Neonatal Herpes Simplex InfectionPhase 1NCT04448392
Valacyclovir in Neonatal Herpes Simplex Virus Disease
A Phase 1 study testing Valacyclovir in people with Neonatal Herpes Simplex Infection, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 12 weeks
- Conditions the study is for
- Neonatal Herpes Simplex Infection
- 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
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2021to 24 Jul 2024
- 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 2 to 12 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama - Children's of Alabama
Birmingham, Alabama, 35233-1711
About this study
Official title: Evaluation of the Pharmacokinetics and Pharmacodynamics of Valacyclovir in Neonates With Neonatal Herpes Simplex Virus Disease Who Have Completed Standard of Care Treatment With Acyclovir
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.
Read the 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
- Being tested
- Valacyclovir
- Keywords
- valacyclovir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValacyclovirDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Valacyclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
This study will determine the blood concentrations of acyclovir flowing valacyclovir administration. The goal is to define the valacyclovir dose which will allow a switch from IV to PO medication. In so doing, the potential duration of hospitalization can be decreased.
To achieve this end, blood is collected to determine AUC.
Measured: 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
This study will determine the blood concentrations of acyclovir flowing valacyclovir administration. The goal is to define the valacyclovir dose which will allow a switch from IV to PO medication. In so doing, the potential duration of hospitalization can be decreased.
To achieve this end, blood is collected to determine T1/2 of drug.
Measured: 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
This study will determine the blood concentrations of acyclovir flowing valacyclovir administration. The goal is to define the valacyclovir dose which will allow a switch from IV to PO medication. In so doing, the potential duration of hospitalization can be decreased.
To achieve this end, blood is collected to determine creatinine clearance of drug.
Measured: 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
To determine if the concentration of the active metabolite acyclovir after administration of acyclovir and valacyclovir at specified time intervals produces the same area under the curve
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start1 Jul 2021
- Primary completion24 Jul 2024
- Study completion24 Jul 2024
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 Neonatal Herpes Simplex InfectionStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard J Whitley, University of Alabama at Birmingham
- Investigators
- Richard Whitley, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04448392
- Sponsor's protocol ID
- 300005567
- Other IDs
- 311653000
- Status last verified
- Jun 2025
- First submitted
- 19 Jun 2020
- Last updated
- 24 Jun 2025
- 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 24 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Pharmacokinetics and Pharmacodynamics of Valacyclovir in Neonates With Neonatal Herpes Simplex Virus Disease Who Have Completed Standard of Care Treatment With Acyclovir
- ClinicalTrials.gov ID
- NCT04448392
- Acronym / sponsor ID
- 300005567
- Conditions
- Neonatal Herpes Simplex Infection
- Keywords
- valacyclovir
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 24 Jul 2024 (actual)
- Study completion
- 24 Jul 2024 (actual)
- First posted
- 25 Jun 2020 (actual)
- Results
- Posted 24 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neonatal HSV disease requiring suppressive therapy | Other | Drug: ValacyclovirAll 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. |
Who may qualify
- Ages
- 2 to 12 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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.)
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 |
|---|---|---|
| ValacyclovirUpon 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 | Drug | Neonatal HSV disease requiring suppressive therapy |
Primary outcome
Area Under the Curve Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours
Time frame: Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours.
Blood will be collected to determine the drug concentration of acyclovir, the metabolite of valacyclovir and will include AUC.
Creatinine Clearance Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours
Time frame: Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours.
Blood will be collected to determine the drug concentration of acyclovir, the metabolite of valacyclovir and will include CL/F.
Half-life Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours
Time frame: Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours.
Blood will be collected to determine the drug concentration of acyclovir, the metabolite of valacyclovir and will include T1/2.
4 secondary outcomes
Area Under the Curve Following Administration of Parenteral Acyclovir 20 mg/kg Every 8 Hours
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2025.
- 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.
Richard Whitley, MD principal investigator
University of Alabama at Birmingham
1 site 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 Neonatal Herpes Simplex Infection, run by University of Alabama at Birmingham at 1 site 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 8 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 24 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 24 Jun 2025). 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 Curve Following Administration of Oral Valacyclovir Suspension 20 mg/kg Every 8 Hours (time frame: Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours.). The study lists 3 primary outcomes in all. 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 24 Jun 2025.