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

Condition(s) targeted: Herpes Simplex Virus

Intervention: Novel Antiviral Drug (Drug); Placebo (Drug)

Phase: Phase 1/Phase 2

Status: Not yet recruiting

Sponsored by: University of Alabama at Birmingham

Official(s) and/or principal investigator(s):
David W Kimberlin, MD, Principal Investigator, Affiliation: University of Alabama at Birmingham
Richard Whitley, MD, Principal Investigator, Affiliation: University of Alabama at Birmingham

Overall contact:
Penelope M Jester, RN MPH, Phone: 205-934-8559, Email: pjester@peds.uab.edu

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.

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 design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome:

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

Determine the plasma pharmacokinetics of the CMX001 and cidofovir following administration 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

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

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.

Minimum age: N/A. Maximum age: 98 Days. Gender(s): Both.

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

Penelope M Jester, RN MPH, Phone: 205-934-8559, Email: pjester@peds.uab.edu

University of Alabama at Birmingham, Birmingham, Alabama 35233, United States; Not yet recruiting
Bari Cotton, RN, Phone: 205-934-8559, Email: bcotton@peds.uab.edu
Amy Woodall, RN, Phone: 205-934-8559, Email: awoodall@peds.uab.edu
David Kimberlin, MD, Principal Investigator

University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202, United States; Not yet recruiting
Jose Romera, MD, Phone: 501-364-1416, Email: romerojose@uams.edu
Jose Romero, MD, Principal Investigator

University of Colorado at Denver Health Sciences Center, Aurora, Colorado 80045, United States; Not yet recruiting
Mark J Abzug, M.D., Phone: 720-777-6389, Email: abzug.mark@tchden.org
Mark J Abzug, M.D., Principal Investigator

Children's National Medical Center, Washington, District of Columbia 20010, United States; Not yet recruiting
Roberta L Debiasi, MD, Phone: 202-476-5051, Email: rdebiasi@cnmc.org
Roberta L DeBiasi, MD, Principal Investigator

University of South Florida School of Medicine, Tampa, Florida 33606, United States; Not yet recruiting
Jorge Lujan-Zilbermann, MD, Phone: 813-259-8800, Email: jlujanzi@health.usf.edu
Jorge Lujan-Zilbermann, MD, Principal Investigator

Emory Children's Center, Atlanta, Georgia 30322, United States; Not yet recruiting
Andrea Shane, MD MPH, Phone: 404-727-9880, Email: andi_shane@oz.ped.emory.edu
Andrea Shane, MD MPH, Principal Investigator

Louisiana State University Health Science Center -Shreveport, Shreveport, Louisiana 71103, United States; Not yet recruiting
John Vanchiere, MD, PhD, Phone: 318-675-7877, Email: jvanch@lsuhsc.edu
John Vanchiere, MD, PhD, Principal Investigator

Washington University in St Louis School of Medicine, St. Louis, Missouri 63110, United States; Not yet recruiting
Gregory Storch, M.D., Phone: 314-454-6079, Email: storch_G@kids.wustl.edu
Gregory Storch, M.D., Principal Investigator

Dartmouth Medical School, Lebanon, New Hampshire 03756, United States; Not yet recruiting
Peter F Wright, MD, Phone: 603-653-6190, Email: peter.f.wright@dartmouth.edu
Peter F Wright, MD, Principal Investigator

Steven & Alexandra Cohen Children's Medical Center Of New York (CCMC), Manhasset, New York 11030, United States; Not yet recruiting
Sunil Sood, MD, Phone: 516-562-3957, Email: sood@lij.edu
Sunil Sood, MD, Principal Investigator

University of Rochester Medical Center, Rochester, New York 14642, United States; Not yet recruiting
Mary Caserta, M.D., Phone: 585-275-5944, Email: mary_caserta@urmc.rochester.edu
Mary Caserta, M.D., Principal Investigator

Carolinas Medical Center - Charlotte, Charlotte, North Carolina 28203, United States; Not yet recruiting
Amina Ahmed, MD BS, Phone: 704-381-6870, Email: amina.ahmed@carolinashealthcare.org
Amina Ahmed, MD BS, Principal Investigator

MetroHealth Medical Center, Cleveland, Ohio 44109, United States; Not yet recruiting
Nazh F. Abughali, M.D., Phone: 216-778-3402, Email: nabughali@metrohealth.org
Nazha F. Abughali, M.D., Principal Investigator

Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15224, United States; Not yet recruiting
Marian G Michaels, MD, MPH, Phone: 412-692-6786, Email: marian.michaels@chp.edu
Marian G Michaels, MD, MPH, Principal Investigator

Rhode Island Hospital, Providence, Rhode Island 02903, United States; Not yet recruiting
Penelope Dennehy, MD, Phone: 401-444-8360, Email: pdennehy@lifespan.org
Penelope Dennehy, MD, Principal Investigator

Vanderbilt University Medical Center, Nashville, Tennessee 37232-2581, United States; Not yet recruiting
Natasha B Halasa, MD, MPH, Phone: 615-322-3346, Email: natasha.halasa@vanderbilt.edu
Natasha B. Halasa, MD, MPH, Principal Investigator

University of Texas-Southwestern, Dallas, Texas 75390-9063, United States; Not yet recruiting
Pablo Sanchez, MD, Phone: 214-648-3753, Email: Pablo.Sanchez@UTSouthwestern.edu
Pablo Sanchez, MD, Principal Investigator

University of Utah School of Medicine, Salt Lake City, Utah 84132, United States; Not yet recruiting
Kwabena Ampofo, MD, Phone: 801-581-6791, Email: krow.ampofo@hsc.utah.edu
Kwabena Ampofo, MD, Principal Investigator

Starting date: June 2015
Last updated: May 25, 2015