Neonatal Phase 1 Valacyclovir Study

National Institute of Allergy and Infectious Diseases (NIAID)17 enrolled

Overview

A Phase 1 study that will determine the valacyclovir dose that results in a systemic acyclovir exposure comparable to 10 mg/kg of parenterally administered acyclovir, which is an AUC0-12 of 24,000 ngxhr/mL to 48,000 ngxhr/mL. Neonates at risk of acquiring neonatal HSV will be enrolled in one of 2 cohorts. Cohort 1 will be comprised of eight subjects who will receive an initial dose of 10ml/kg of oral valacyclovir. Samples for PK assessments will be obtained to assess the exposure concentration. If the safety profile and the drug exposure concentrations in Cohort 1 are acceptable, eight new subjects will be enrolled in Cohort 2. The dose that these subjects will receive will be predicated upon the pharmacokinetic data from Cohort 1.

A Phase 1, open label multicenter trial to assess the safety and pharmacokinetics (PKs) of oral valacyclovir in neonates who are at risk of acquiring neonatal herpes simplex virus disease. This study will determine the valacyclovir dose that results in a systemic acyclovir exposure comparable to 10 mg/kg of parenterally administered acyclovir, which is an AUC0-12 of 24,000 ngxhr/mL to 48,000 ngxhr/mL. Neonates whose mothers have a history of genital HSV infection and received oral valacyclovir in the last several weeks of pregnancy, as per the recommendations of the American College of Obstetrics and Gynecology (ACOG) (9), will be eligible for enrollment. Cohort 1 will be comprised of eight subjects. Following informed consent, each subject will receive 10 mg/kg of oral valacyclovir, and may start taking oral valacyclovir while still in the birth hospital, with subsequent dosing at home, or may start taking oral valacyclovir following discharge from the birth hospital. If the safety profile and the drug exposure concentrations in Cohort 1 are acceptable, eight new subjects will be enrolled in Cohort 2. The dose that these subjects will receive will be predicated upon the pharmacokinetic data from Cohort 1. The primary study objective is to establish the dose of valacyclovir in neonates that reliably achieves systemic acyclovir exposures comparable to 10 mg/kg of parenterally administered acyclovir. The secondary study objectives are: 1) to define the pharmacokinetic profile of acyclovir in neonates receiving oral valacyclovir and 2) to assess and describe the safety profile of valacyclovir among treated neonates.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Eligibility

Sex: ALLMin age: 1 DayMax age: 2 Days

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed informed consent from parent(s) or legal guardian(s) 2. Maternal history of genital HSV infection 3. Maternal receipt of oral acyclovir, valacyclovir, or famciclovir suppressive therapy for \>/= 7 days prior to delivery 4. Gestational age \>/= 38 weeks at birth 5. \</= 2 days of age at study enrollment\* 6. Weight at study enrollment \>/= 2,000 grams * For purposes of this study, the calendar day of birth is Day of Life 0 Exclusion Criteria: 1. Evidence of neonatal HSV infection 2. Evidence of sepsis 3. Known renal anomalies or dysfunction 4. Maternal genital lesions suspicious for HSV at the time of delivery 5. Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry) 6. Current receipt in the neonate of acyclovir, ganciclovir, famciclovir, or any investigational drugs

Locations (12)

Children's of Alabama Child Health Research Unit (CHRU)

Birmingham, Alabama, United States

Emory University School of Medicine

Atlanta, Georgia, United States

University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases

Louisville, Kentucky, United States

M Health Fairview Masonic Children's Hospital

Minneapolis, Minnesota, United States

Washington University in St. Louis

St Louis, Missouri, United States

Children's Nebraska

Omaha, Nebraska, United States

Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease

Queens, New York, United States

University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases

Rochester, New York, United States

SUNY Upstate Medical University Hospital - Pediatrics

Syracuse, New York, United States

Atrium Health ID Consultants & Infusion Care Specialists

Charlotte, North Carolina, United States

...and 2 more locations

Outcomes

Primary Outcomes

Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC12) of Acyclovir in Plasma

Pharmacokinetics (PK) parameters were estimated from the Acyclovir plasma concentration-time data after one of the doses received on Study Day 5 (window: Study Day 4 through Study Day 5 around either dose 7, 8, 9, or 10 of the study drug; samples were only collected after one of these doses) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. As blood was only collected up to 8-10 hours post dose, log-linear interpolation was used to calculate the AUC12.