Griffithsin-based Rectal Microbicides for PREvention of Viral ENTry (PREVENT)

基于 Griffithsin 的直肠杀菌剂用于预防病毒进入（预防）

基本信息

批准号：
8769373
负责人：
KENNETH E PALMER
金额：
$ 363.9万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8769373
关键词：
Address Affect Animals Antiviral Agents Anus Cells Characteristics Chemistry Clinical Clinical Protocols Clinical Research Clinical Trials Colorectal Confidentiality Critical Pathways Cyclic GMP Data Data Set Development Documentation Dosage Forms Dose Drug Delivery Systems Drug Formulations Drug Kinetics Ensure Epidemic Epithelium Feedback Future Gel Goals Guidelines HIV HIV-1 Hepatitis C virus Human Human Herpesvirus 2 Immune response Immunoassay Immunohistochemistry Institution Investigational Drugs Investigational New Drug Application Laboratories Lead Lectin Licensure Local Microbicides Lubricants Macaca mulatta Manufacturer Name Marines Measures Methodology Methods Modeling Mucous Membrane Nucleosides Participant Peptides Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Phase I Clinical Trials Placebo Control Placebos Population Practice Management Pre-Clinical Model Preclinical Testing Prevention Process Prophylactic treatment Proteins Proteomics Randomized Recombinants Recovery Recruitment Activity Regulation Research Reverse Transcriptase Inhibitors Risk Safety Sampling Services Staging System TMC120-R147681 Techniques Technology Transfer Tenofovir Topical application Toxicology Trauma United States Food and Drug Administration United States National Institutes of Health Universities Ursidae Family Vagina Viral Virus Work analytical method antiretroviral therapy base clinical efficacy condoms design efficacy testing expectation immunotoxicity inhibitor/antagonist innovation irritation manufacturing process medical schools meetings microbicide microbiome next generation non-nucleoside reverse transcriptase inhibitors novel pre-clinical preclinical efficacy preclinical safety preclinical study prevent product development programs prototype public health relevance rectal rectal microbicide safety study safety testing small molecule superinfection transcriptomics transmission process viral resistance volunteer

项目摘要

DESCRIPTION (provided by applicant): PREVENT (Pre-exposure prevention of viral entry) is an Integrated Preclinical/Clinical Program, with the overall goal to provide a comprehensive set of data to facilitate an informed decision on whether the antiviral lectin Griffithsin (GRFT) shoul progress in the topical microbicides pipeline. GRFT has broad-spectrum activity against human immunodeficiency viruses (HIV) types 1 and 2, herpes simplex virus type 2 (HSV-2) and hepatitis C virus (HCV). Our product target is a rectal microbicide gel, containing GRFT as the primary Active Pharmaceutical Ingredient (API). People who practice unprotected receptive anal intercourse (URAI) represent the population most vulnerable to HIV-1 transmission due to the high preponderance of HIV target cells in the rectal mucosa, and mucosal trauma commonly associated with RAI. As a small protein, unlikely to be widely used in antiretroviral therapy, the GRFT PREVENT program stands apart from pre-exposure prophylaxis (PREP) strategies that involve small molecule antiretrovirals (ARV), which bear the potential risk of selecting for viral resistance. Broad spectrum antiviral prophylaxis that is offered by lubricant gels containing GRFT offer a much needed option for HIV infected people who require effective PREP against superinfection with HIV as well as HSV-2, HCV and other enveloped viruses that are transmitted by URAI. Three Projects and four Cores will all contribute to the Specific Aims of the Overall Program. Aim 1: Provide a comprehensive set of safety and efficacy data to facilitate a Go/No-Go decision on progression of GRFT rectal microbicides into later stage clinical studies. Aim 2: Manage and integrate the PREVENT U19 Program with the goals and expectations of the NIH sponsor and future sponsors and investors in GRFT microbicide gel products.

描述（由申请人提供）：预防（预防病毒入口的预防预防）是一项综合临床前/临床计划，其总体目标是提供一组全面的数据，以促进有关局部微生物剂中是否进展的抗病毒凝集素Griffithsin（GRFT）的明智决定。 GRFT具有针对人类免疫缺陷病毒（HIV）1和2，单纯疱疹病毒2型（HSV-2）和丙型肝炎病毒（HCV）的广谱活性。我们的产品靶标是直肠菌心凝胶，其中包含GRFT作为主要的活性药物成分（API）。由于直肠粘膜中HIV靶细胞的高率，以及通常与RAI相关的粘膜创伤，实践无保护的接受肛门性交（URAI）代表最容易受到HIV-1传播的人群。作为一种小蛋白质，不太可能被广泛用于抗逆转录病毒疗法，GRFT防止程序与涉及小分子抗逆转录病毒（ARV）的暴露前预防（PREP）策略不同，这些策略具有选择病毒耐药性的潜在风险。含有GRFT的润滑剂凝胶提供的广谱抗病毒预防为艾滋病毒感染者提供了急需的选择，这些人需要有效的与HIV近距离感染以及HSV-2，HCV，HCV和其他由Urai传播的信封病毒。三个项目和四个核心都将有助于整个计划的具体目标。 AIM 1：提供一组全面的安全性和功效数据，以促进有关GRFT直肠菌皮进展为以后临床研究的GO/NO-GO决定。 AIM 2：管理和集成了预防U19计划与NIH赞助商和未来赞助商的目标和期望以及GRFT菌心凝胶产品中的投资者的目标和期望。