Development of Filociclovir for the Treatment of Ocular Adenoviral Infections and Keratoconjunctivitis

用于治疗眼部腺病毒感染和角结膜炎的非洛昔洛韦的开发

基本信息

  • 批准号:
    10410533
  • 负责人:
  • 金额:
    $ 71.28万
  • 依托单位:
  • 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:
    2021-06-01 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract The long-term goal of this project, to develop filociclovir (FCV) for the safe and effective treatment of human ocular adenovirus (AdV) infections, especially AdV-related epidemic keratoconjunctivitis (EKC), a stated National Eye Institute (NEI) research priority. There are currently no treatments for patients suffering from adenoviral conjunctivitis, which is responsible for up to 3.5 million lost school days and 8.5 million lost work days every year in the U.S., or EKC, the most severe form of ocular adenoviral infection, which often causes long-term visual sequelae, such as chronic keratitis and vision loss. As FCV has previously completed Phase 1 clinical studies for a systemic indication of cytomegalovirus (CMV) infection in solid organ transplant recipients and is a potent inhibitor of human adenoviruses, the objective of this SBIR proposal is to generate the remaining ocular-specific preclinical (PC) data needed to support an investigational new drug (IND) submission to treat human ocular AdV infections. In this Phase II SBIR, IND-enabling PC ocular pharmacokinetics (PK), biodistribution and GLP- toxicology studies will be completed, along with confirmatory efficacy parameters, suitable for IND submission. Additionally, we will confirm the mechanism of action of FCV against AdV and compare it with what is known for the viral targets in CMV. The specific aims of this proposal, along with the research design and methods, are as follows: AIM 1. Optimize eye drop formulation with suitable excipients and confirm efficacy in the rabbit AdV infection model (years 1-2). Milestones: Identify final formulation suitable for PC and human clinical ocular safety and efficacy studies. Select most favorable dose level, frequency and duration. Experimental design: formulation development, repeat Ad5/NZW rabbit eye infection model, dosage optimization in the same model. AIM 2. Perform IND-enabling ocular biodistribution, systemic toxicokinetics, local dose range finding ocular tolerance and repeat-dose ocular toxicology and supporting studies in albino rabbits and dogs (years 1-2). Milestones: Determine ocular and systemic exposure and distribution to predict areas of potential toxicity. Establish NOAEL to determine human clinical starting dose. Completion of acute local tolerance studies, GLP 28-day subacute ocular toxicology and in vitro phototoxicity studies to support an IND filing. Experimental design: complete remaining preclinical studies for the ocular route to support IND for ophthalmic product. AIM 3. Conduct mechanism of action studies (years 1-2). Milestones: Confirm viral and host polymerase and kinase targets. Experimental design: determine whether the mechanism of action identified for CMV is the same for AdV by performing mutation experiments.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Terry L. Bowlin其他文献

Investigating emN/em-arylpyrimidinamine (NAPA) compounds as early-stage inhibitors against human cytomegalovirus
调查 emN/em-芳基嘧啶胺(NAPA)化合物作为针对人类巨细胞病毒的早期抑制剂
  • DOI:
    10.1016/j.antiviral.2022.105474
  • 发表时间:
    2023-01-01
  • 期刊:
  • 影响因子:
    4.000
  • 作者:
    Andrea J. Parsons;Sabrina I. Ophir;Thomas J. Gardner;Jailene Casado Paredes;Kathryn R. Stein;Steven M. Kwasny;Steven C. Cardinale;Matthew Torhan;Mark N. Prichard;Scott H. James;Kristina E. Atanasoff;Narendran G-Dayanandan;Terry L. Bowlin;Timothy J. Opperman;Domenico Tortorella
  • 通讯作者:
    Domenico Tortorella
The immune response to a chemically induced fibrosarcoma
  • DOI:
    10.1007/bf00200197
  • 发表时间:
    1982-06-01
  • 期刊:
  • 影响因子:
    5.100
  • 作者:
    Terry L. Bowlin;Max R. Proffitt
  • 通讯作者:
    Max R. Proffitt
Adenosine A3 receptor agonists inhibit macrophage tumor necrosis factor‐α production
腺苷 A3 受体激动剂抑制巨噬细胞肿瘤坏死因子-α 的产生
  • DOI:
  • 发表时间:
    1996
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Terry L. Bowlin;David R. Borcherding;C. K. Edwards;C. McWhinney
  • 通讯作者:
    C. McWhinney
Inhibiteurs de la transformation de glycoprotéine ayant une activité antirétrovirale
糖蛋白转化抑制剂具有抗逆转录病毒活性
  • DOI:
  • 发表时间:
    1988
  • 期刊:
  • 影响因子:
    0
  • 作者:
    S. P. Sunkara;Terry L. Bowlin;Paul S. Liu
  • 通讯作者:
    Paul S. Liu
Methylacetylenic putrescine (MAP), an inhibitor of polyamine biosynthesis, prevents the development of collagen-induced arthritis.
甲基乙炔腐胺 (MAP) 是一种多胺生物合成抑制剂,可预防胶原诱导的关节炎的发生。
  • DOI:
    10.1016/0008-8749(90)90102-w
  • 发表时间:
    1990
  • 期刊:
  • 影响因子:
    4.3
  • 作者:
    J. Wolos;Deborah E. Logan;Terry L. Bowlin
  • 通讯作者:
    Terry L. Bowlin

Terry L. Bowlin的其他文献

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{{ truncateString('Terry L. Bowlin', 18)}}的其他基金

Development of Filociclovir for the Treatment of Ocular Adenoviral Infections and Keratoconjunctivitis
用于治疗眼部腺病毒感染和角结膜炎的非洛昔洛韦的开发
  • 批准号:
    10257718
  • 财政年份:
    2021
  • 资助金额:
    $ 71.28万
  • 项目类别:
Discovery of Zika virus therapeutics using a replicon assay
使用复制子测定发现寨卡病毒疗法
  • 批准号:
    9761977
  • 财政年份:
    2018
  • 资助金额:
    $ 71.28万
  • 项目类别:
Screening for rAAV transduction enhancers
筛选 rAAV 转导增强子
  • 批准号:
    10157565
  • 财政年份:
    2017
  • 资助金额:
    $ 71.28万
  • 项目类别:
Screening for rAAV transduction enhancers
筛选 rAAV 转导增强子
  • 批准号:
    10556347
  • 财政年份:
    2017
  • 资助金额:
    $ 71.28万
  • 项目类别:
Screening for rAAV transduction enhancers
筛选 rAAV 转导增强子
  • 批准号:
    9255016
  • 财政年份:
    2017
  • 资助金额:
    $ 71.28万
  • 项目类别:
Screening for rAAV transduction enhancers
筛选 rAAV 转导增强子
  • 批准号:
    10339432
  • 财政年份:
    2017
  • 资助金额:
    $ 71.28万
  • 项目类别:
Norovirus 3CL Protease-Based Anti-norovirus Therapeutics
基于诺如病毒 3CL 蛋白酶的抗诺如病毒疗法
  • 批准号:
    8615065
  • 财政年份:
    2014
  • 资助金额:
    $ 71.28万
  • 项目类别:
Novel Inhibitors Targeting Early Steps of Human Cytomegalovirus Replication
针对人类巨细胞病毒复制早期步骤的新型抑制剂
  • 批准号:
    8847279
  • 财政年份:
    2014
  • 资助金额:
    $ 71.28万
  • 项目类别:
Norovirus 3CL Protease-Based Anti-norovirus Therapeutics
基于诺如病毒 3CL 蛋白酶的抗诺如病毒疗法
  • 批准号:
    8793096
  • 财政年份:
    2014
  • 资助金额:
    $ 71.28万
  • 项目类别:
Evaluation of a new class of antimicrobial agents against Clostridium difficile
新型艰难梭菌抗菌药物的评价
  • 批准号:
    8337880
  • 财政年份:
    2011
  • 资助金额:
    $ 71.28万
  • 项目类别:

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