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.

奥芬达唑治疗肝片吸虫病主要研究人员/项目主任：加西亚，赫克托·H/卡巴达，米格尔·M。 一项非劣势随机单盲对照试验 奥芬达唑的两种剂量方案与两种剂量方案的比较 三氯苯咪唑治疗慢性肝片吸虫病 摘要 肝片吸虫感染在世界各地广泛流行的地区导致人类肝病。 三氯苯达唑是治疗人类肝片吸虫病的唯一有效药物。然而，它并不是广泛可用的 最近关于家畜抗药性和人类药效下降的报道引起了人们的关注。 为人类感染提供有效的治疗方法。三氯苯达唑(TCBZ)耐药性的研究 据报道，荷兰、土耳其、智利、葡萄牙和秘鲁都有人感染病例。在我们的经验中 秘鲁库斯科，超过40%的儿童接受一剂三氯苯达唑治疗后未能达到 寄生虫学治愈，其中60%的人第二次治疗失败。 奥芬达唑(Oxfendazol，Oxf)是一种具有广谱抗蠕虫活性的兽用苯并咪唑类药物。我们的团队 已证明Oxf对猪带绦虫囊虫病和其他 蠕虫。对自然感染的绵羊的初步研究表明，Oxf也是非常有效的 抗肝片吸虫。我们已经完成了动物毒理学和人类OXF第一阶段研究， 证实了Oxf的高生物利用度，更重要的是，它的安全性。这些数据有力地表明， OXF是治疗人类肝片吸虫病的极佳候选药物。因此，我们建议 比较两种口服氧氟沙星治疗方案，一次20 mg/kg剂量和两次20 mg/kg剂量，对 两种10 mg/kg口服TCBZ治疗336例儿童和成人的护理标准 秘鲁库斯科流行区慢性肝片吸虫感染。另外，人口主键 建模将在随机分配到Oxf手臂的受试者中进行。这项研究将评估 在受肝片吸虫病影响最严重的人群中，Oxf的有效性、安全性和群体药代动力学。 这个应用程序建立在我们25年的Oxf工作经验的基础上，并利用 PIs在蠕虫感染方面的扎实专业知识，先前关键的抗-HBs随机临床试验 囊虫病的寄生虫治疗，以及我们在著名的片吸虫流行区的持续工作 在库斯科的安第斯山脉。奥芬达唑研发支持下的研究人员 该小组将组建一支由肝片吸虫病、现场流行病学、 临床试验和新药开发将确保这项研究的成功完成。这 试验有可能为慢性肝片吸虫病的治疗提供一种新的护理标准。在……里面 此外，这将是首次评估Oxf对人体组织寄生虫的疗效，并构成 朝着使这种有希望的药物用于治疗人类疾病迈出了重要的一步。会的 提供更多的药代动力学和安全性数据，以促进Oxf作为人类药物的开发。