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：
10546216
负责人：
RODNEY J.Y. HO
金额：
$ 126.01万
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 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10546216
关键词：
Adherence Adolescent Adult Anti-Retroviral Agents Back Blood Cells Child Childhood Clinical Clinical Paths Combination Drug Therapy Communication Data 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/Ritonavir Modeling National Institute of Allergy and Infectious Disease Oral Pharmaceutical Preparations Phase Plasma Plasma Cells Primates Process Proteins RNA-Directed DNA Polymerase Research Resources Route Safety Schedule Source Suspensions Technology Tenofovir Testing Therapeutic Time TimeLine Tissues United States Food and Drug Administration United States National Institutes of Health Update Water Work anti-viral efficacy antiretroviral therapy base clinical development combat first-in-human industry partner innovation interest meetings nano nanoparticle nanoparticle drug nanotechnology platform nonhuman primate novel drug combination oral HIV pediatric human immunodeficiency virus pharmacokinetic model pill preclinical development preference programs public-private partnership research and development safety study simian human immunodeficiency virus success

Adherence Adolescent Adult Anti-Retroviral Agents Back Blood Cells Child Childhood Clinical Clinical Paths Combination Drug Therapy Communication Data 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/Ritonavir Modeling National Institute of Allergy and Infectious Disease Oral Pharmaceutical Preparations Phase Plasma Plasma Cells Primates Process Proteins RNA-Directed DNA Polymerase Research Resources Route Safety Schedule Source Suspensions Technology Tenofovir Testing Therapeutic Time TimeLine Tissues United States Food and Drug Administration United States National Institutes of Health Update Water Work anti-viral efficacy antiretroviral therapy base clinical development combat first-in-human industry partner innovation interest meetings nano nanoparticle nanoparticle drug nanotechnology platform nonhuman primate novel drug combination oral HIV pediatric human immunodeficiency virus pharmacokinetic model pill preclinical development preference programs public-private partnership research and development safety study simian human immunodeficiency virus success

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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.

抽象的有针对性的，长效和组合抗逆转录病毒治疗（TLC-ART）计划已制定可伸缩的药物组合纳米平台技术，称为DCNP（药物组合纳米颗粒），该技术在可注射剂中稳定不溶性和可溶性短作用抗逆转录病毒药物暂停。在非人类灵长类在没有滞后相的血浆和细胞中可以检测到的长效组合（即快速峰值药物浓度）。该应用程序计划利用新颖的DCNP技术来开发安全有效的长效 HIV儿童的抗逆转录病毒疗法。迫切需要儿童的长效注射在依从性问题上挣扎的人，包括药丸疲劳或无法吞咽。我们已经为最先进的两个活跃药物TLC-ART平台建立了一个公私合作伙伴关系通过NIH的UM1资金进行成人治疗的评估。有了这些宝贵的资源，我们计划为儿童创建一个长效的每月可注射配方，其中包括三种活性药物针对两个HIV蛋白。我们的一组里程碑驱动的目标是基于定义的目标产品配置文件（TPP），将由外部顾问委员会（EAB）通过计划和按需会议。以研究为重点的目标（目标1和2）旨在评估一组四个不同潜在的儿科HIV-rug DCNP组合并根据少年非人类灵长类动物的研究选择候选人，以发展前临床前开发并寻求FDA加速临床进展计划的指导（目标3-6）。这项为期五年的提案将对EAB和NIAID/DAIDS计划进行监督，以确保成功，并研究结果将构成开发安全有效的长效抗病毒组合以治疗年轻的基础艾滋病毒的孩子。