Valganciclovir in Congenital CMV Infants

NCT ID: NCT00031434

Last Updated: 2011-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-07-31
• Study Completion Date: 2007-07-31

Brief 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.

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.

Conditions

Cytomegalovirus Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

All subjects enrolled into this study will receive 6 weeks (42 days) of antiviral therapy (valganciclovir/ganciclovir).

Group Type: EXPERIMENTAL

Valganciclovir

Intervention Type: DRUG

Valganciclovir is a mono-valyl ester pro-drug of ganciclovir, which is rapidly converted to ganciclovir on absorption. Valganciclovir oral syrup formulation for administration will be provided as a 15g powder blend containing 3g valganciclovir base, for constitution in 120 mL amber glass bottles. The beginning oral valganciclovir dose under investigation is 14 mg/kg. The dose of oral valganciclovir syrup will be adjusted for the baby's weight and renal function. Weights upon which dosage will be adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35.

Ganciclovir

Intervention Type: DRUG

Ganciclovir for intravenous infusion will be provided as sterile, lyophilized powder in sealed vials containing 500 mg ganciclovir for re-constitution. The dose of intravenous ganciclovir is 6 mg/kg. Intravenous ganciclovir will be adjusted for the baby's weight and renal function. Weights upon which dosage adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35. Each dose of intravenous ganciclovir should be given over 1 hour using an intravenous pump.

Interventions

Valganciclovir

Valganciclovir is a mono-valyl ester pro-drug of ganciclovir, which is rapidly converted to ganciclovir on absorption. Valganciclovir oral syrup formulation for administration will be provided as a 15g powder blend containing 3g valganciclovir base, for constitution in 120 mL amber glass bottles. The beginning oral valganciclovir dose under investigation is 14 mg/kg. The dose of oral valganciclovir syrup will be adjusted for the baby's weight and renal function. Weights upon which dosage will be adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35.

Intervention Type: DRUG

Ganciclovir

Ganciclovir for intravenous infusion will be provided as sterile, lyophilized powder in sealed vials containing 500 mg ganciclovir for re-constitution. The dose of intravenous ganciclovir is 6 mg/kg. Intravenous ganciclovir will be adjusted for the baby's weight and renal function. Weights upon which dosage adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35. Each dose of intravenous ganciclovir should be given over 1 hour using an intravenous pump.

Intervention Type: DRUG

Eligibility 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).

• Maximum Eligible Age: 30 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

HHS/NIAID/DMID

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arkansas

Little Rock, Arkansas, United States

University of Southern California

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

Stanford University

Stanford, California, United States

University of Florida

Jacksonville, Florida, United States

Stroger Cook Hospital

Chicago, Illinois, United States

University of Louisville

Louisville, Kentucky, United States

Tulane University

New Orleans, Louisiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Washington University in St. Louis

St Louis, Missouri, United States

Creighton University

Omaha, Nebraska, United States

Schneider Children's Hospital

Manhasset, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Medical University of South Carolina

Charleston, South Carolina, United States

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

The University of Texas Medical Branch

Galveston, Texas, United States

The University of Texas Health Science Center

San Antonio, Texas, United States

Countries

United States

Other Identifiers

CASG 109

Identifier Type: -

Identifier Source: secondary_id

01-595

Identifier Type: -

Identifier Source: org_study_id