Valganciclovir in Congenital CMV Infants
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cytomegalovirus Infections
Intervention: Valganciclovir (Drug); Ganciclovir (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Summary
The purpose of this study is to evaluate how ganciclovir is metabolized when administered
intravenously (by a needle inserted into a vein) following valganciclovir syrup, given by
mouth to newborns and young infants with symptoms of congenital (present at birth)
cytomegalovirus (CMV) disease. The study also seeks to identify a dose of valganciclovir
that provides a comparable blood concentration to ganciclovir present in the blood of
newborns with symptomatic congenital CMV disease. All study participants will receive 6
weeks of antiviral therapy (defined as ganciclovir and/or valganciclovir). Infants from 0 to
30 days old will participate in the study for 2 years.
Clinical Details
Official title: A Phase I/II Pharmacokinetic and Pharmacodynamic Evaluation of Oral Valganciclovir in Neonates With Symptomatic Congenital Cytomegalovirus (CMV) Infection (CASG 109)
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis.
Secondary outcome: Pharmacokinetics of valganciclovir following administration of oral valganciclovir syrup.Lack of vomiting and/or diarrhea associated with administration of oral valganciclovir syrup. Correlation of ganciclovir plasma concentrations following administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood viral load. Assessment of toxicity, such as neutropenia, associated with the administration of oral valganciclovir syrup.
Detailed description:
Recent trials have demonstrated that ganciclovir treatment of neonates with symptomatic
congenital cytomegalovirus (CMV) disease involving the central nervous system results in
improved hearing function (or maintenance of normal hearing function) and prevents hearing
deterioration at 6 months. Furthermore, ganciclovir therapy may prevent hearing
deterioration at 1 year. Ganciclovir recipients also have a more rapid resolution of their
transaminase elevations and a greater degree of short term growth in weight and head
circumference compared with untreated patients. Valganciclovir, the oral product of
ganciclovir, has been developed as a syrup formulation and presents the opportunity to treat
longer, but pharmacokinetic data are needed in infants first to assure the correct dose is
being utilized. This Phase I/II, multi-center, open-label trial will assess the
safety/tolerability and pharmacokinetics (ganciclovir concentrations) following
administration of oral valganciclovir to neonates with symptomatic congenital CMV disease. A
total of 24 patients will be evaluated. All patients entered into this study will receive 6
weeks (42 days) of antiviral therapy (defined as ganciclovir and/or valganciclovir). Two
different dose determination strategies will be applied in this protocol. The first is an
individual patient approach. The second is a group dose modification strategy. The primary
endpoint is pharmacokinetics of ganciclovir following administration of oral valganciclovir
syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis.
Secondary endpoints are: the pharmacokinetics of valganciclovir following administration of
oral valganciclovir; the correlation of ganciclovir plasma concentrations following
administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood
viral load; lack of vomiting and/or diarrhea associated with the administration of oral
valganciclovir syrup; and assessment of toxicity, such as neutropenia, associated with the
administration of oral valganciclovir syrup.
Eligibility
Minimum age: N/A.
Maximum age: 30 Days.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Signed informed consent from parent(s) or legal guardian(s).
- Culture confirmation of cytomegalovirus (CMV) from urine or throat swab specimens.
- Symptomatic congenital CMV disease, as manifest by one or more of the following:
Thrombocytopenia Petechiae Hepatomegaly Splenomegaly Intrauterine growth restriction
Hepatitis (elevated transaminases and/or bilirubin) Central nervous system involvement of
the CMV disease (such as microcephaly, radiographic abnormalities indicative of CMV CNS
disease, abnormal CSF indices for age, chorioretinitis, hearing deficits as detected by
brainstem evoked response, and/or positive CMV PCR from CSF)
- Less than or equal to 30 days of age at study enrollment.
- Weight at study enrollment greater than or equal to 1800 grams.
- Gestational age greater than or equal to 32 weeks.
Exclusion Criteria:
- Imminent demise.
- Patients receiving other antiviral agents or immune globulin.
- Gastrointestinal abnormality which might preclude absorption of an oral medication
(e. g., a history of necrotizing enterocolitis).
- Creatinine clearance < 10mL/min/1. 73 square meters at time of study enrollment.
- Infants known to be born to women who are HIV positive (but HIV testing is not
required for study entry).
Locations and Contacts
University of Alabama at Birmingham, Birmingham, Alabama 35233, United States
University of Arkansas, Little Rock, Arkansas 72202-3591, United States
University of Southern California, Los Angeles, California 90033, United States
Children's Hospital of Orange County, Orange, California 92868, United States
Stanford University, Stanford, California 94305, United States
University of Florida, Jacksonville, Florida 32209, United States
Stroger Cook Hospital, Chicago, Illinois 60612, United States
University of Louisville, Louisville, Kentucky 40202-3830, United States
Tulane University, New Orleans, Louisiana 70112, United States
Johns Hopkins University, Baltimore, Maryland 21287, United States
Washington University in St. Louis, Saint Louis, Missouri 63110, United States
Creighton University, Omaha, Nebraska 68198-2162, United States
Schneider Children's Hospital, Manhasset, New York 11030, United States
SUNY Upstate Medical University, Syracuse, New York 13210, United States
MetroHealth Medical Center, Cleveland, Ohio 44109-1998, United States
Ohio State University, Columbus, Ohio 43205, United States
Medical University of South Carolina, Charleston, South Carolina 29425, United States
The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, United States
Cook Children's Medical Center, Fort Worth, Texas 76104, United States
The University of Texas Medical Branch, Galveston, Texas 77555, United States
The University of Texas Health Science Center, San Antonio, Texas 78229, United States
Additional Information
Starting date: July 2002
Last updated: February 3, 2011
|