928

急性酒精性肝病是一种急性酒精性肝病，包括从轻微损伤到严重损伤的范围， 有生命危险的伤害。急性肝炎的患病率还没有得到准确的确定；据信有10%的人会发生这种情况 对35%的酗酒者来说。在组织学上，急性胰腺炎的特点是炎症细胞和 肝细胞损伤。持续饮酒通常与进行性纤维化有关。 虐待。自从皮质类固醇作为一种治疗急性肝炎的药物引入以来，还没有成功的新药被开发出来。 20世纪70年代初的治疗。皮质类固醇已被用作各种治疗的标准护理。 严重急性胰腺炎患者指南。己酮可可碱也因其安全性而被使用，但有几个 良好的研究尚未支持己酮可可碱治疗重症急性肝炎的疗效。 重要的是，最近的一项研究质疑了泼尼松和己酮可可碱在治疗高血压病中的疗效。 阿。服用泼尼松、己酮可可碱或两者同时服用的患者6个月的死亡率与 安慰剂。因此，需要新的治疗方法。DUR-928是一种内源性细胞内调节剂 分子和硫酸氧固醇：5-胆固酮-3-β，25-二醇-3-硫酸酯(25HC3S)。DUR-928正在开发中 用于多种适应症，包括治疗慢性代谢性疾病，如NAFLD/NASH和PSC，以及 急性器官损伤的治疗，如AKI和AH。DUR-928可降低细胞内脂质 蓄积，调节炎症反应，提高细胞存活率。根据目前积累的 通过对DUR-928生物学知识的了解，我们认为DUR-928代表了一种治疗急性肝炎的新药物 极佳的安全性(内源性生产)。在这个试点UO1中，我们建议2个独立的，但关联的 学习。 研究1：一项开放标签的剂量递增研究，以评估DUR的安全性、药代动力学和疗效。 928例中度酒精性肝炎患者。 研究2：一项开放标签的剂量递增研究，以评估DUR的安全性、药代动力学和疗效。 928例重型酒精性肝炎患者。

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.