Valacyclovir Phase I Trial

伐昔洛韦 I 期试验

基本信息

批准号：
10248359
负责人：
DAVID W KIMBERLIN
金额：
$ 22.59万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
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/10248359
关键词：
Acquired Immunodeficiency Syndrome Acyclovir Adult Adverse event Age-Months Alanine Transaminase Antiviral Agents Antiviral Therapy Biological Assay Biological Availability Birth Cessation of life Child Clinical Research Collaborations Congenital herpes simplex Creatinine Data Development Diagnostic Diagnostic tests Disease Dose Drug Kinetics Enrollment Event Exposure to Funding Future Goals Hemoglobin 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 Virus Virus Diseases Visit White Blood Cell Count procedure Woman age group base congenital infection detection platform diagnostic platform efficacy study emotional distress genital infection high risk mortality mortality risk neonatal infection neonate novel older patient overtreatment 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

项目摘要

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.

这项研究，I期自适应，多剂量药代动力学和对Valacyclovir的安全评估大卫·金伯林（David W. 单纯疱疹病毒（HSV）是新生儿疾病的罕见原因，但是当疱疹经常发生结果时是毁灭性的。尽管过去三十年来在新生儿HSV治疗中取得了重要进展疾病，大量婴儿死亡或留下终身神经系统后遗症。而抗病毒干预措施的结果改善非常重要，这是避免的最佳机制死亡，神经系统损害和新生儿HSV的情绪困扰是为了防止这种疾病发生首先。由于有85％的婴儿在出生期间从母亲那里获取病毒过程，检测哪些女性脱落HSV将允许采用理性的，有针对性的方法那些有风险的新生儿。但是，为了实现这一目标，一个简单，标准化的快速测试用于检测HSV 需要在分娩时生殖道，以及可以在需要暴露于HSV以防止HSV疾病发展的新生儿。迈向迈向采用这种方法，我们已经完成了一项由NIH资助的研究，并与 Cepheid Inc.，使用公司的新型护理聚合酶链反应（PCR）测定 XPERT诊断平台，用于在分娩时阴道拭子中检测HSV DNA （ClinicalTrials.gov标识符NCT01878383）。尽管这项研究是重要的诊断进步，但我们的最终目标是评估先发制人的抗病毒 XPERT PCR评估对母亲阴道的评估检测到的婴儿在分娩时暴露于HSV的婴儿的治疗拭子，可以防止在传递时从发展到新生儿HSV感染，从而防止HSV暴露于新生儿 HSV病。为了评估这一点，我们需要在暴露于HSV的新生儿中进行III期治疗研究使用口服Valacyclovir（由于其具有优质的口服生物利用度，与口服Acyclovir相比）。之前但是，这是我们需要知道对新生儿施用的valaceclovir剂量我们先前在已经获得HSV感染的婴儿中鉴定出的Acyclovir暴露。我们因此，将通过先天性和围产期感染进行I期药代动力学研究联盟（CPIC）确定最佳valacyclovir剂量，从而为下一个提供试验准备就绪更大的功效研究。