A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)

A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)

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.

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.

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