Assessment of valganciclovir in neonates with CMV

Primary:

-To determine the pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup in neonates and young infants with symptomatic congenital CMV disease

-To identify a dose of valganciclovir to provide comparable ganciclovir plasma concentrations in neonates and young infants with symptomatic congenital CMV disease.

Secondary:

-To evaluate the safety and tolerability of valganciclovir syrup in the neonatal and infantile populations

-To determine the pharmacodynamics of ganciclovir following administration of oral valganciclovir syrup in neonates and young infants with symptomatic congenital CMV disease.

Official Title

A Phase I/II Pharmacokinetic and Pharmacodynamic Evaluation of Oral Valganciclovir in Neonates with Symptomatic Congenital Cytomegalovirus (CMV) Infection Involving the Central Nervous System (CASG 109)

Conditions

– Cytomegalovirus Infections

Study Type

Interventional

Study Design

Treatment, Non-Randomized, Uncontrolled, Crossover Assignment

Further Details

Recent trials have demonstrated that ganciclovir treatment of neonates with symptomatic congenital CMV disease involving the CNS 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 age 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. Ganciclovir therapy must be administered intravenously and often requires the establishment of a central line in these babies. Valganciclovir, the oral prodrug of ganciclovir, has been developed as a syrup formulation and presents the opportunity to treat longer without the requirement for a central line, 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. 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 intravenous ganciclovir or oral valganciclovir syrup with CMV whole blood viral load; the incidence of emesis following oral valganciclovir administration (tolerability); safety as assessed by neutropenia incidence.

Study Start

Eligibility & Criteria

Ages Eligible for Study: up to 1 Month, Genders Eligible for Study: Both Criteria INCLUSION CRITERIA:Signed informed consent from parent(s) or legal guardian(s). Culture confirmation of cytomegalovirus from urine or throat swab specimens. Less than or equal to 30 days of age at study enrollment. Weight at study enrollment > or equal to 1800 grams Gestational age greater than or equal to 32 weeks. – � 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) 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 less than 10 mL/min 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).

Total Enrolment

24

Contact Details

[1] National Institute of Allergy and Infectious Diseases (NIAID) (US)