Trial Outcomes & Findings for Neonatal Phase 1 Valacyclovir Study (NCT NCT05468619)
NCT ID: NCT05468619
Last Updated: 2026-07-23
Results Overview
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.
COMPLETED
PHASE1
17 participants
0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 doses
2026-07-23
Participant Flow
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.
Participant milestones
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Overall Study
STARTED
|
15
|
2
|
|
Overall Study
COMPLETED
|
11
|
2
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
Enrolled but treatment not administered
|
1
|
0
|
|
Overall Study
Voluntary withdrawal by participant's parent/guardian
|
1
|
0
|
Baseline Characteristics
Neonatal Phase 1 Valacyclovir Study
Baseline characteristics by cohort
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=15 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
1.5 days
STANDARD_DEVIATION 0.5 • n=9 Participants
|
1.5 days
STANDARD_DEVIATION 0.7 • n=27 Participants
|
1.5 days
STANDARD_DEVIATION 0.5 • n=267 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
4 Participants
n=267 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=9 Participants
|
2 Participants
n=27 Participants
|
13 Participants
n=267 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=267 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
14 Participants
n=9 Participants
|
2 Participants
n=27 Participants
|
16 Participants
n=267 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=9 Participants
|
1 Participants
n=27 Participants
|
10 Participants
n=267 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=9 Participants
|
1 Participants
n=27 Participants
|
6 Participants
n=267 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Weight at Enrollment
|
3.160 kg
STANDARD_DEVIATION 0.303 • n=9 Participants
|
3.165 kg
STANDARD_DEVIATION 0.177 • n=27 Participants
|
3.161 kg
STANDARD_DEVIATION 0.287 • n=267 Participants
|
|
Length at Enrollment
|
51.030 cm
STANDARD_DEVIATION 1.381 • n=9 Participants
|
49.750 cm
STANDARD_DEVIATION 0.354 • n=27 Participants
|
50.879 cm
STANDARD_DEVIATION 1.363 • n=267 Participants
|
|
Gestational Age at Birth
|
39.1 weeks
STANDARD_DEVIATION 0.5 • n=9 Participants
|
38.5 weeks
STANDARD_DEVIATION 0.7 • n=27 Participants
|
39.0 weeks
STANDARD_DEVIATION 0.5 • n=267 Participants
|
|
Weight at Birth
|
3.249 kg
STANDARD_DEVIATION 0.325 • n=9 Participants
|
3.230 kg
STANDARD_DEVIATION 0.269 • n=27 Participants
|
3.247 kg
STANDARD_DEVIATION 0.312 • n=267 Participants
|
PRIMARY outcome
Timeframe: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 dosesPopulation: The PK analysis population includes all participants who successfully complete the scheduled intensive PK sampling procedures and where the primary PK output variable (AUC12) can be determined.
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.
Outcome measures
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=8 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Area Under the Concentration-Time Curve From 0 to 12 Hours (AUC12) of Acyclovir in Plasma
|
21.18 mg*h/L
Geometric Coefficient of Variation 21.66
|
44.10 mg*h/L
Geometric Coefficient of Variation 47.18
|
SECONDARY outcome
Timeframe: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 dosesPopulation: The PK analysis population includes all participants who successfully complete the scheduled intensive PK sampling procedures and where the primary PK output variable (AUC12) can be determined.
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.
Outcome measures
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=8 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Apparent Terminal Elimination Half-life (t1/2) of Acyclovir in Plasma
|
3.72 h
Geometric Coefficient of Variation 33.51
|
3.65 h
Geometric Coefficient of Variation 0.52
|
SECONDARY outcome
Timeframe: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 dosesPopulation: The PK analysis population includes all participants who successfully complete the scheduled intensive PK sampling procedures and where the primary PK output variable (AUC12) can be determined.
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.
Outcome measures
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=8 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Maximum Concentration (Cmax) of Acyclovir in Plasma
|
3037.47 ng/mL
Geometric Coefficient of Variation 14.30
|
5911.12 ng/mL
Geometric Coefficient of Variation 46.15
|
SECONDARY outcome
Timeframe: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 dosesPopulation: The PK analysis population includes all participants who successfully complete the scheduled intensive PK sampling procedures and where the primary PK output variable (AUC12) can be determined.
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.
Outcome measures
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=8 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Apparent Oral Clearance (CL/F) of Acyclovir in Plasma
|
1.41 L/h
Geometric Coefficient of Variation 25.63
|
1.42 L/h
Geometric Coefficient of Variation 52.14
|
SECONDARY outcome
Timeframe: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 dosesPopulation: The PK analysis population includes all participants who successfully complete the scheduled intensive PK sampling procedures and where the primary PK output variable (AUC12) can be determined.
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.
Outcome measures
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=8 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Time to the Maximum Concentration (Tmax) of Acyclovir in Plasma
|
1.77 h
Interval 1.0 to 4.17
|
4.23 h
Interval 4.13 to 4.32
|
SECONDARY outcome
Timeframe: 0 hour minus 15 minutes (pre-dose), 1-2 hours, 4-6 hours, and 8-10 hours post one of the Day 5 dosesPopulation: The PK analysis population includes all participants who successfully complete the scheduled intensive PK sampling procedures and where the primary PK output variable (AUC12) can be determined.
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.
Outcome measures
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=8 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Apparent Volume of Distribution During Terminal Phase (V/F) of Acyclovir in Plasma
|
7.59 L
Geometric Coefficient of Variation 35.14
|
7.47 L
Geometric Coefficient of Variation 51.69
|
SECONDARY outcome
Timeframe: Day 1 through Day 42Population: The Safety Population includes participants who received at least one dose of study product.
The number of participants who experienced at least one Grade 3 AE, including both non-serious AEs and serious adverse events (SAEs).
Outcome measures
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=13 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Frequency of Grade 3 Adverse Events (AEs)
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 42Population: The Safety Population includes participants who received at least one dose of study product.
The number of participants who experienced at least one Grade 4 AE, including both non-serious AEs and SAEs.
Outcome measures
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=13 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 Participants
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Frequency of Grade 4 AEs
|
0 Participants
|
0 Participants
|
Adverse Events
Cohort 1: 10 mg/kg Valacyclovir
Cohort 2: 20 mg/kg Valacyclovir
Serious adverse events
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=13 participants at risk
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 participants at risk
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
7.7%
1/13 • Number of events 1 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
0.00%
0/2 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
Other adverse events
| Measure |
Cohort 1: 10 mg/kg Valacyclovir
n=13 participants at risk
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 10 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
Cohort 2: 20 mg/kg Valacyclovir
n=2 participants at risk
Neonates who were at risk of acquiring neonatal herpes simplex virus disease received 20 mg/kg of valacyclovir administered orally two times daily for 5 days.
|
|---|---|---|
|
Psychiatric disorders
Irritability
|
7.7%
1/13 • Number of events 1 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
0.00%
0/2 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.7%
1/13 • Number of events 1 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
0.00%
0/2 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
|
Vascular disorders
Haemorrhage
|
7.7%
1/13 • Number of events 1 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
0.00%
0/2 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13 • Number of events 1 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
0.00%
0/2 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
|
Investigations
Blood bilirubin increased
|
7.7%
1/13 • Number of events 1 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
0.00%
0/2 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
|
Investigations
Neutrophil count decreased
|
7.7%
1/13 • Number of events 1 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
0.00%
0/2 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
|
Investigations
White blood cell count decreased
|
23.1%
3/13 • Number of events 3 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
0.00%
0/2 • All AEs, including safety laboratory AEs, and all SAEs were documented from Study Day 1 through the final study visit (Study Day 42).
AEs were assessed for participants in the Safety Population, which includes participants who received at least one dose of study product
|
Additional Information
David W. Kimberlin, MD
University of Alabama at Birmingham
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60