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

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ClinicalTrials.gov Identifier: NCT01610765

Recruitment Status : Withdrawn (Study terminated because unable to obtain access to study drug for study population.)

First Posted : June 4, 2012

Last Update Posted : June 7, 2016

Sponsor:

Information provided by (Responsible Party):

David Kimberlin, MD, University of Alabama at Birmingham

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Herpes Simplex Virus	Drug: Novel Antiviral Drug Drug: Placebo	Phase 1 Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
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 Start Date :	January 2016
Estimated Primary Completion Date :	June 2017
Estimated Study Completion Date :	June 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Herpes Simplex

Genetic and Rare Diseases Information Center resources: Congenital Herpes Simplex Neonatal Herpes

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Novel Antiviral Drug 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	Drug: Novel Antiviral Drug 4 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.
Placebo Comparator: Placebo 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	Drug: Placebo 4 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.

Arm

Intervention/treatment

Active Comparator: Novel Antiviral Drug

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

Drug: Novel Antiviral Drug

4 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.

Placebo Comparator: Placebo

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

Drug: Placebo

4 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.

Outcome Measures

Primary Outcome Measures :

Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease. [ Time Frame: Baseline through day 21 ]
Determine the plasma pharmacokinetics of the CMX001 and cidofovir following administration of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease. [ Time Frame: Baseline through day 21 ]

Secondary Outcome Measures :

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 [ Time Frame: Baseline through day 21 ]
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 [ Time Frame: Baseline through day 56 (end of study) ]

Eligibility Criteria

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Ages Eligible for Study:	up to 98 Days (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01610765

Locations

Show 18 study locations

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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72202
United States, Colorado
University of Colorado at Denver Health Sciences Center
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
University of South Florida School of Medicine
Tampa, Florida, United States, 33606
United States, Georgia
Emory Children's Center
Atlanta, Georgia, United States, 30322
United States, Louisiana
Louisiana State University Health Science Center -Shreveport
Shreveport, Louisiana, United States, 71103
United States, Missouri
Washington University in St Louis School of Medicine
St. Louis, Missouri, United States, 63110
United States, New Hampshire
Dartmouth Medical School
Lebanon, New Hampshire, United States, 03756
United States, New York
Steven & Alexandra Cohen Children's Medical Center Of New York (CCMC)
Manhasset, New York, United States, 11030
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Carolinas Medical Center - Charlotte
Charlotte, North Carolina, United States, 28203
United States, Ohio
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-2581
United States, Texas
University of Texas-Southwestern
Dallas, Texas, United States, 75390-9063
United States, Utah
University of Utah School of Medicine
Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

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Principal Investigator:	David W Kimberlin, MD	University of Alabama at Birmingham
Principal Investigator:	Richard Whitley, MD	University of Alabama at Birmingham

More Information

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Responsible Party:	David Kimberlin, MD, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:	NCT01610765
Other Study ID Numbers:	DMID 11-0068
First Posted:	June 4, 2012 Key Record Dates
Last Update Posted:	June 7, 2016
Last Verified:	June 2016

Keywords provided by David Kimberlin, MD, University of Alabama at Birmingham:


HSV pharmacokinetics herpes neonates

Additional relevant MeSH terms:

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Herpes Simplex Central Nervous System Diseases Virus Diseases Herpesviridae Infections DNA Virus Infections Skin Diseases, Viral	Skin Diseases, Infectious Skin Diseases Nervous System Diseases Antiviral Agents Anti-Infective Agents

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