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

Phase 1

Withdrawn

• Conditions: Herpes Simplex Virus
• Interventions: Drug: Placebo; Drug: Novel Antiviral Drug

• Registration Number: NCT01610765
• Lead Sponsor: University of Alabama at Birmingham

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2012-05-30
• Study First Submitted QC: 2012-06-01
• Study First Posted: 2012-06-04
• Study Start: 2016-01
• Status Verified: 2016-06
• Last Update Submitted: 2016-06-06
• Last Update Posted: 2016-06-07
• Primary Completion: 2017-06
• Study Completion: 2017-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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
Novel Antiviral Drug	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

Primary Outcome Measures

Name	Time	Method
Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.	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.	Baseline through day 21

Secondary Outcome Measures

Name	Time	Method
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	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	Baseline through day 56 (end of study)

Trial Locations

Locations (18)

Louisiana State University Health Science Center -Shreveport; 🇺🇸 Shreveport, Louisiana, United States

Washington University in St Louis School of Medicine; 🇺🇸 St. Louis, Missouri, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

University of Colorado at Denver Health Sciences Center; 🇺🇸 Aurora, Colorado, United States

Emory Children's Center; 🇺🇸 Atlanta, Georgia, United States

Dartmouth Medical School; 🇺🇸 Lebanon, New Hampshire, United States

Steven & Alexandra Cohen Children's Medical Center Of New York (CCMC); 🇺🇸 Manhasset, New York, United States

Carolinas Medical Center - Charlotte; 🇺🇸 Charlotte, North Carolina, United States

University of Texas-Southwestern; 🇺🇸 Dallas, Texas, United States

University of Utah School of Medicine; 🇺🇸 Salt Lake City, Utah, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

University of South Florida School of Medicine; 🇺🇸 Tampa, Florida, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States