<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04448392</url>
  </required_header>
  <id_info>
    <org_study_id>300005567</org_study_id>
    <nct_id>NCT04448392</nct_id>
  </id_info>
  <brief_title>Valacyclovir in Neonatal Herpes Simplex Virus Disease</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alabama at Birmingham</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, single center, pharmacokinetic (PK) study to assess valacyclovir&#xD;
      pharmacokinetics and pharmacodynamics in neonates and compare to the pharmacokinetics and&#xD;
      pharmacodynamics of the standard of care treatment dose of intravenous acyclovir. 6 (up to 10&#xD;
      infants) with virologically confirmed neonatal herpes simplex virus (HSV) disease who meet&#xD;
      all inclusion/exclusion criteria will be enrolled in the study. Study duration is 5 years.&#xD;
      Primary objective is to define the pharmacokinetics of valacyclovir and assess its safety in&#xD;
      neonates 2-12 weeks of age who are ≥ 34 weeks gestation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, single center, PK study to assess valacyclovir pharmacokinetics and&#xD;
      pharmacodynamics in neonates and compare to the pharmacokinetics and pharmacodynamics of the&#xD;
      standard of care treatment dose of intravenous acyclovir. Only those babies with&#xD;
      virologically confirmed neonatal HSV disease will be enrolled in the study. The decision to&#xD;
      initiate valacyclovir for 2 (up to 7) days will be made by a physician based on&#xD;
      inclusion/exclusion criteria, and those who meet entry criteria will be eligible for the&#xD;
      study. Those enrolled in the study will have daily random parenteral acyclovir PK levels&#xD;
      drawn during the first week of treatment (drawn only at times of other lab draws). These&#xD;
      infants will also have a pharmacokinetic sampling profile obtained on or after dose 22 and&#xD;
      before dose 42 of intravenous acyclovir. The PK samples for the sampling profile will be&#xD;
      collected just prior to the next dose of intravenous acyclovir (within 30 minutes prior to&#xD;
      the start of the infusion), within 15 minutes of completion of the infusion, and 3-4 hours&#xD;
      after infusion. Upon completion of the recommended treatment course duration with intravenous&#xD;
      acyclovir determined by disease classification (skin, eye, and mouth; central nervous system;&#xD;
      or disseminated disease), the infant will be started on enteral valacyclovir 20 mg/kg every 8&#xD;
      hours.&#xD;
&#xD;
      On day 2 and no more than day 7 of valacyclovir 20 mg/kg every 8 hours, a pharmacokinetic&#xD;
      sampling profile will be obtained. The PK samples will be collected just prior to the enteral&#xD;
      dose of valacyclovir (hour 0; 8 hours after previous dose and immediately before next dose),&#xD;
      1-2 hours after dose, and 3-5 hours after dose. Primary objective is to define the&#xD;
      pharmacokinetics of valacyclovir and assess its safety in neonates 2-12 weeks of age who are&#xD;
      ≥ 34 weeks gestation. Secondary objectives are to: 1) assess the pharmacokinetics of&#xD;
      high-dose parenteral acyclovir in neonates ≥ 34 weeks gestation with virologically confirmed&#xD;
      neonatal HSV disease who are receiving acyclovir as standard of care, 2) compare the&#xD;
      pharmacokinetics of high-dose parenteral acyclovir to the pharmacokinetics of the proposed&#xD;
      study dose of valacyclovir (20 mg/kg every 8 hours).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2021</start_date>
  <completion_date type="Anticipated">November 2025</completion_date>
  <primary_completion_date type="Anticipated">October 2025</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the curve following administration of oral valacyclovir suspension 20 mg/kg every 8 hours</measure>
    <time_frame>Between Day 2 and Day 7 of valacyclovir administration: 0, 1-2, 3-5 hours.</time_frame>
    <description>To determine the concentration of the active metabolite acyclovir after administration of valacyclovir at specified time intervals in order to calculate the area under the curve</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the curve following administration of parenteral acyclovir 20 mg/kg every 8 hours</measure>
    <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)</time_frame>
    <description>To determine the concentration of the active metabolite acyclovir after administration of parenteral acyclovir at specified time intervals in order to calculate the area under the curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <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)</time_frame>
    <description>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</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Neonatal Herpes Simplex Infection</condition>
  <arm_group>
    <arm_group_label>Neonatal HSV disease requiring suppressive therapy</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Valacyclovir</intervention_name>
    <description>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</description>
    <arm_group_label>Neonatal HSV disease requiring suppressive therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent from parent(s) or legal guardian(s)&#xD;
&#xD;
          -  Confirmation of HSV infection from surface culture/PCR, skin lesion culture/PCR, blood&#xD;
             PCR, or CSF PCR (performed at UAB Virology lab)&#xD;
&#xD;
          -  ≥34 weeks gestational age at birth&#xD;
&#xD;
          -  Weight at study enrollment is ≥ 2000 grams&#xD;
&#xD;
          -  Receiving intravenous acyclovir, prescribed by the patient's physician for ≤ 14 days&#xD;
&#xD;
          -  ≤ 42 days of age at initiation of parenteral acyclovir&#xD;
&#xD;
          -  Creatinine ≤ 1.2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Imminent demise&#xD;
&#xD;
          -  Current receipt of other investigational drugs&#xD;
&#xD;
          -  Major congenital anomaly that in the site investigator's opinion may impact drug&#xD;
             metabolism or the patient's volume of distribution&#xD;
&#xD;
          -  Creatinine of &gt; 1.2 prior to initiation of valacyclovir&#xD;
&#xD;
          -  Evidence of immunosuppression (HIV infected, immune deficiencies, etc.)&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, would place the subject at an&#xD;
             unacceptable injury risk or that may interfere with successful study completion&#xD;
&#xD;
          -  &gt; 42 days of age at initiation of parenteral acyclovir&#xD;
&#xD;
          -  Concern for parental/guardian compliance&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Weeks</minimum_age>
    <maximum_age>12 Weeks</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Richard Whitley, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Richard Whitley, MD</last_name>
    <phone>205-638-2530</phone>
    <email>rwhitley@peds.uab.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Alabama - Children's of Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233-1711</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Richard Whitley, MD</last_name>
      <phone>205-638-2530</phone>
      <email>rwhitley@peds.uab.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 25, 2020</study_first_posted>
  <last_update_submitted>September 7, 2023</last_update_submitted>
  <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>Richard J Whitley</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>valacyclovir</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Herpes Simplex</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Pregnancy Complications, Infectious</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Valacyclovir</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04448392
org study id: 300005567
nct id: NCT04448392
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
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.
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).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
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.
description: To determine the concentration of the active metabolite acyclovir after administration of valacyclovir at specified time intervals in order to calculate the area under the curve
measure: 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)
description: To determine the concentration of the active metabolite acyclovir after administration of parenteral acyclovir at specified time intervals in order to calculate the area under the curve
measure: 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)
description: 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
arm group label: Neonatal HSV disease requiring suppressive therapy
arm group type: Other
description: 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.
intervention type: Drug
intervention name: Valacyclovir
description: 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
arm group label: Neonatal HSV disease requiring suppressive therapy
criteria: 
gender: All
minimum age: 2 Weeks
maximum age: 12 Weeks
healthy volunteers: No
last name: Richard Whitley, MD
role: Principal Investigator
affiliation: University of Alabama at Birmingham
last name: Richard Whitley, MD
phone: 205-638-2530
email: rwhitley@peds.uab.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: Richard J Whitley
investigator title: Principal Investigator
mesh term: Herpes Simplex
mesh term: Virus Diseases
mesh term: Pregnancy Complications, Infectious
mesh term: Valacyclovir