Clinical trial NCT05468619: Neonatal Phase 1 Valacyclovir Study
Official title: A Phase I Adaptive, Multiple Dose Pharmacokinetic and Safety Assessment of Valacyclovir in Infants at Risk of Acquiring Neonatal Herpes Simplex Virus Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Herpes Simplex
Keywords: Disease
Herpes Simplex Virus
Neonatal
Phase I
Valacyclovir
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2022-07-21
Enrollment: 16
Sex: ALL
Minimum age (years): 1
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Neonatal plasma acyclovir mean AUC12 concentrations
timeFrame: Days 1 - 5
Secondary outcomes:
measure: Half-life (t1/2) of acyclovir
timeFrame: Days 1 - 5
measure: Maximum Serum Concentration (Cmax) of acyclovir
timeFrame: Days 1 - 5
measure: Occurrence of Grade 3 Adverse Events (AEs)
timeFrame: Days 1 - 42
measure: Occurrence of Grade 4 Adverse Events and Serious Adverse Events
timeFrame: Days 1 - 42
measure: Oral Clearance (CL/F) of acyclovir
timeFrame: Days 1 - 5
measure: Time to the maximum concentration (Tmax) of acyclovir
timeFrame: Days 1 - 5
measure: Volume of distribution (V/F) of acyclovir
timeFrame: Days 1 - 5
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama Child Health Research Unit (CHRU)
state: Alabama
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Louisville
country: United States
facility: University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases
state: Kentucky
city: Minneapolis
country: United States
facility: M Health Fairview Masonic Children's Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: Children's Nebraska
state: Nebraska
city: Queens
country: United States
facility: Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital - Pediatrics
state: New York
city: Charlotte
country: United States
facility: Atrium Health ID Consultants & Infusion Care Specialists
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
References: