Skip to main content

8602: A Phase I Adaptive, Multiple Dose Pharmacokinetic and Safety Assessment of Valacyclovir in Infants At Risk of Acquiring Neonatal Herpes Simplex Virus Disease (DMID 20-0033)


Herpes simplex virus (HSV) is a rare cause of disease in newborns, but when it occurs the outcome is usually upsetting. We recently documented that neonatal HSV disease occurs approximately 1 in 3,000 deliveries in 2000, but by 2012 had increased by almost 60% to 1 in 1,900 live births. This equals to 2,000 babies delivered each year who develop neonatal HSV disease. Neonatal HSV can be classified as disease only on the skin, eyes, and/or mouth (SEM disease), disease of the brain (CNS disease), or infection involving multiple organs (disseminated disease). Neonates with disseminated or SEM disease generally seek medical care at 10-12 days of life, while those with CNS disease on average present somewhat later at 16-19 days of life. Approximately 30% of newborns with disseminated neonatal HSV disease die despite 21 days of antiviral treatment with acyclovir by IV followed by 6 months of acyclovir by mouth, and approximately 20% of surviving babies will have lifelong developmental delays. For babies with the CNS classification of neonatal HSV disease receiving the same treatment, approximately 5% will die but one-third of survivors will have developmental delays.

No new antiviral drugs active against HSV are nearing the stage where they are available to prescribe to newborns, and use of current medicines (IV acyclovir for treatment of neonatal HSV disease followed by acyclovir by mouth) has been made the most of already. Therefore, our strategy to decrease the deaths and developmental delays caused by HSV in the newborn population has shifted to preventing newborns from being exposed to HSV in the mother’s birth canal at the time of delivery or from progressing to neonatal infection and then to neonatal disease at 10-19 days of life. The current study will provide much needed data in this prevention strategy by determining the appropriate dose of medication given by mouth that can stop the virus from growing on the skin or mucous membranes of newborns exposed to HSV at delivery, thereby preventing the HSV exposure from ever progressing to infection or neonatal HSV disease.

This study will enroll 16 babies in 2 different groups at multiple research sites in the US. A third group may be enrolled if the results from the first two groups show that more information is needed.

What Happens During This Study?

The first 8 babies (Group 1) enrolled in the study will receive study medication 2 times a day for 5 days in liquid form by mouth. The dose of medication will be based on their weight (10mg/kg). After your baby has taken the medicine, blood will be taken to see how much of the medicine is present in the blood. Following enrollment of the first 8 babies in Group 1, a special committee made of people that review the safety of data will review the data on the amount of study drug in the blood of all babies enrolled. If these data show that it was safe and gave acceptable levels in the baby’s blood, we will enroll 8 additional babies (Group 2) using a dose of medication that will be based on the information from the first babies enrolled on the study.

Should the amount of study drug in the blood from the 8 additional babies enrolled in Group 2 not be acceptable, an additional group may be enrolled at a different dose. Your doctor will tell you if your baby is one of the first eight babies (Group 1), second group of eight babies (Group 2), or the third group of babies. All babies enrolled on the study will be seen by the study staff on the same schedule and have the same procedures done each visit.

Your baby will be seen by the study team on Study Days 1 and 5. Visits on Study Days 10 and 42 may be done on the phone or in the research clinic. Visits on study Days 1, 10 and 42 will take about 1 hour. The visit on study Day 5 will require your baby to remain in the clinic area for about 8-10 hours. This will be the day we collect a small amount of blood at 4 different times to determine the amount of medication in your baby’s blood.

What will be required to participate in the study?

  • Take the medication by mouth for 5 days
  • We will review your baby’s and mother’s medical records for medical history.
  • Record all medications that your baby is taking while on the study.
  • We will collect blood to determine how your baby’s kidneys and liver are functioning.
  • We will collect blood to determine how much medication is in your baby’s body.
  • We will ask you each visit if your baby had any issues after taking the medication.

To be eligible to participate, you must:

  • Have a signed informed consent from parent(s) or legal guardian(s).
  • Mom has a history of HSV bumps in her genital area.
  • Mom received acyclovir, Valacyclovir, or famciclovir medication for7 days or more prior to delivery.
  • Age between conception and birth is 38 weeks or greater at birth.
  • 2 days of age or greater at study enrollment.
  • Weight at study enrollment 2,000 grams (2 kg) or larger.

You are not eligible to participate if you have:

  • If your baby has HSV bumps at birth.
  • Known problems with your baby’s kidneys.
  • Mom has genital lesions suspected of HSV at the time of delivery.
  • Infants born to women who are HIV positive (but HIV testing is not required for study entry).
  • Currently receiving acyclovir, ganciclovir, famciclovir, or any investigational drugs.

How to participate?

In order to participate in this study, you must contact the study coordinator or investigator of any of the participating institutions by phone or by email.