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

Herpes Simplex Virus research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Herpes Simplex Virus

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Novel Antiviral Drug4 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.

Drug:Placebo4 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.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Novel Antiviral DrugSubjects 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

PlaceboSubjects 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

Study Status

Withdrawn

Start Date: January 2016

Completed Date: June 2017

Phase: Phase 1/Phase 2

Type: Interventional

Design:

Primary Outcome: Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.

Secondary Outcome: 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

Study sponsors, principal investigator, and references

Principal Investigator: David W Kimberlin, MD

Lead Sponsor: University of Alabama at Birmingham

Collaborator:

More information:https://clinicaltrials.gov/show/NCT01610765

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