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

NCT ID: NCT01610765

Last Updated: 2016-06-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2017-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Herpes Simplex Virus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Novel Antiviral Drug

Intervention Type 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

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

1 Day

Maximum Eligible Age

98 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

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David Kimberlin, MD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David W Kimberlin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Richard Whitley, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

University of Colorado at Denver Health Sciences Center

Aurora, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

University of South Florida School of Medicine

Tampa, Florida, United States

Site Status

Emory Children's Center

Atlanta, Georgia, United States

Site Status

Louisiana State University Health Science Center -Shreveport

Shreveport, Louisiana, United States

Site Status

Washington University in St Louis School of Medicine

St Louis, Missouri, United States

Site Status

Dartmouth Medical School

Lebanon, New Hampshire, United States

Site Status

Steven & Alexandra Cohen Children's Medical Center Of New York (CCMC)

Manhasset, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Carolinas Medical Center - Charlotte

Charlotte, North Carolina, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Texas-Southwestern

Dallas, Texas, United States

Site Status

University of Utah School of Medicine

Salt Lake City, Utah, United States

Site Status

Countries

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United States

Other Identifiers

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DMID 11-0068

Identifier Type: -

Identifier Source: org_study_id

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