A Phase 1 interventional study of Valacyclovir in Herpes Simplex, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 12 sites in United States. Open to participants aged 1 Day to 2 Days. Per ClinicalTrials.gov, last updated 2026-07-23.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Prevention
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.
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.
166 studies on the registry are indexed under Herpes Simplex; 12 are open to participants now.
This study's enrollment of 17 is below the median of 66 across 113 interventional studies indexed under Herpes Simplex.
Browse Herpes Simplex studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
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Weight at study enrollment >/= 2,000 grams
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
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
Valacyclovir is a L-valyl ester of acyclovir.
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.
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 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.
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
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.
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
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.
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
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.
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
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.
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)
The number of participants who experienced at least one Grade 3 AE, including both non-serious AEs and serious adverse events (SAEs).
Time frame: 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.
Time frame: Day 1 through Day 42
The study population included neonates delivered to mothers receiving oral valacyclovir therapy (or equivalent antiviral drug) for suppression of genital herpes simplex virus (HSV) recurrences at the end of pregnancy and were within the first two days of life. Participants were enrolled from three sites in the United States between August 7, 2023 and June 4, 2025.
| Milestone | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Started | 15 | 2 |
| Completed | 11 | 2 |
| Not completed | 4 | 0 |
| Withdrew: Lost to follow-up | 2 | 0 |
| Withdrew: Enrolled but treatment not administered | 1 | 0 |
| Withdrew: Voluntary withdrawal by participant's parent/guardian | 1 | 0 |
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.
| mg*h/L | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC12) of Acyclovir in Plasma | 21.18 ± 21.66 | 44.10 ± 47.18 |
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.
| h | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Apparent Terminal Elimination Half-life (t1/2) of Acyclovir in Plasma | 3.72 ± 33.51 | 3.65 ± 0.52 |
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.
| ng/mL | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Maximum Concentration (Cmax) of Acyclovir in Plasma | 3037.47 ± 14.30 | 5911.12 ± 46.15 |
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.
| L/h | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Apparent Oral Clearance (CL/F) of Acyclovir in Plasma | 1.41 ± 25.63 | 1.42 ± 52.14 |
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.
| h | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Time to the Maximum Concentration (Tmax) of Acyclovir in Plasma | 1.77 (1.00 to 4.17) | 4.23 (4.13 to 4.32) |
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.
| L | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Apparent Volume of Distribution During Terminal Phase (V/F) of Acyclovir in Plasma | 7.59 ± 35.14 | 7.47 ± 51.69 |
The number of participants who experienced at least one Grade 3 AE, including both non-serious AEs and serious adverse events (SAEs).
| Participants | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Frequency of Grade 3 Adverse Events (AEs) | 1 | 0 |
The number of participants who experienced at least one Grade 4 AE, including both non-serious AEs and SAEs.
| Participants | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| Frequency of Grade 4 AEs | 0 | 0 |
Collected over All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1: 10 mg/kg Valacyclovir | 0/13 (0%) | 1/13 (7.7%) | 6/13 (46.2%) |
| Cohort 2: 20 mg/kg Valacyclovir | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) |
| Event | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| DehydrationMetabolism and nutrition disorders | 1/13 | 0/2 |
| Event | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir |
|---|---|---|
| White blood cell count decreasedInvestigations | 3/13 | 0/2 |
| VomitingGastrointestinal disorders | 1/13 | 0/2 |
| Blood bilirubin increasedInvestigations | 1/13 | 0/2 |
| Neutrophil count decreasedInvestigations | 1/13 | 0/2 |
| IrritabilityPsychiatric disorders | 1/13 | 0/2 |
| Nasal congestionRespiratory, thoracic and mediastinal disorders | 1/13 | 0/2 |
| HaemorrhageVascular disorders | 1/13 | 0/2 |
| Age, Continuous(days) | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir | Total |
|---|---|---|---|
| Mean | 1.5 ± 0.5 | 1.5 ± 0.7 | 1.5 ± 0.5 |
| Sex: Female, Male(Participants) | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir | Total |
|---|---|---|---|
| Female | 4 | 0 | 4 |
| Male | 11 | 2 | 13 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir | Total |
|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 |
| Not Hispanic or Latino | 14 | 2 | 16 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 9 | 1 | 10 |
| White | 5 | 1 | 6 |
| More than one race | 1 | 0 | 1 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Weight at Enrollment(kg) | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir | Total |
|---|---|---|---|
| Mean | 3.160 ± 0.303 | 3.165 ± 0.177 | 3.161 ± 0.287 |
| Length at Enrollment(cm) | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir | Total |
|---|---|---|---|
| Mean | 51.030 ± 1.381 | 49.750 ± 0.354 | 50.879 ± 1.363 |
| Gestational Age at Birth(weeks) | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir | Total |
|---|---|---|---|
| Mean | 39.1 ± 0.5 | 38.5 ± 0.7 | 39.0 ± 0.5 |
| Weight at Birth(kg) | Cohort 1: 10 mg/kg Valacyclovir | Cohort 2: 20 mg/kg Valacyclovir | Total |
|---|---|---|---|
| Mean | 3.249 ± 0.325 | 3.230 ± 0.269 | 3.247 ± 0.312 |
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Studies of the drug tested here: Valacyclovir
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