Clinical trial NCT01610765: A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)
Official title: A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Herpes Simplex Virus
Keywords: HSV
pharmacokinetics
herpes
neonates
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2012-06-04
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 98
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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)
* Starting parenteral acyclovir therapy at time of initiation of CMX001 study drug or receiving parenteral acyclovir therapy for ≤ 72 hours before start CMX001 study drug
* ≤ 6 weeks (42 days) of age at time of initial onset of disease symptoms or signs
* Weight at study enrollment ≥ 2,630 grams
* Gestational age ≥ 36 weeks at delivery
* Mother tested negative for HIV during or following pregnancy

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.)
* Birth weight \< 2,500 grams
* Birth weight \> 4,500 grams
* Grade 3 or 4 vomiting, utilizing the DAIDS Toxicity Tables (Appendix B)
* Grade 3 or 4 diarrhea, utilizing the DAIDS Toxicity Tables (Appendix B)
* Creatinine clearance \< 15 mL/min/1.73m2
* Serum albumin \< 2.0 g/dL
* Alanine aminotransferase (ALT) ≥ 2.6-times upper limit normal (ULN)
* Aspartate aminotransferase (AST) ≥ 2.6-times upper limit normal (ULN)
* Direct bilirubin \> 2 mg/dL
* Known immunodeficiency
* Known congenital infection (e.g., symptomatic congenital cytomegalovirus infection; syphilis; congenital toxoplasmosis)
* Congenital heart disease (e.g., patent ductus arteriosus, Tetralogy of Fallot, hypoplastic left heart syndrome, AV canal, VSD, ASD, transposition of the great arteries, hypoplastic right ventricle, truncus arteriosus, pulmonic stenosis, Ebstein anomaly, coarctation of the aorta, interrupted aortic arch, double outlet right ventricle, dilated cardiomyopathy)
* Infants currently receiving or anticipated to need treatment with digoxin that cannot be withheld for the duration of CMX001 therapy
* Infants currently receiving or anticipated to need treatment with ketaconazole that cannot be withheld for the duration of CMX001 therapy
* Receipt of investigation drugs within 30 days prior to enrollment
* Concurrent enrollment or participation in any other interventional research study

Primary outcomes:
measure: Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
timeFrame: Baseline through day 21
measure: Determine the plasma pharmacokinetics of the CMX001 and cidofovir following administration of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
timeFrame: Baseline through day 21
Secondary outcomes:
measure: Explore a plasma drug concentration-response relationship between CMX001 exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy
timeFrame: Baseline through day 21
measure: Explore a plasma drug concentration-response relationship between cidofovir exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy
timeFrame: Baseline through day 56 (end of study)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Aurora
country: United States
facility: University of Colorado at Denver Health Sciences Center
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Shreveport
country: United States
facility: Louisiana State University Health Science Center -Shreveport
state: Louisiana
city: St. Louis
country: United States
facility: Washington University in St Louis School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Medical School
state: New Hampshire
city: Manhasset
country: United States
facility: Steven & Alexandra Cohen Children's Medical Center Of New York (CCMC)
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center - Charlotte
state: North Carolina
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas-Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah School of Medicine
state: Utah
Study officials:
affiliation: University of Alabama at Birmingham
name: David W Kimberlin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Richard Whitley, MD
role: PRINCIPAL_INVESTIGATOR
References: