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

NCT01610765 | Withdrawn Phase 1 DMC

• 1 other identifier: DMID 11-0068
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 18

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.

Conditions

Herpes Simplex Virus

Keywords

HSV; pharmacokinetics; herpes; neonates

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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)

Study Arms (2)

Novel Antiviral Drug

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Novel Antiviral Drug 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.

Novel Antiviral Drug

Placebo 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.

Placebo

Eligibility Criteria

• Age: 1 Day - 98 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (18)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72202, United States

Location

University of Colorado at Denver Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of South Florida School of Medicine

Tampa, Florida, 33606, United States

Location

Emory Children's Center

Atlanta, Georgia, 30322, United States

Location

Louisiana State University Health Science Center -Shreveport

Shreveport, Louisiana, 71103, United States

Location

Washington University in St Louis School of Medicine

St Louis, Missouri, 63110, United States

Location

Dartmouth Medical School

Lebanon, New Hampshire, 03756, United States

Location

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

Manhasset, New York, 11030, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Carolinas Medical Center - Charlotte

Charlotte, North Carolina, 28203, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-2581, United States

Location

University of Texas-Southwestern

Dallas, Texas, 75390-9063, United States

Location

University of Utah School of Medicine

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Herpes Simplex

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• David W Kimberlin, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Richard Whitley, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 30, 2012
• First Posted: June 4, 2012
• Study Start: January 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: June 7, 2016

Record last verified: 2016-06

Locations

US (18)