Herpes SimplexPhase 1NCT05468619
Neonatal Phase 1 Valacyclovir Study
A Phase 1 study testing Valacyclovir in people with Herpes Simplex, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 1 day to 2 days
- Conditions the study is for
- Herpes Simplex
- What is being tested?
- Valacyclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 12 sitesUnited States
- Study dates
- 7 Aug 2023to 15 Jul 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 2 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Emory University School of Medicine
Atlanta, Georgia, 30322-1014
Children's of Alabama Child Health Research Unit (CHRU)
Birmingham, Alabama, 35233-0011
Atrium Health ID Consultants & Infusion Care Specialists
Charlotte, North Carolina, 28207
Nationwide Children's Hospital
Columbus, Ohio, 43205-2664
University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases
Louisville, Kentucky, 40202
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226-3522
M Health Fairview Masonic Children's Hospital
Minneapolis, Minnesota, 55454
Children's Nebraska
Omaha, Nebraska, 68114-4108
Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease
Queens, New York, 11040
University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases
Rochester, New York, 14642-0001
Washington University in St. Louis
St Louis, Missouri, 63110-1010
SUNY Upstate Medical University Hospital - Pediatrics
Syracuse, New York, 13210-2342
About this 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
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.
Read the 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.
- Conditions
- Herpes Simplex
- Being tested
- Valacyclovir
- Keywords
- Disease, Herpes Simplex Virus, Neonatal, Phase I, Valacyclovir
- Medical subject headings
- Herpes Simplex, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValacyclovirDrug
Valacyclovir is a L-valyl ester of acyclovir.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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). Receives: Drug: Valacyclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC12) of Acyclovir in Plasma
Pharmacokinetics (PK) parameters were estimated from the Acyclovir plasma concentration-time data after one of the doses received on Study Day 5 (window: Study Day 4 through Study Day 5 around either dose 7, 8, 9, or 10 of the study drug; samples were only collected after one of these doses) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. As blood was only collected up to 8-10 hours post dose, log-linear interpolation was used to calculate the AUC12.
Measured: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Secondary outcomes (7)
Apparent Terminal Elimination Half-life (t1/2) of Acyclovir in Plasma
PK parameters were estimated from the Acyclovir plasma concentration-time data after one of the doses received on Study Day 5 (window: Study Day 4 through Study Day 5 around either dose 7, 8, 9, or 10 of the study drug; samples were only collected after one of these doses) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Measured: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Maximum Concentration (Cmax) of Acyclovir in Plasma
PK parameters were estimated from the Acyclovir plasma concentration-time data after one of the doses received on Study Day 5 (window: Study Day 4 through Study Day 5 around either dose 7, 8, 9, or 10 of the study drug; samples were only collected after one of these doses) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Measured: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Apparent Oral Clearance (CL/F) of Acyclovir in Plasma
PK parameters were estimated from the Acyclovir plasma concentration-time data after one of the doses received on Study Day 5 (window: Study Day 4 through Study Day 5 around either dose 7, 8, 9, or 10 of the study drug; samples were only collected after one of these doses) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Measured: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Time to the Maximum Concentration (Tmax) of Acyclovir in Plasma
PK parameters were estimated from the Acyclovir plasma concentration-time data after one of the doses received on Study Day 5 (window: Study Day 4 through Study Day 5 around either dose 7, 8, 9, or 10 of the study drug; samples were only collected after one of these doses) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Measured: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Apparent Volume of Distribution During Terminal Phase (V/F) of Acyclovir in Plasma
PK parameters were estimated from the Acyclovir plasma concentration-time data after one of the doses received on Study Day 5 (window: Study Day 4 through Study Day 5 around either dose 7, 8, 9, or 10 of the study drug; samples were only collected after one of these doses) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved.
Measured: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Frequency of Grade 3 Adverse Events (AEs)
The number of participants who experienced at least one Grade 3 AE, including both non-serious AEs and serious adverse events (SAEs).
Measured: Day 1 through Day 42
Frequency of Grade 4 AEs
The number of participants who experienced at least one Grade 4 AE, including both non-serious AEs and SAEs.
Measured: Day 1 through Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2022
- Study start7 Aug 2023
- Primary completion8 Jun 2025
- Study completion15 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Herpes SimplexStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05468619
- Sponsor's protocol ID
- 20-0033
- Other IDs
- 5U54AI150225-05
- Status last verified
- 2 Dec 2025
- First submitted
- 19 Jul 2022
- Last updated
- 23 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05468619
- Acronym / sponsor ID
- 20-0033
- Conditions
- Herpes Simplex
- Keywords
- Disease, Herpes Simplex Virus, Neonatal, Phase I, Valacyclovir
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 7 Aug 2023 (actual)
- Primary completion
- 8 Jun 2025 (actual)
- Study completion
- 15 Jul 2025 (actual)
- First posted
- 21 Jul 2022 (actual)
- Results
- Posted 23 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: ValacyclovirA 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 |
| Cohort 2 | Experimental | Drug: ValacyclovirIf 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). |
Who may qualify
- Ages
- 1 day to 2 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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*
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ValacyclovirValacyclovir is a L-valyl ester of acyclovir. | Drug | Cohort 1, Cohort 2 |
Primary outcome
Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC12) of Acyclovir in Plasma
Time frame: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Pharmacokinetics (PK) parameters were estimated from the Acyclovir plasma concentration-time data after one of the doses received on Study Day 5 (window: Study Day 4 through Study Day 5 around either dose 7, 8, 9, or 10 of the study drug; samples were only collected after one of these doses) using Phoenix WinNonlin Non-compartmental analysis. The estimate assumes steady state has been achieved. As blood was only collected up to 8-10 hours post dose, log-linear interpolation was used to calculate the AUC12.
7 secondary outcomes
Apparent Terminal Elimination Half-life (t1/2) of Acyclovir in Plasma
Time frame: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Maximum Concentration (Cmax) of Acyclovir in Plasma
Time frame: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Apparent Oral Clearance (CL/F) of Acyclovir in Plasma
Time frame: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Time to the Maximum Concentration (Tmax) of Acyclovir in Plasma
Time frame: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Apparent Volume of Distribution During Terminal Phase (V/F) of Acyclovir in Plasma
Time frame: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
Frequency of Grade 3 Adverse Events (AEs)
Time frame: Day 1 through Day 42
Frequency of Grade 4 AEs
Time frame: Day 1 through Day 42
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Valacyclovir in people with Herpes Simplex, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC12) of Acyclovir in Plasma (time frame: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.