A Phase I Adaptive, Multiple Dose Pharmacokinetic and Safety Assessment of Valacyclovir in Infants at Risk of Acquiring Neonatal Herpes Simplex Virus Disease
Status: Active_not_recruiting
Location: See all (12) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY
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.
Eligibility
Participation Requirements
Sex: All
Minimum Age: 1 day
Maximum Age: 2 days
Healthy Volunteers: f
View:
• Signed informed consent from parent(s) or legal guardian(s)
• Maternal history of genital HSV infection
• Maternal receipt of oral acyclovir, valacyclovir, or famciclovir suppressive therapy for \>/= 7 days prior to delivery
• Gestational age \>/= 38 weeks at birth
• \</= 2 days of age at study enrollment\*
• Weight at study enrollment \>/= 2,000 grams
⁃ For purposes of this study, the calendar day of birth is Day of Life 0
Locations
United States
Alabama
Children's of Alabama Child Health Research Unit (CHRU)
Birmingham
Georgia
Emory University School of Medicine
Atlanta
Kentucky
University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases
Louisville
Minnesota
M Health Fairview Masonic Children's Hospital
Minneapolis
Missouri
Washington University in St. Louis
St Louis
North Carolina
Atrium Health ID Consultants & Infusion Care Specialists
Charlotte
Nebraska
Children's Nebraska
Omaha
New York
Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease
Queens
University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases
Rochester
SUNY Upstate Medical University Hospital - Pediatrics
Syracuse
Ohio
Nationwide Children's Hospital
Columbus
Wisconsin
Medical College of Wisconsin
Milwaukee
Time Frame
Start Date:2023-08-07
Completion Date:2025-09-30
Participants
Target number of participants:17
Treatments
Experimental: Cohort 1
A cohort of neonates who are at risk of acquiring neonatal herpes simplex virus disease will receive 10 mg/kg of valacyclovir will be administered orally two times daily for 5 days. N=8
Experimental: Cohort 2
If the safety profile and the drug exposure concentrations in Cohort 1 are acceptable, eight new subjects will be enrolled in Cohort 2. If the mean of observed acyclovir exposures of subjects in Cohort 1 are below 24,000 ngxhr/mL, AND if no Grade 3 or Grade 4 AEs or SAEs are detected in any of the study subjects, then the 8 subjects enrolled in Cohort 2 will receive oral valacyclovir at a dose of 20 mg/kg administered two times daily for 5 days. Alternatively, if the mean of observed acyclovir exposures of subjects in Cohort 1 are above 48,000 ngxhr/mL AND if no Grade 3 or Grade 4 AEs or SAEs are detected in any of the study subjects, then the 8 subjects enrolled in Cohort 2 will receive oral valacyclovir at a dose that has been linearly adjusted downward to target 36,000 ngxh/mL area-under-the-concentration-time curve from 0 to 12 hours (AUC12).