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NextGen Long-acting and targeted combination ART for Children with HIV

NextGen 针对艾滋病毒儿童的长效靶向组合 ART

基本信息

批准号：
10610951
负责人：
RODNEY J.Y. HO
金额：
$ 142.45万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-06 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10610951
关键词：
Abbreviations Acceleration Adherence Adolescent Adult Anti-Retroviral Agents Blood Cells Child Childhood Clinical Clinical Paths Combination Drug Therapy Combined Modality Therapy Communication Data Data Set Deglutition Development Development Plans Disease Dosage Forms Dose Drug Combinations Drug Kinetics Drug Targeting Ensure Evaluation Exhibits FDA approved Fatigue Formulation Funding Generic Drugs HIV HIV Integrase HIV Protease Human body Injectable Integrase Integrase Inhibitors Investigational Drugs Lead Lopinavir Lopinavir/Ritonavir Marketing Modeling National Institute of Allergy and Infectious Disease Oral Pharmaceutical Preparations Phase Plasma Primates Process Proteins RNA-Directed DNA Polymerase Recommendation Research Resources Ritonavir Route Safety Schedule Source Specific qualifier value Suspensions Technology Tenofovir Testing Therapeutic Time Tissues United States Food and Drug Administration United States National Institutes of Health Update Validation Viral Water Work anti-viral efficacy antiretroviral therapy clinical development combat drug action first-in-human industry partner innovation interest large scale production meetings nano nanoparticle nanotechnology platform nonhuman primate novel drug combination oral HIV pediatric human immunodeficiency virus pharmacokinetic model physiologically based pharmacokinetics pill preclinical development preference programs public-private partnership research and development safety study simian human immunodeficiency virus success technology platform timeline

项目摘要

ABSTRACT The Targeted, Long-acting and Combination Anti-Retroviral Therapeutic (TLC-ART) Program has developed a scalable, drug-combination nano-platform technology called DcNPs (drug combination nanoparticles) that enables the stabilizing of insoluble and soluble short-acting antiretroviral drugs together in an injectable suspension. In nonhuman primates, DcNP is able to transform short-acting oral HIV-drug combinations into long-acting combinations that can be detected in plasma and cells with no lag phase (i.e., rapid peak drug concentrations). This application plans to leverage the novel DcNP technology to develop a safe and effective long-acting combination antiretroviral therapy for children with HIV. A long-acting injectable is urgently needed for children who struggle with adherence issues, including pill fatigue or an inability to swallow. We have established a public-private partnership for the most advanced two active drug TLC-ART platform evaluation intended for adult treatment through UM1 funding from the NIH. With these invaluable resources, we plan to create a long-acting monthly injectable formulation for children that includes three active drugs targeted to two HIV proteins. Our set of milestone-driven aims is based on a defined target product profile (TPP), and will be guided by an external advisory board (EAB) through scheduled and on-demand meetings. The research-focused objectives (Aims 1 and 2) are intended to evaluate a set of four different potential pediatric HIV-drug DcNP combinations and to select a candidate based on studies in juvenile non-human primates to progress to pre-clinical development and seek FDA guidance for an accelerated clinical progression plan (Aims 3-6). The five-year proposal will have EAB and NIAID/DAIDS program oversight to ensure success, and the study results will form a basis to develop safe and effective long-acting antiviral combinations for treatment of young children with HIV.

抽象的靶向、长效、联合抗逆转录病毒治疗（TLC-ART）计划已开发一种可扩展的药物组合纳米平台技术，称为 DCNP（药物组合纳米颗粒），能够在注射剂中同时稳定不溶性和可溶性短效抗逆转录病毒药物暂停。在非人类灵长类动物中，DcNP 能够将短效口服 HIV 药物组合转化为可以在血浆和细胞中检测到的长效组合，没有滞后期（即快速达峰药物浓度）。该申请计划利用新颖的DcNP技术开发一种安全有效的长效药物对感染艾滋病毒的儿童进行联合抗逆转录病毒治疗。儿童急需长效注射剂那些因依从性问题而苦苦挣扎的人，包括药物疲劳或无法吞咽。我们建立了最先进的两种活性药物TLC-ART平台的公私合作伙伴关系旨在通过 NIH 的 UM1 资助进行成人治疗的评估。有了这些宝贵的资源，我们计划为儿童开发一种长效每月注射制剂，其中包含三种活性药物靶向两种 HIV 蛋白。我们的一系列里程碑驱动的目标基于明确的目标产品概况 (TPP)，并将以通过定期和按需会议召开外部顾问委员会 (EAB)。以研究为中心的目标（目标 1 和 2）旨在评估一组四种不同的潜在儿童 HIV 药物 DCNP 组合并根据幼年非人类灵长类动物的研究选择候选者以进入临床前阶段开发并寻求 FDA 指导以加速临床进展计划（目标 3-6）。该五年提案将由 EAB 和 NIAID/DAIDS 项目监督以确保成功，并且该研究结果将为开发用于治疗青少年的安全有效的长效抗病毒组合奠定基础感染艾滋病毒的儿童。