A Non-Inferiority Randomized Single Blind Controlled Trial Comparing One and Two Dose Regimes of Oxfendazole versus a Two Dose Regime of Triclabendazole to Treat Chronic Fascioliasis

比较奥芬达唑一剂和两剂方案与三氯苯达唑两剂方案治疗慢性片形吸虫病的非劣效随机单盲对照试验

• 批准号: 10328194
• 负责人: MIGUEL MAURICIO CABADA
• 金额: $ 43.91万
• 依托单位: UNIVERSIDAD PERUANA CAYETANO HEREDIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10328194
• 关键词: Address; Adult; Affect; Animals; Anthelmintics; Antiparasitic Agents; Area; Biological Availability; Case Study; Child; Chile; Chronic; Clinical Trials; Communities; Conduct Clinical Trials; Controlled Clinical Trials; Country; Cysticercosis; Data; Developing Countries; Development; Dose; Drug Exposure; Drug Kinetics; Enrollment; Ensure; Environment; Epidemiology; Evaluation; Exposure to; Fasciola; Fasciola hepatica; Fascioliasis; Formulation; Helminths; Human; Infection; Literature; Liver diseases; Livestock; Logistics; Measures; Meleagris gallopavo; Methods; Modeling; Nature; Netherlands; Oral; Parasites; Parasitic infection; Parasitology; Persons; Peru; Pharmaceutical Preparations; Phase; Population; Portugal; Principal Investigator; Procedures; Published Comment; Randomized; Regimen; Reporting; Research; Research Personnel; Resistance; Safety; Sheep; Single-Blind Study; Solid; Taenia solium; Tissues; Toxicology; Treatment Protocols; Variant; Work; Zoonoses; arm; benzimidazole; climate change; comparative efficacy; design; drug development; effective therapy; efficacy evaluation; experience; farmer; helminth infection; human tissue; multidisciplinary; novel therapeutics; pharmacokinetic model; phase 1 study; programs; randomized, clinical trials; standard of care; trial comparing

Oxfendazole in Fascioliasis Principal Investigators/Program Directors: GARCIA, Hector H./ CABADA, Miguel M. A Non-Inferiority Randomized Single Blind Controlled Trial Comparing One and Two Dose Regimes of Oxfendazole versus a Two Dose Regime of Triclabendazole to Treat Chronic Fascioliasis ABSTRACT Fasciola hepatica infection causes human liver disease in wide endemic regions around the world. Triclabendazole is the only effective drug to treat human fascioliasis. However, it is not widely available and recently reports about resistance in livestock and decreased efficacy in humans raise concerns for the availability of effective treatment in human infections. Triclabendazole (TCBZ) resistance in human has been reported in The Netherlands, Turkey, Chile, Portugal, and Peru. In our experience in Cusco, Peru, more than 40% of children treated with one triclabendazole dose failed to achieve parasitological cure and 60% of these failed a second dose of treatment. Oxfendazole (OXF) is a veterinary benzimidazole with a wide anti-helminthic spectrum. Our group has demonstrated that OXF is highly efficacious against Taenia solium cysticercosis and other helminths. A preliminary study in naturally infected sheep showed that OXF is also highly efficacious against Fasciola hepatica. We have completed animal toxicology and phase 1 OXF studies in humans, confirming the high bioavailability of OXF and, importantly, its safety. These data strongly suggest that OXF is an excellent candidate for the treatment of human fascioliasis. Therefore, we propose to compare two oral OXF treatment regimens, a single 20 mg/kg dose and two 20 mg/kg doses, against the standard of care of two 10 mg/kg oral doses of TCBZ for the treatment of 336 children and adults with chronic Fasciola hepatica infection in endemic areas of Cusco, Peru. In addition, population PK modeling will be performed among subjects randomized to the OXF arms. This study will evaluate the efficacy, safety, and population pharmacokinetics of OXF in the groups most affected by fascioliasis. This application builds upon our 25-years of experience working with OXF and takes advantage of the solid expertise of the PIs in helminth infections, prior pivotal randomized clinical trials of anti- parasitic treatment in cysticercosis, and our continued work in a well-known Fasciola-endemic region in the Andes Mountains of Cusco. The investigators supported by the Oxfendazole Development Group will form a multidisciplinary team of accomplished experts in fascioliasis, field epidemiology, clinical trials, and new drug development that will ensure the successful completion of this study. This trial has the potential to provide a new standard of care for the treatment of chronic fascioliasis. In addition, it will be the first evaluation of OXF efficacy for a human tissue parasite and constitutes a significant step forward towards making this promising drug available for the treatment of human. It will provide additional pharmacokinetic and safety data to advance OXF development as a human drug.

羊肉症中的施芬唑首席研究人员/计划董事：加西亚，赫克托·H·卡卡达（Hector H.）/卡巴达（Cabada） 比较一个和 两种剂量的牛津唑与两个剂量的制度 三苯甲唑治疗慢性筋膜病 抽象的 fasciola Hepatica感染在世界各地广泛的地方性地区引起人类肝病。 Triclabendazole是唯一治疗人类筋膜病的有效药物。但是，它不是广泛的 最近报道了有关牲畜抵抗和人类疗效降低引起的关注的报道 为了获得人类感染的有效治疗。 Triclabendazole（TCBZ）抗性 人类已在荷兰，土耳其，智利，葡萄牙和秘鲁有报道。根据我们的经验 秘鲁的库斯科（Cusco），超过40％的用三苯甲唑剂量治疗的儿童未能实现 寄生虫治愈和其中60％的治疗失败了第二剂剂量的治疗。 牛丹唑（OXF）是一种兽医苯咪唑，具有广泛的抗固定光谱。我们的小组 已经证明OXF对Taenia silium囊肿和其他 蠕虫。在自然感染绵羊的初步研究表明，OXF也是高效的 反对Fasciola Hepatica。我们已经完成了人类的动物毒理学和第1阶段的OXF研究， 确认了OXF的高生物利用度，重要的是它的安全性。这些数据强烈表明 OXF是治疗人筋膜病的绝佳候选者。因此，我们建议 比较两种口服oxf治疗方案，一个20 mg/kg剂量和两个20 mg/kg剂量 两种10 mg/kg口服TCBZ的护理标准用于治疗336名儿童和成人 秘鲁库斯科州流行地区的慢性筋膜肝病感染。此外，人口PK 建模将在随机分配给OXF臂的受试者之间进行。这项研究将评估 OXF的疗效，安全性和人口药代动力学在最受筋膜症影响的组中。 该应用程序建立在我们与OXF合作的25年经验的基础上，并利用 PI在蠕虫感染中的稳固专业知识，先前的抗抗临床试验 囊性的寄生虫治疗，以及我们在著名筋膜地区的继续工作 在库斯科的安第斯山脉。牛津唑发展支持的调查人员 小组将组成一个多学科的团队，由筋膜病，现场流行病学专家组成， 临床试验和新药物开发将确保成功完成这项研究。这 试验有可能为治疗慢性筋膜病的治疗提供新的护理标准。在 此外，这将是对人体组织寄生虫oxf功效的首次评估，并构成A 朝着使这种有前途的药物可用于治疗人类的重要一步。会 提供其他药代动力学和安全性数据，以推动OXF开发作为人类药物。