Diseases Studied

The purpose of this study is to get a better understanding of what causes neonatal viral sepsis and to assess the impact of the infection on the babies' health over time. Enterovirus (EV) or human parechovirus (HPeV) are very common viruses that can cause neonatal viral sepsis. Information gained from this study may guide diagnosis and treatment of babies with neonatal viral sepsis in the future. This study will observe babies with neonatal EV or HPeV sepsis to assess and characterize the complications affecting them. The study will also identify key clinical measurements and tests that help predict the health outcomes of children with neonatal EV and HPeV sepsis. Further, although EV and HPeV are common causes of neonatal viral sepsis, this study seeks to identify other unknown viruses linked to neonatal viral sepsis. The information generated by this study will lay the foundation for clinical trial studies of antiviral drugs to treat neonatal viral sepsis.

The purpose of this study is to evaluate at-risk babies to determine the appropriate dose of oral valacyclovir comparable to the intravenous (IV) acyclovir doses typically used to treat babies with neonatal Herpes Simplex Virus (HSV) disease. IV acyclovir is best for the treatment of babies who already have HSV disease, but it is not ideal to prevent HSV disease because there are risks associated with IV use in babies. Valacyclovir is metabolized to become acyclovir, and although it has been studied in babies as young as one month old, there are no dosing recommendations for those less than three months old. This study focuses on at-risk babies whose mothers have a history of genital HSV infection and have been taking oral acyclovir or valacyclovir for several weeks before delivery. By studying the blood concentration, metabolism, clearance and safety profile of valacyclovir in infants less than one month old, we will determine the best dose of valacyclovir to prevent HSV infection when babies are exposed to it at birth. We will also inform larger studies using valacyclovir to treat neonatal HSV disease.

Congenital cytomegalovirus (CMV) infection is common and the leading viral cause of sensorineural hearing loss (SNHL) and mental retardation in infants. Despite current treatment options, babies with symptomatic congenital CMV disease are still at risk for hearing loss and neurologic deficits. Letermovir is the first new antiviral treatment of CMV to be licensed in over two decades. Two groups will be enrolled, and letermovir will be administered for 14 days in subjects in both groups. All subjects also will receive valganciclovir as standard of care. Group 1 (n=4) will be given a single dose based on their weight of letermovir on Study Day 0, with a full PK profile obtained over the next 24 hours to verify that the selected dose does not exceed the targeted exposure. Blood specimens will be shipped within approximately 24 hours to the UAB Pharmacokinetic Lab and processed in real time in order to get results back to the study site within an anticipated 7 days. If the drug levels are acceptable, the subject begin a 14-day course of once daily oral letermovir. If the dose is not acceptable, the dose will be adjusted down in 2.5mg increments. Once 4 subjects have been enrolled in group 1, the data and safety monitoring board will review all safety and drug level data. If no concerns are identified, then 8 additional subjects will be enrolled in group 2. The group 2 subject will start the 14 day course of study medication. The dose for group will be based on the data reviewed by the safety committee for the group 1 subjects.

Congenital cytomegalovirus (CMV) infection is the leading non-genetic cause of sensorineural hearing loss (SNHL) and the most frequent viral cause of mental retardation. Approximately 10% of infants born with CMV infection are symptomatic at birth, and of these, one-third will develop SNHL and two-thirds will experience developmental delays. A previous clinical trial run by the Collaborative Antiviral Study Group (CASG study 112) studied babies with congenital CMV infection who received either 6 weeks or 6 months of oral valganciclovir therapy. The results from this study suggested that 6 months of oral valganciclovir improved measures of neurodevelopment and hearing compared to 6 weeks of the treatment. The purpose of the current study is to assess participants from previous CASG studies and patients treated clinically for cCMV. The goal is to determine if there are long-term benefits of antiviral therapy on hearing and neurodevelopmental outcomes. Further, the current study will examine the long-term safety profile of valganciclovir when administered during infancy by assessing reports of cancer diagnoses and signs of puberty.