Investigation of Six Weeks of Oral Valganciclovir Therapy in Infants and Children With Congenital Cytomegalovirus Infection and Hearing Loss

• The proportion of children whose sensorineural hearing deteriorates from baseline [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  

• The proportion of children who have viruria detected by PCR [ Time Frame: 6 weeks and six months after trial entry ] [ Designated as safety issue: No ]
  
• The quantitative log reduction in viruria [ Time Frame: Baseline to end of 6 weeks of therapy ] [ Designated as safety issue: No ]
  
• The proportion of children who have viremia [ Time Frame: 6 weeks and six months after trial entry ] [ Designated as safety issue: No ]
  
• The quantitative log reduction in viremia [ Time Frame: Baseline to end of 6 weeks of therapy ] [ Designated as safety issue: No ]
  
• The proportion of children who have CMV detected in saliva by PCR [ Time Frame: 6 weeks and six months after trial entry ] [ Designated as safety issue: No ]
  
• The quantitative log reduction in CMV viral load in saliva [ Time Frame: Baseline to end of 6 weeks of therapy ] [ Designated as safety issue: No ]
  
• The proportion of children whose sensorineural hearing improves or remains unchanged from baseline when measured [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
  

Upon enrollment, study subjects will be randomized to six weeks of oral valganciclovir or six weeks of oral placebo. Study subjects will be stratified according to age (less than 24 months vs. greater than or equal to 24 months) at study entry. The target number of enrolled evaluable subjects will be 54. Dropouts and subjects with audiology assessments that are inadequate for study comparison will be replaced. During the six week treatment period and the 2 weeks thereafter, study subjects will be followed every 2 weeks. Between Study Day 56 and Study Month 6, study subjects will be followed every 8 weeks (Study Months 4 and 6).

At each of the visits during the treatment phase (Study Days 1, 14, 28, and 42), safety labs will be assessed; viral load specimens from blood, urine, and saliva will be obtained; adverse events will be assessed; and concurrent medications will be recorded. Ganciclovir concentrations for population pharmacokinetic assessment will be obtained at each study visit while the subject is receiving study medication. Dose adjustments for weight change will occur at study visits during the subject's treatment period, and may also occur at any time during the treatment period as indicated per protocol for neutropenia, thrombocytopenia, or renal impairment. At the Study Day 56 visit, safety labs will be obtained; viral load specimens from blood, urine, and saliva will be obtained; and adverse events will be assessed. Hearing will be assessed at baseline and at Study Month 6.

Changes in whole blood viral load measurements will be correlated with hearing outcomes. In study subjects with increasing whole blood viral loads during the course of treatment, antiviral resistance may be evaluated. A Data and Safety Monitoring Board (DSMB) will be established to oversee the accrual, performance, safety, and efficacy of the trial.