Valacyclovir in Neonatal Herpes Simplex Virus Disease

NCT04448392 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 300005567311653000
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Neonatal Herpes Simplex Infection

Keywords

valacyclovir

Outcome Measures

Primary Outcomes (3)

• Area Under the Curve Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours

  Blood will be collected to determine the drug concentration of acyclovir, the metabolite of valacyclovir and will include AUC.

  Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours.

• Creatinine Clearance Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours

  Blood will be collected to determine the drug concentration of acyclovir, the metabolite of valacyclovir and will include CL/F.

  Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours.

• Half-life Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours

  Blood will be collected to determine the drug concentration of acyclovir, the metabolite of valacyclovir and will include T1/2.

  Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours.

Secondary Outcomes (4)

• Area Under the Curve Following Administration of Parenteral Acyclovir 20 mg/kg Every 8 Hours

  One PK level drawn randomly on days 1-7; in addition, on one day between day 8 -14 of parenteral acyclovir, 3 PK levels to be drawn (drawn 30 minutes prior to infusion, 15 minutes after completion of infusion, and 3-4 hours after infusion)

• Half-life Following Administration of Parenteral Acyclovir 20 mg/kg Every 8 Hours

  One PK level drawn randomly on days 1-7; in addition, on one day between day 8 -14 of parenteral acyclovir, 3 PK levels to be drawn (drawn 30 minutes prior to infusion, 15 minutes after completion of infusion, and 3-4 hours after infusion)

• Creatinine Clearance Following Administration of Parenteral Acyclovir 20 mg/kg Every 8 Hours

  One PK level drawn randomly on days 1-7; in addition, on one day between day 8 -14 of parenteral acyclovir, 3 PK levels to be drawn (drawn 30 minutes prior to infusion, 15 minutes after completion of infusion, and 3-4 hours after infusion)

• Comparison of the Area Under the Curve of 20 mg/kg IV Acyclovir to the Area Under the Curve of 20 mg/kg PO Valacyclovir

  Random PK levels on days 1-7 of acyclovir administration, PK levels obtained on one day between day 8-14 at specified time intervals, and PK levels obtained one day while on valacyclovir (see outcome 1 and outcome 3 for time intervals)

Study Arms (1)

Neonatal HSV disease requiring suppressive therapy

OTHER

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.

Drug: Valacyclovir

Interventions

Valacyclovir 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

Neonatal HSV disease requiring suppressive therapy

Eligibility Criteria

• Age: 2 Weeks - 12 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama - Children's of Alabama

Birmingham, Alabama, 35233-1711, United States

Location

MeSH Terms

Interventions

Valacyclovir

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Nicole Samies
• Organization: UAB

nsamies2@geisinger.edu

570-271-6440

Study Officials

• Richard Whitley, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 19, 2020
• First Posted: June 25, 2020
• Study Start: July 1, 2021
• Primary Completion: July 24, 2024
• Study Completion: July 24, 2024
• Last Updated: June 24, 2025
• Results First Posted: June 24, 2025

Record last verified: 2025-06

Locations

US (1)