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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 摘要 医学上迫切需要新的有效的抗逆转录病毒疗法来治疗艾滋病毒感染患者，这些患者正在经历耐药性，遭受其他可能方案的毒性，或者正在失败他们目前的抗逆转录病毒方案。这些患者通常经过严格的预治疗，治疗选择非常有限，甚至没有剩余的选择。这项儿科研究的目的是获得剂量、短期和长期安全性数据、密集和人群PK数据、药物相互作用和拉替格列韦在HIV-1感染儿童中的疗效经验，以指导2岁到青春期儿童的潜在使用。IMPAACT P1066是一项I/II期、多中心、开放标签、非比较研究，对大约120到140名感染HIV-1的儿童和青少年进行研究，年龄=2岁到1000倍于其他磷酸转移酶，包括结构相关的酶HIV-1 RNaseH和人类DNA聚合酶a、？和(IC50值50？M)。体外测定的Raltegravir(IC95为33？23 nM；50%人血清)的抗逆转录病毒效力可与许多临床有效的抗逆转录病毒疗法相媲美。抑制HIV-1复制被证明是雷替格列韦干扰整合的结果。 临床前数据，包括体外抑制试验和安全性评估，表明雷替格雷有望成为一种临床安全有效的整合酶抑制剂。此外，雷替格列韦已经在第二阶段和第三阶段临床研究中被证明是普遍耐受性良好的，并在治疗新陈代谢和治疗经验丰富的三级耐药病毒患者中显示出强大的疗效。

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.