Valacyclovir in Neonatal Herpes Simplex Virus Disease

NCT ID: NCT04448392

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-01
• Study Completion Date: 2024-07-24

Brief Summary

This is an open-label, single center, pharmacokinetic (PK) study to assess valacyclovir pharmacokinetics and pharmacodynamics in neonates and compare to the pharmacokinetics and pharmacodynamics of the standard of care treatment dose of intravenous acyclovir. 6 (up to 10 infants) with virologically confirmed neonatal herpes simplex virus (HSV) disease who meet all inclusion/exclusion criteria will be enrolled in the study. Study duration is 5 years. Primary objective is to define the pharmacokinetics of valacyclovir and assess its safety in neonates 2-12 weeks of age who are ≥ 34 weeks gestation.

Detailed Description

This is an open-label, single center, PK study to assess valacyclovir pharmacokinetics and pharmacodynamics in neonates and compare to the pharmacokinetics and pharmacodynamics of the standard of care treatment dose of intravenous acyclovir. Only those babies with virologically confirmed neonatal HSV disease will be enrolled in the study. The decision to initiate valacyclovir for 2 (up to 7) days will be made by a physician based on inclusion/exclusion criteria, and those who meet entry criteria will be eligible for the study. Those enrolled in the study will have daily random parenteral acyclovir PK levels drawn during the first week of treatment (drawn only at times of other lab draws). These infants will also have a pharmacokinetic sampling profile obtained on or after dose 22 and before dose 42 of intravenous acyclovir. The PK samples for the sampling profile will be collected just prior to the next dose of intravenous acyclovir (within 30 minutes prior to the start of the infusion), within 15 minutes of completion of the infusion, and 3-4 hours after infusion. Upon completion of the recommended treatment course duration with intravenous acyclovir determined by disease classification (skin, eye, and mouth; central nervous system; or disseminated disease), the infant will be started on enteral valacyclovir 20 mg/kg every 8 hours.

On day 2 and no more than day 7 of valacyclovir 20 mg/kg every 8 hours, a pharmacokinetic sampling profile will be obtained. The PK samples will be collected just prior to the enteral dose of valacyclovir (hour 0; 8 hours after previous dose and immediately before next dose), 1-2 hours after dose, and 3-5 hours after dose. Primary objective is to define the pharmacokinetics of valacyclovir and assess its safety in neonates 2-12 weeks of age who are ≥ 34 weeks gestation. Secondary objectives are to: 1) assess the pharmacokinetics of high-dose parenteral acyclovir in neonates ≥ 34 weeks gestation with virologically confirmed neonatal HSV disease who are receiving acyclovir as standard of care, 2) compare the pharmacokinetics of high-dose parenteral acyclovir to the pharmacokinetics of the proposed study dose of valacyclovir (20 mg/kg every 8 hours).

Conditions

Neonatal Herpes Simplex Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Neonatal HSV disease requiring suppressive therapy

All subjects enrolled in the study will receive 2 (up to 7) days of valacyclovir 20 mg/kg every 8 hours after completion of standard of care treatment course with acyclovir.

Group Type: OTHER

Valacyclovir

Intervention Type: DRUG

Upon completion of standard of care acyclovir for treatment of neonatal HSV disease, valacyclovir oral suspension (per ASHP recipe), 20 mg/kg every 8 hours, to be given for 2 (up to 7) days

Interventions

Valacyclovir

Upon completion of standard of care acyclovir for treatment of neonatal HSV disease, valacyclovir oral suspension (per ASHP recipe), 20 mg/kg every 8 hours, to be given for 2 (up to 7) days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed informed consent from parent(s) or legal guardian(s)
• Confirmation of HSV infection from surface culture/PCR, skin lesion culture/PCR, blood PCR, or CSF PCR (performed at UAB Virology lab)
• ≥34 weeks gestational age at birth
• Weight at study enrollment is ≥ 2000 grams
• Receiving intravenous acyclovir, prescribed by the patient's physician for ≤ 14 days
• ≤ 42 days of age at initiation of parenteral acyclovir
• Creatinine ≤ 1.2

Exclusion Criteria

• Imminent demise
• Current receipt of other investigational drugs
• Major congenital anomaly that in the site investigator's opinion may impact drug metabolism or the patient's volume of distribution
• Creatinine of > 1.2 prior to initiation of valacyclovir
• Evidence of immunosuppression (HIV infected, immune deficiencies, etc.)
• Any condition that, in the opinion of the investigator, would place the subject at an unacceptable injury risk or that may interfere with successful study completion
• > 42 days of age at initiation of parenteral acyclovir
• Concern for parental/guardian compliance

• Minimum Eligible Age: 2 Weeks
• Maximum Eligible Age: 12 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Richard J Whitley

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard Whitley, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama - Children's of Alabama

Birmingham, Alabama, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

311653000

Identifier Type: OTHER

Identifier Source: secondary_id

300005567

Identifier Type: -

Identifier Source: org_study_id