Neonatal Phase 1 Valacyclovir Study

NCT05468619 | Completed Phase 1 FDA Drug

• 2 other identifiers: 20-00335U54AI150225-05
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 12

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.

Conditions

Herpes Simplex

Keywords

Disease; Herpes Simplex Virus; Neonatal; Phase I; Valacyclovir

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Half-life (t1/2) of acyclovir

  Days 1 - 5

• Maximum Serum Concentration (Cmax) of acyclovir

  Days 1 - 5

• Occurrence of Grade 3 Adverse Events (AEs)

  Days 1 - 42

• Occurrence of Grade 4 Adverse Events and Serious Adverse Events

  Days 1 - 42

• Oral Clearance (CL/F) of acyclovir

  Days 1 - 5

Study Arms (2)

Cohort 1

EXPERIMENTAL

A cohort of neonates who are at risk of acquiring neonatal herpes simplex virus disease will receive 10 mg/kg of valacyclovir will be administered orally two times daily for 5 days. N=8

Drug: Valacyclovir

Cohort 2

EXPERIMENTAL

If the safety profile and the drug exposure concentrations in Cohort 1 are acceptable, eight new subjects will be enrolled in Cohort 2. If the mean of observed acyclovir exposures of subjects in Cohort 1 are below 24,000 ngxhr/mL, AND if no Grade 3 or Grade 4 AEs or SAEs are detected in any of the study subjects, then the 8 subjects enrolled in Cohort 2 will receive oral valacyclovir at a dose of 20 mg/kg administered two times daily for 5 days. Alternatively, if the mean of observed acyclovir exposures of subjects in Cohort 1 are above 48,000 ngxhr/mL AND if no Grade 3 or Grade 4 AEs or SAEs are detected in any of the study subjects, then the 8 subjects enrolled in Cohort 2 will receive oral valacyclovir at a dose that has been linearly adjusted downward to target 36,000 ngxh/mL area-under-the-concentration-time curve from 0 to 12 hours (AUC12).

Drug: Valacyclovir

Interventions

Valacyclovir DRUG

Valacyclovir is a L-valyl ester of acyclovir.

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 1 Day - 2 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent from parent(s) or legal guardian(s)
• Maternal history of genital HSV infection
• Maternal receipt of oral acyclovir, valacyclovir, or famciclovir suppressive therapy for \>/= 7 days prior to delivery
• Gestational age \>/= 38 weeks at birth
• \</= 2 days of age at study enrollment\*
• Weight at study enrollment \>/= 2,000 grams
• For purposes of this study, the calendar day of birth is Day of Life 0

You may not qualify if:

• Evidence of neonatal HSV infection
• Evidence of sepsis
• Known renal anomalies or dysfunction
• Maternal genital lesions suspicious for HSV at the time of delivery
• Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry)
• Current receipt in the neonate of acyclovir, ganciclovir, famciclovir, or any investigational drugs

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (12)

Children's of Alabama Child Health Research Unit (CHRU)

Birmingham, Alabama, 35233-0011, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322-1014, United States

Location

University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases

Louisville, Kentucky, 40202, United States

Location

M Health Fairview Masonic Children's Hospital

Minneapolis, Minnesota, 55454, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110-1010, United States

Location

Children's Nebraska

Omaha, Nebraska, 68114-4108, United States

Location

Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease

Queens, New York, 11040, United States

Location

University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases

Rochester, New York, 14642-0001, United States

Location

SUNY Upstate Medical University Hospital - Pediatrics

Syracuse, New York, 13210-2342, United States

Location

Atrium Health ID Consultants & Infusion Care Specialists

Charlotte, North Carolina, 28207, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205-2664, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-3522, United States

Location

MeSH Terms

Conditions

Herpes Simplex; Disease

Interventions

Valacyclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: July 21, 2022
• Study Start: August 7, 2023
• Primary Completion: June 8, 2025
• Study Completion: July 15, 2025
• Last Updated: April 1, 2026

Record last verified: 2025-12-02

Locations

US (12)