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

The University of Alabama at Birmingham

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Herpes Simplex Virus

Treatments: Drug: Placebo; Drug: Novel Antiviral Drug

Study type: Interventional

Funder types: Other

Identifiers

NCT01610765

DMID 11-0068

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 1 to 98 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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0 participants in 2 patient groups, including a placebo group

Novel Antiviral Drug

Active Comparator group

Description:

Subjects will be randomized to receive one of 3 oral doses of a Novel Antiviral Drug: 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

Treatment:

Drug: Novel Antiviral Drug

Placebo

Placebo Comparator group

Description:

Subjects will be randomized to receive one of 3 oral doses of placebo matched in volume to active drug: 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

Treatment:

Drug: Placebo