PHASE I STUDY OF PHARMACOKINETICS, SAFETY AND ACCEPTABILITY OF A SINGLE DOSE OF PRETOMANID ADDED TO AN OPTIMIZED BACKGROUND REGIMEN IN CHILDREN WITH RIFAMPICIN RESISTANT TUBERCULOSIS IMPAACT 2034

对患有利福平耐药结核病儿童的单剂量 Pretomanid 的药代动力学、安全性和可接受性的 I 期研究添加到优化背景方案中的影响 2034

• 批准号: 10679271
• 负责人: BARBARA DRIVER
• 金额: $ 29.94万
• 依托单位: WESTAT, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-03 至 2025-12-15
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679271
• 关键词: 18 year old; AIDS clinical trial group; AIDS prevention; AIDS/HIV problem; Adolescent; Adult; Aftercare; Anti-Retroviral Agents; Area; Body Weight; Child; Childhood; Clinical Trials; Collaborations; Communities; Conduct Clinical Trials; Development; Disease remission; Dose; Drug Kinetics; Enrollment; Epidemic; Formulation; Future; Goals; HIV; HIV Infections; HIV therapy; Individual; Infant; Infection; Institution; International Maternal Pediatric Adolescent AIDS Clinical Trials; Intervention; Leadership; Light; Monitor; National Institute of Allergy and Infectious Disease; National Institute of Child Health and Human Development; Opportunistic Infections; Oral; Participant; Passive Immunotherapy; Pharmaceutical Preparations; Postpartum Women; Pregnant Women; Prevention; Process; Protocols documentation; Regimen; Research; Research Personnel; Research Priority; Resources; Rifampicin resistance; Safety; Science; Site; Symptoms; Tablets; Testing; Therapeutic Agents; Time; Treatment Protocols; Tuberculosis; Vaccines; Vertical Disease Transmission; Work; antiretroviral therapy; base; co-infection; infection rate; perinatal HIV; phase 1 study; pregnant; prevent; study population; synergism; targeted treatment; therapeutic vaccine; transmission process; tuberculosis treatment; young woman

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides clinical trial sites to the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT). The IMPAACT network and its leadership group oversee the creation of all their studies, protocols, and clinical trials. The IMPAACT Network is a cooperative group of institutions, investigators, and other collaborators mainly focused on evaluating potential therapies for HIV infection and its related symptoms and co-infections in infants, children, adolescents, and pregnant women. This includes clinical trials of HIV/AIDS interventions for the prevention of mother to child transmission. The IMPAACT Network goal is to conduct high quality clinical trials and/or protocols that will advance the prevention and treatment of HIV and its complications for infants, children, adolescents, and pregnant/ postpartum women globally. The IMPAACT research agenda in this task order includes four scientific specific aims, which reflect the key areas of work. Those areas are HIV Treatment, HIV Prevention, HIV Cure, and HIV Complications. For each area, a Scientific Committee composed of experts in the specific field, site investigators, community representatives, and representatives of the central network resources, continually reassesses the research priorities in light of emerging science as well as new ideas and opportunities; it seeks collaboration with other trials networks and research entities; oversees the formulation and review of study concept plans based on the scientific priorities; and monitors the development and implementation of approved network studies in the specific research area. In 1990 the NICHD began collaborating with the AIDS Clinical Trials Group (ACTG) and subsequently, in 1996 with the Pediatric AIDS Clinical Trials Group (PACTG) to expand clinical trial availability at NICHD clinical trial centers/sites. This collaboration made it possible to conduct clinical trials by the IMPAACT Network to further evaluate anti-retroviral therapeutic agents, other therapies targeted at opportunistic infections, and interventions to prevent perinatal HIV transmission. In recent years, the collaboration is expanding to evaluate potential HIV cure approaches and vaccines. For the last 35 years, NICHD and the National Institute of Allergy and Infectious Diseases (NIAID), as part of the scientific community, have been conducting intense HIV research. During this time, it became clear that to be successful in the attempt to curb the HIV infection rates of the epidemic, and appropriately treat the individual infectious process, an integrated and comprehensive approach to HIV research is required. Furthermore, NICHD/NIAID and others in the scientific community found in the mid-90s that one or even two different anti-retroviral drugs (ARVs) are not sufficient to appropriately treat an individual HIV infection. Therefore, the synergy of three or more drugs (ARVs) is required to effectively treat and keep at bay an individual HIV infection. For that reason, the development and testing of multiple ARVs in different trials are essential. At the same time, as soon as a drug was developed and approved, multiple other trials were needed to discern the potential synergy between them. It is now known to the scientific community that the initial attempts to achieve an HIV Cure (remission) might require the interaction of multiple ARVs, in addition to an early start in the treatment after infection (plus the potential use of passive immunotherapy plus long-term acting anti-retroviral therapy) and even therapeutic vaccines.

尤尼斯·肯尼迪·施赖弗国家儿童健康和人类发展研究所 (NICHD) 为国际孕产妇儿科青少年艾滋病临床试验组 (IMPAACT) 提供临床试验场所。 IMPAACT 网络及其领导小组负责监督所有研究、方案和临床试验的创建。 IMPAACT 网络是一个由机构、研究人员和其他合作者组成的合作小组，主要致力于评估婴儿、儿童、青少年和孕妇的 HIV 感染及其相关症状和合并感染的潜在疗法。这包括预防母婴传播艾滋病毒/艾滋病干预措施的临床试验。 IMPAACT 网络的目标是开展高质量的临床试验和/或方案，以促进全球婴儿、儿童、青少年和孕妇/产后妇女的艾滋病毒及其并发症的预防和治疗。该任务顺序中的 IMPAACT 研究议程包括四个科学具体目标，反映了工作的关键领域。那些地区 包括艾滋病毒治疗、艾滋病毒预防、艾滋病毒治愈和艾滋病毒并发症。对于每个领域，由特定领域的专家、现场调查员、社区代表和中央网络资源代表组成的科学委员会，根据新兴科学以及新的想法和机会不断重新评估研究重点；它寻求与其他试验网络和研究实体的合作；根据科学优先事项监督研究概念计划的制定和审查；并监督特定研究领域经批准的网络研究的开发和实施。 1990 年，NICHD 开始与艾滋病临床试验小组 (ACTG) 合作，随后于 1996 年与儿科艾滋病临床试验小组 (PACTG) 合作，以扩大 NICHD 临床试验中心/场所的临床试验可用性。此次合作使得 IMPAACT 网络能够进行临床试验，以进一步评估抗逆转录病毒治疗药物、针对机会性感染的其他疗法以及预防围产期的干预措施 艾滋病毒传播。近年来，合作范围正在扩大，以评估潜在的艾滋病毒治疗方法和疫苗。 过去 35 年来，NICHD 和国家过敏和传染病研究所 (NIAID) 作为科学界的一部分，一直在开展深入的艾滋病毒研究。 在此期间，人们清楚地认识到，要成功遏制该流行病的艾滋病毒感染率并适当对待个体感染过程，就需要对艾滋病毒研究采取综合全面的方法。此外，NICHD/NIAID 和科学界的其他人在 90 年代中期发现，一种甚至两种不同的抗逆转录病毒药物 (ARV) 不足以适当治疗个体 HIV 感染。因此，需要三种或多种药物（ARV）的协同作用才能有效治疗和预防个体艾滋病毒感染。因此，在不同的试验中开发和测试多种抗逆转录病毒药物至关重要。与此同时，药物一旦开发出来并获得批准，就需要进行多项其他试验来辨别它们之间潜在的协同作用。 现在科学界知道，除了感染后尽早开始治疗（加上可能使用被动免疫疗法和长期治疗）之外，实现艾滋病毒治愈（缓解）的初步尝试可能需要多种抗逆转录病毒药物的相互作用。术语抗逆转录病毒疗法）甚至治疗性疫苗。