Evaluation of the pharmacokinetics of valacyclovir in subjects 1 month of age or older in order to assist in the design of a safer, more beneficial study of its pharmacokinetics in neonates under 2 weeks of age.

Evaluation of the pharmacokinetics of valacyclovir in subjects 1 month of age or older in order to assist in the design of a safer, more beneficial study of its pharmacokinetics in neonates under 2 weeks of age.

For the NIH-funded study, the research proposal summary is as follows:This study, A Phase I Adaptive, Multiple Dose Pharmacokinetic and Safety Assessment of Valacyclovir in Neonates 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. Currently, the only pediatric pharmacokinetic studies of valacyclovir were the GSK-HS210916, GSK-HS210914, and GSK-HS210915 studies, and they enrolled subjects 1 month of age and older. Neonates by definition are under 1 month of age, and in the Phase I pharmacokinetic study that we will conduct through the NIH-funded U54 Rare Diseases Consortium, we will determine the optimal valacyclovir dose in neonates under 2 weeks of age and thereby provide trial readiness for the next, larger efficacy study.

[{ "PostingID": 1933, "Title": "GSK-HS210916", "Description": "An open-label, multiple-dose, multicenter, pharmacokinetic, safety and tolerability study of valaciclovir oral suspension in infants and children with VZV infection" },{ "PostingID": 1935, "Title": "GSK-HS210914", "Description": "An open-label, single-dose, multicenter, pharmacokinetic, safety and tolerability study of valaciclovir oral suspension in infants and children." },{ "PostingID": 1936, "Title": "GSK-HS210915", "Description": "An open-label, multiple-dose, multicenter, pharmacokinetic, safety and tolerability study of valaciclovir oral suspension in infants and children with HSV infection" }]