A Multiple Ascending Dose-Finding Pharmacokinetic and Pharmacodynamic Study of a Novel Antiviral Drug in Infants With Neonatal Herpes Simplex Virus (HSV) - Full Text View

Purpose

This study is to identify if a Novel Antiviral Drug could be used to treat babies with Herpes Simplex Virus (HSV) with central nervous system (CNS) disease. In this study the investigators will identify the best dose for young children as well as identify additional safety information about the Novel Antiviral Drug.

Condition	Intervention	Phase
Herpes Simplex Virus	Drug: Novel Antiviral Drug Drug: Placebo	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Multiple Ascending Dose-Finding Pharmacokinetic and Pharmacodynamic Study of a Novel Antiviral Drug in Infants With Neonatal Herpes Simplex Virus (HSV)

Resource links provided by NLM:

MedlinePlus related topics: Herpes Simplex

U.S. FDA Resources

Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:

Plasma pharmacokinetic parameters for a Novel Antiviral Drug, including AUC24, maximum serum concentration (Cmax), half-life (T1/2), CL/F, and time to maximum concentration (Tmax) [ Time Frame: From baseline through visit day 21 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clearance of HSV DNA from CSF by Day 4 of antiviral treatment of neonatal HSV disease [ Time Frame: baseline through visit day 21 ] [ Designated as safety issue: No ]
The incidence of SAEs and AEs considered to be related to study treatment [ Time Frame: Baseline through visit day 56 (end of study) ] [ Designated as safety issue: Yes ]
The incidence of grade 3-4 AEs and SAEs, with or without relationship to study treatment [ Time Frame: Baseline through visit day 56 (end of study) ] [ Designated as safety issue: Yes ]
Intracellular pharmacokinetic parameters for the active diphosphate moiety of a Novel Antiviral Drug in peripheral blood mononuclear cells (PBMCs) [ Time Frame: baseline through visit day 21 ] [ Designated as safety issue: No ]
Correlation of a Novel Antiviral Drug plasma and intracellular concentrations with qualitative and quantitative HSV detection in cerebrospinal fluid and blood by PCR [ Time Frame: baseline through visit day 21 ] [ Designated as safety issue: No ]

Estimated Enrollment:	32
Study Start Date:	July 2013
Estimated Study Completion Date:	June 2016
Estimated Primary Completion Date:	June 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Novel Antiviral Drug Subjects will be randomized to receive one of 4 oral doses of a Novel Antiviral Drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered	Drug: Novel Antiviral Drug 4 oral doses of a Novel Antiviral Drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level.
Placebo Comparator: Placebo Subjects will be randomized to receive one of 4 oral doses of placebo matched in volume to active drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered	Drug: Placebo 4 oral doses of placebo matching the a Novel Antiviral Drug assigned dose: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level.

Arms

Assigned Interventions

Active Comparator: Novel Antiviral Drug

Subjects will be randomized to receive one of 4 oral doses of a Novel Antiviral Drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered

Drug: Novel Antiviral Drug

4 oral doses of a Novel Antiviral Drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level.

Placebo Comparator: Placebo

Subjects will be randomized to receive one of 4 oral doses of placebo matched in volume to active drug: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered

Drug: Placebo

4 oral doses of placebo matching the a Novel Antiviral Drug assigned dose: 0.25 mg/kg/dose, 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered. Subjects will be assigned a the higher dose of study drug after the DSMB and sponsor determine that reported adverse events and the PK data show that it is safe to increase dosing to the next higher level.

Detailed Description:

In this study, the pharmacokinetics and safety of a Novel Antiviral Drug will be determined in babies with neonatal HSV CNS disease. The study will be conducted at 18 academic medical centers throughout the United States. Young infants presenting with virologic confirmation of neonatal HSV infection and evidence of CNS involvement will be eligible for study enrollment. Study Day 1 is defined as the day when dose 1 of the Novel Antiviral Drug study medication is administered.

Eligibility

Ages Eligible for Study:	up to 98 Days
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Signed Informed Consent by parent or legal guardian of study subject
Virologically confirmed HSV infection [e.g., positive culture, DNA detection by polymerase chain reaction (PCR), or direct fluorescent antibody stain from any body site or compartment]
Evidence of CNS involvement of HSV disease [e.g., CSF pleocytosis, positive CSF PCR testing, clinical or electroencephalogram (EEG) seizure activity, neuroimaging abnormality)
Receiving or starting parenteral acyclovir therapy
Hospitalized
≤ 6 weeks (42 days) of age at time of initial onset of disease symptoms or signs
Weight at study enrollment ≥ 2,500 grams
Gestational age ≥ 36 weeks at delivery

Exclusion Criteria:

Imminent demise
Disseminated or skin/eye/mouth (SEM) neonatal HSV disease classifications
Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., history of necrotizing enterocolitis, gastroschisis, malrotation, etc.)
Suspicion of significant renal impairment (e.g., polycystic renal disease, renal anomaly, renal agenesis, renal failure, anuria)
Alanine aminotransferase (ALT) ≥ 2-times upper limit normal (ULN)
Total bilirubin ≥ 5-times upper limit normal (ULN)
Infants known to be born to women who are HIV positive (HIV testing is not required for study entry)
Receipt of investigation drugs within 30 days prior to enrollment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610765

Contacts

Contact: Dusty Giles, RN CCRA	205-934-8559	dgiles@peds.uab.edu
Contact: Penelope M Jester, RN MPH	205-934-8559	pjester@peds.uab.edu

Show 18 Study Locations

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

Principal Investigator:	David W Kimberlin, MD	University of Alabama at Birmingham
Principal Investigator:	Richard Whitley, MD	University of Alabama at Birmingham

More Information

No publications provided

Responsible Party:	David Kimberlin, MD, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:	NCT01610765 History of Changes
Other Study ID Numbers:	DMID 11-0068
Study First Received:	May 30, 2012
Last Updated:	March 1, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:

HSV
pharmacokinetics
herpes
neonates

Additional relevant MeSH terms:

Herpes Simplex
Virus Diseases
Herpesviridae Infections
DNA Virus Infections
Skin Diseases, Viral
Skin Diseases, Infectious

Skin Diseases
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013