CLINICAL TRIAL: IMPAACT P1066 (VERSION 10) A PHASE I/II, MULTICENTER, OPEN-LAB

临床试验：IMPAACT P1066（版本 10）A I/II 期、多中心、开放实验室

• 批准号: 8356688
• 负责人: William Thomas Shearer
• 金额: $ 0.7万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356688
• 关键词: 2 year old; Acute; Adolescence; Adolescent; Age; Anti-Retroviral Agents; Biological Assay; Child; Childhood; Clinical Research; Clinical Trials; DNA-Directed DNA Polymerase; Data; Drug Interactions; Enzymes; Funding; Grant; HIV; HIV-1; Human; IMPAACT; In Vitro; Inhibitory Concentration 50; Integrase Inhibitors; Measures; Medical; National Center for Research Resources; Patients; Phase; Population; Principal Investigator; Regimen; Research; Research Infrastructure; Resistance; Resources; Ribonuclease H; Safety; Serum; Source; Therapeutic; Toxic effect; United States National Institutes of Health; Virus; antiretroviral therapy; cost; dosage; experience; human DNA; novel; open label; pre-clinical

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT There is an acute medical need for novel and potent antiretroviral therapy for HIV-infected patients who are experiencing resistance, suffer from toxicities on other possible regimens, or are failing their current antiretroviral regimen. These patients are often heavily pre-treated and have very limited or no remaining therapeutic options. The purpose of this pediatric study is to gain dosage, short and long term safety data, intensive and population PK data, drug interactions, and efficacy experience with raltegravir in HIV-1 infected children with which to guide potential usage in children ages two through adolescence. IMPAACT P1066 is a Phase I/II, multi-center, open-label, noncomparative study of approximately 120 to 140 HIV-1 infected children and adolescents ages =2 years to 1000-fold selectivity over other phosphotranferases, including the structurally related enzyme HIV-1 RNase H and the human DNA polymerases, a, ¿, and (IC50 values 50 ¿M). The antiretroviral potency of raltegravir (IC95 of 33 ¿ 23 nM; 50% human serum) measured in vitro is comparable to many clinically efficacious antiretroviral therapeutics. Inhibition of HIV-1 replication is shown to be a result of raltegravir interference with integration. Preclinical data, including in vitro inhibition assays and safety assessment, suggest that raltegravir has the promise to be a clinically safe and effective integrase inhibitor. In addition, raltegravir has been shown in Phase II and III clinical studies, to be generally well tolerated and has demonstrated potent efficacy in both treatment-na¿ve and treatment-experienced patients with triple-class resistant virus.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供 该子项目的主要支持。 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源的子项目可能列出的总成本。 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 抽象的 对于正在经历耐药性、其他可能的治疗方案出现毒性或目前的抗逆转录病毒治疗方案失败的艾滋病毒感染者来说，迫切需要新型有效的抗逆转录病毒疗法。这些患者通常经过大量预先治疗，且治疗效果非常有限。这项儿科研究的目的是获得拉替拉韦在 HIV-1 感染儿童中的剂量、短期和长期安全性数据、强化和群体 PK 数据、药物相互作用以及疗效经验，以指导潜在的使用。 IMPAACT P1066 是一项 I/II 期、多中心、开放标签、非比较性研究，对象为约 120 至 140 名 HIV-1 感染儿童和青少年（年龄 = 2 岁），选择性是其他磷酸转移酶的 1000 倍。 ，包括结构相关的酶 HIV-1 RNase H 和人类 DNA 聚合酶，a, ¿ ，（IC50 值为 50 ¿M），体外测量的拉替拉韦的抗逆转录病毒效力（IC95 为 33 ¿ 23 nM；50% 人血清）与许多临床有效的抗逆转录病毒疗法相当。是拉替拉韦干扰整合的结果。 包括体外抑制试验和安全性评估在内的临床前数据表明，拉替拉韦有望成为临床上安全有效的整合酶抑制剂。此外，拉替拉韦已在 II 期和 III 期临床研究中显示，总体耐受性良好，且具有良好的耐受性。在两种治疗中都表现出强大的功效-na¿ ve 和有治疗经验的三级耐药病毒患者。