Valacyclovir Phase I Trial

伐昔洛韦 I 期试验

• 批准号: 10465120
• 负责人: DAVID W KIMBERLIN
• 金额: $ 20.76万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10465120
• 关键词: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Adverse event; Age Months; Alanine Transaminase; Antiviral Therapy; Biological Assay; Biological Availability; Birth; Cessation of life; Child; Classification; Clinical Research; Collaborations; Congenital herpes simplex; Creatinine; Data; Development; Diagnostic; Diagnostic tests; Disease; Dose; Drug Kinetics; Enrollment; Event; Exposure to; Funding; Future; Goals; Hemoglobin; Herpes Simplex Infections; Incidence; Infant; Infection; Intervention; Label; Laboratories; Left; Modeling; Morbidity - disease rate; Mothers; Myelosuppression; Nervous System Trauma; Neurologic; Onset of illness; Oral; Oral Administration; Outcome; Perinatal; Perinatal Infection; Phase; Placebos; Platelet Count measurement; Polymerase Chain Reaction; Population; Pregnant Women; Process; Prodrugs; Rare Diseases; Recommendation; Research; Risk; Safety; Sampling; Simplexvirus; Standardization; Swab; Symptoms; Telephone; Testing; Therapeutic Intervention; Time; Toxic effect; Treatment Efficacy; United States National Institutes of Health; Vagina; Viral; Virus; Virus Diseases; Visit; White Blood Cell Count procedure; Woman; age group; congenital infection; detection platform; diagnostic platform; efficacy study; emotional distress; genital infection; high risk; improved; mortality; mortality risk; neonatal infection; neonate; novel; older patient; phase 3 study; phase I trial; point of care; point-of-care diagnostics; prevent; rapid test; reproductive tract; safety assessment; standard care; transmission process; trial readiness; unethical; valacyclovir; viral DNA

This study, A Phase I Adaptive, Multiple Dose Pharmacokinetic and Safety Assessment of Valacyclovir in Infants at Risk of Acquiring Neonatal Herpes Simplex Virus Disease, is led by David W. Kimberlin, MD. Herpes simplex virus (HSV) is a rare cause of disease in neonates, but when it occurs the results frequently are devastating. Despite important advances over the past thirty years in the treatment of neonatal HSV disease, significant numbers of babies die or are left with lifelong neurologic sequelae. While the improvements in outcomes from antiviral interventions have been significant, the best mechanism of averting death, neurologic damage, and emotional distress from neonatal HSV is to prevent the disease from occurring in the first place. Since 85% of babies developing neonatal HSV disease acquire the virus from their mothers during the birth process, detecting which women are shedding HSV would allow a rational, targeted approach focusing on those neonates at risk. To accomplish this, however, a simple, standardized, rapid test for detecting HSV in the maternal genital tract at the time of delivery is required, and a therapeutic intervention that can be used in neonates exposed to HSV to prevent HSV disease from developing is needed. In a major step toward accomplishing such an approach, we have completed enrolling an NIH-funded study, in collaboration with Cepheid Inc., to validate a novel point-of-care polymerase chain reaction (PCR) assay using the company's Xpert diagnostic platform for the detection of HSV DNA in vaginal swabs of pregnant women at delivery (ClinicalTrials.gov Identifier NCT01878383). While this study is an important diagnostic advance, our ultimate goal is to assess whether preemptive antiviral treatment of babies exposed to HSV at delivery, as detected by Xpert PCR assessment of a maternal vaginal swab, can prevent HSV exposure at delivery from progressing to neonatal HSV infection and thus to neonatal HSV disease. To assess this, we will need to conduct a Phase III treatment study in neonates exposed to HSV at delivery using oral valacyclovir (due to its superior oral bioavailability compared with oral acyclovir). Prior to this, though, we need to know what dose of valacyclovir administered to neonates safely provides the targeted acyclovir exposure that we identified previously in babies who already have acquired HSV infection. We therefore will conduct a Phase I pharmacokinetic study through the Congenital and Perinatal Infections Consortium (CPIC) to determine the optimal valacyclovir dose and thereby provide trial readiness for the next, larger efficacy study.

本研究为万乃洛韦的I期适应性、多剂量药代动力学和安全性评价 婴儿感染新生儿单纯疱疹病毒病的风险，由医学博士大卫·W·金伯林领导。 单纯疱疹病毒(HSV)是一种罕见的新生儿疾病，但当它发生时，结果经常发生 是毁灭性的。尽管过去30年来新生儿单纯疱疹病毒的治疗取得了重大进展 随着疾病的发展，大量婴儿死亡或留下终生神经后遗症。而当 抗病毒干预的结果得到了显著的改善，这是避免 新生儿单纯疱疹病毒引起的死亡、神经损伤和精神痛苦是预防疾病发生的关键 首先。 由于85%患有新生儿单纯疱疹病毒病的婴儿在出生时从母亲那里感染了病毒 过程中，检测哪些女性正在减少HSV将允许一种理性的、有针对性的方法，专注于 那些处于危险中的新生儿。然而，为了实现这一点，一种简单、标准化、快速的检测HSV的方法 需要分娩时的产妇生殖道，以及可用于 新生儿暴露于HSV以防止HSV病的发生是必要的。在迈向 为了实现这种方法，我们已经完成了一项由NIH资助的研究，并与 Cepheid Inc.，验证一种新的护理点聚合酶链式反应(PCR)分析方法，该方法使用该公司的 孕妇分娩时阴道拭子中HSV DNA检测的XPERT诊断平台 (ClinicalTrials.gov标识符NCT01878383)。 虽然这项研究是一项重要的诊断进展，但我们的最终目标是评估先发制人的抗病毒 分娩时暴露于HSV的婴儿的治疗--通过Xpert聚合酶链式反应对产妇阴道的检测 拭子，可以防止在分娩时接触HSV进展为新生儿HSV感染，从而防止新生儿 单纯疱疹病毒病。为了评估这一点，我们需要对接触HSV的新生儿进行第三阶段治疗研究 分娩时使用口服万乃洛韦(由于其口服生物利用度高于口服阿昔洛韦)。在.之前 然而，我们需要知道给新生儿安全使用多少剂量的万乃洛韦可以提供靶向。 我们之前在已经感染了HSV的婴儿中发现了阿昔洛韦的暴露。我们 因此将通过先天感染和围产期感染进行I期药代动力学研究 联盟(CPIC)，以确定万乃洛韦的最佳剂量，从而为下一次， 更大规模的疗效研究。