Neonatal Phase 1 Valacyclovir Study

Herpes Simplex Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05468619
• Other study ID #: 20-0033
• Status: Recruiting
• Phase: Phase 1
• Start date: September 23, 2022
• Est. completion date: November 29, 2024

Study information

• Verified date: April 2024
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: David W. Kimberlin
• Phone: 12059966097
• Email: dkimberlin[@]peds.uab.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: November 29, 2024
• Est. primary completion date: November 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 2 Days

Eligibility

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

Related Conditions & MeSH terms

• Herpes Simplex

Intervention

Drug:
• Valacyclovir
Valacyclovir is a L-valyl ester of acyclovir.

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Children's of Alabama Child Health Research Unit (CHRU)	Birmingham	Alabama
United States	Atrium Health ID Consultants & Infusion Care Specialists	Charlotte	North Carolina
United States	Ohio State University - Wexner Medical Center - Infectious Diseases Clinic	Columbus	Ohio
United States	University of Texas Southwestern Medical Center - Pediatrics	Dallas	Texas
United States	University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	M Health Fairview Masonic Children's Hospital	Minneapolis	Minnesota
United States	University of Nebraska Medical Center - Children's Hospital and Medical Center - Infectious Diseases	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	Washington University in St. Louis	Saint Louis	Missouri
United States	SUNY Upstate Medical University Hospital - Pediatrics	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neonatal plasma acyclovir mean AUC12 concentrations	To establish the dose of valacyclovir in neonates that reliably achieves systemic acyclovir exposures comparable to 10 mg/kg of parenterally administered acyclovir. Acyclovir target concentration of following oral valacyclovir dosing is 24,000 ngxhr/mL to 48,000 ngxhr/mL.	Days 1 - 5
Secondary	Half-life (t1/2) of acyclovir	To define the pharmacokinetic profile of acyclovir in neonates receiving oral valacyclovir	Days 1 - 5
Secondary	Maximum Serum Concentration (Cmax) of acyclovir	To define the pharmacokinetic profile of acyclovir in neonates receiving oral valacyclovir	Days 1 - 5
Secondary	Occurrence of Grade 3 Adverse Events (AEs)	To assess and describe the safety profile of valacyclovir among treated neonates	Days 1 - 42
Secondary	Occurrence of Grade 4 Adverse Events and Serious Adverse Events	To assess and describe the safety profile of valacyclovir among treated neonates	Days 1 - 42
Secondary	Oral Clearance (CL/F) of acyclovir	To define the pharmacokinetic profile of acyclovir in neonates receiving oral valacyclovir	Days 1 - 5
Secondary	Time to the maximum concentration (Tmax) of acyclovir	To define the pharmacokinetic profile of acyclovir in neonates receiving oral valacyclovir	Days 1 - 5
Secondary	Volume of distribution (V/F) of acyclovir	To define the pharmacokinetic profile of acyclovir in neonates receiving oral valacyclovir	Days 1 - 5