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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2014 by University of Alabama at Birmingham
Sponsor:
Information provided by (Responsible Party):
David Kimberlin, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01610765
First received: May 30, 2012
Last updated: October 29, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Herpes Simplex Virus
Drug: Novel Antiviral Drug
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 32
Study Start Date: December 2014
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   up to 98 Days
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01610765

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

  Show 18 Study Locations
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: David W Kimberlin, MD University of Alabama at Birmingham
Principal Investigator: Richard Whitley, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: David Kimberlin, MD, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01610765     History of Changes
Other Study ID Numbers: DMID 11-0068
Study First Received: May 30, 2012
Last Updated: October 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
HSV
pharmacokinetics
herpes
neonates

Additional relevant MeSH terms:
Herpes Simplex
DNA Virus Infections
Herpesviridae Infections
Skin Diseases
Skin Diseases, Infectious
Skin Diseases, Viral
Virus Diseases
Antiviral Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014