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IND-Enabling Studies for Arenavirus Preclinical Candidate

沙粒病毒临床前候选药物的 IND 启用研究

基本信息

批准号：
10216086
负责人：
Gregory William Henkel
金额：
$ 130.8万
依托单位：
ARISAN THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-13 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10216086
关键词：
Adopted Africa Anemia Antiviral Agents Arenavirus Autopsy Autoradiography Back Bile fluid Canis familiaris Cardiac Category A pathogen Cells Clinical Clinical Research Development Dimethyl Sulfoxide Disease Dose Drops Drug or chemical Tissue Distribution Embryo Engineering Equilibrium Excretory function Exhibits Eye Family Feces Female Formulation Future Genes Geography Glycoproteins Goals Healthcare Systems Hemorrhage Hepatocyte Human In Vitro Incubated Industry Infection Ingestion Inhalation Label Lassa Fever Lassa virus Liquid substance Modeling Morbidity - disease rate Mutation Nose Old World Arenaviruses Oral Oryctolagus cuniculus Pain Pathogenicity Patients Pharmaceutical Preparations Pharmacology Phase Phenotype Placebo Control Plasma Property Radio Rattus Respiratory distress Ribavirin Risk Risk Assessment Rodent Safety Sampling Shock South America Survivors Swelling Symptoms Therapeutic Thrombocytopenia Time Tissues Toxic effect Transplantation Treatment Efficacy Urine Vero Cells Viral Viral Hemorrhagic Fevers Virus Diseases Vomiting Western Africa Zoonoses animal efficacy cohort enzyme activity flu healthy volunteer in vivo infected vector rodent inhibitor/antagonist intravenous administration mRNA Expression mortality nanomolar patch clamp pathogen pill pre-clinical pregnant product development prophylactic reproductive toxicity scale up side effect transmission process viral resistance virology weapons

项目摘要

Summary Arenaviruses comprise a diverse family. Several species are associated with severe arenaviral hemorrhagic fever (AVHF) in humans. Human infection with arenaviruses typically occurs through contact with materials contaminated with the excretions of an infected rodent although direct human- to-human transmission may occur in clinical settings. AVHF resulting from infection with the Old World arenavirus Lassa is estimated to cause over 300,000 annual infections in Western Africa, of which 15-20% of hospitalized patients die while survivors often suffer permanent sequelae. The intravenous administration of the nonspecific antiviral agent has been adopted ribavirin (off-label) for Lassa virus infections in Western Africa. However, it has been shown to provide limited efficacy and a significant risk for serious side effects including thrombocytopenia and anemia. Given the limited treatment and prophylactic options, the mortality/morbidity rate, the potential for both zoonotic and human-to-human transmission, geographical transplantation and bio-weaponization six arenaviruses have been recognized as Category A pathogens. In order to provide a potent and specific antiviral to treat Lassa and other arenavirus hemorrhagic fevers here we propose the completion of IND-enabling studies and advanced nonclinical studies for an oral preclinical candidate entry inhibitor with sub-nanomolar broad spectrum arenavirus activity and demonstrable drug-like features that exhibits remarkable in vivo therapeutic efficacy.

总结沙粒病毒包括一个不同的家庭。几个物种与严重的人类的沙粒病毒出血热（AVHF）。人感染沙粒病毒典型地通过与被动物排泄物污染的材料接触而发生虽然在临床环境中可能发生人与人之间的直接传播，据估计，由旧大陆沙粒病毒拉沙感染引起的AVHF可导致西非每年有30多万例感染，其中15-20%的住院患者死亡，而幸存者往往遭受永久性后遗症。静脉内施用非特异性抗病毒剂利巴韦林（标签外）已被用于拉沙病毒感染，西非。然而，它已被证明提供有限的疗效和显著的风险，严重的副作用包括血小板减少和贫血。考虑到有限的治疗和预防选择，死亡率/发病率，潜在的人畜共患病和人传人、地域移植和生物武器化六种沙粒病毒被认为是A类病原体。为了提供有效和特异性的抗病毒治疗拉沙和其他沙粒病毒出血热在这里，我们建议完成IND使能性研究和高级非临床研究，具有亚纳摩尔广谱沙粒病毒活性的临床前候选进入抑制剂，具有可证明的药物样特征，其表现出显著的体内治疗功效。