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.

这项研究是伐昔洛韦的 I 期适应性、多剂量药代动力学和安全性评估面临新生儿单纯疱疹病毒病风险的婴儿由医学博士 David W. Kimberlin 领导。单纯疱疹病毒 (HSV) 是新生儿疾病的一种罕见原因，但当它发生时，结果往往会出现是毁灭性的。尽管过去三十年在新生儿 HSV 治疗方面取得了重要进展疾病，大量婴儿死亡或留下终生神经系统后遗症。虽然抗病毒干预措施的结果得到显着改善，这是避免病毒感染的最佳机制新生儿 HSV 导致的死亡、神经系统损伤和情绪困扰是为了预防该疾病的发生首先。由于 85% 患有新生儿 HSV 疾病的婴儿是在出生时从母亲那里获得病毒的过程中，检测哪些女性正在感染 HSV 将有助于采取合理、有针对性的方法，重点关注那些处于危险之中的新生儿。然而，为了实现这一目标，需要一种简单、标准化、快速的检测方法来检测 HSV 需要在分娩时对母体生殖道进行检查，并且可以使用治疗干预需要让新生儿接触 HSV 以预防 HSV 疾病的发生。迈出了重要的一步为了实现这种方法，我们已经完成了一项由 NIH 资助的研究的招募，与 Cepheid Inc.，使用该公司的技术验证一种新型即时护理聚合酶链式反应 (PCR) 检测 Xpert诊断平台用于检测孕妇分娩时阴道拭子中的HSV DNA （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性抗病毒药物是否有效对分娩时暴露于 HSV 的婴儿进行治疗（通过 Xpert PCR 评估产妇阴道检测）拭子，可以防止分娩时 HSV 暴露发展为新生儿 HSV 感染，从而预防新生儿单纯疱疹病毒疾病。为了评估这一点，我们需要对接触 HSV 的新生儿进行 III 期治疗研究分娩时使用口服伐昔洛韦（由于与口服阿昔洛韦相比，其口服生物利用度更高）。之前不过，我们需要知道给新生儿服用多少剂量的伐昔洛韦才能安全地提供目标作用我们之前在已经感染 HSV 的婴儿中发现了阿昔洛韦暴露。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) 确定最佳伐昔洛韦剂量，从而为下一步试验做好准备，更大规模的疗效研究。