Short-Term vs. Long-Term Valganciclovir Therapy for Symptomatic Congenital CMV Infections

• Change in best ear hearing assessments. [ Time Frame: Between baseline and 6 months. ] [ Designated as safety issue: No ]
  

• Neurological impairment utilizing the Bayley Scales of Infant and Toddler Development. [ Time Frame: 12 and 24 months of life. ] [ Designated as safety issue: No ]
  
• Change in best ear hearing assessments. [ Time Frame: Between baseline and 12 months and baseline and 24 months. ] [ Designated as safety issue: No ]
  
• Maximum change in hearing assessments over left and right ears. [ Time Frame: Between baseline and 6, 12, and 24 months. ] [ Designated as safety issue: No ]
  
• Hearing deterioration over left and right ears. [ Time Frame: Between baseline and 6, 12, or 24 months. ] [ Designated as safety issue: No ]
  
• Adverse events which lead to permanent discontinuation of valganciclovir therapy or to irreversible outcome of the adverse event. [ Time Frame: Through study month 7. ] [ Designated as safety issue: Yes ]
  

This study is a multi-center, prospective, international, Phase III, randomized and blinded investigation of 6 weeks versus 6 months of oral valganciclovir therapy in babies with symptomatic congenital cytomegalovirus (CMV) disease. Following enrollment, study subjects will receive 6 weeks of oral valganciclovir. Near the end of the 6-week course, subjects will be randomized in a 1:1 fashion either to continue on valganciclovir to complete 6 months of therapy or to begin a matching placebo to complete the 6 months. Study subjects will be stratified according to whether or not there is central nervous system (CNS) involvement at study entry. During the 6-month treatment period and the 1 month thereafter, study subjects will be followed weekly for 4 weeks, then every other week for 8 weeks, then every month for 4 months. At each of these visits, safety labs will be checked, growth parameters recorded, and adverse events assessed. The dose of study medication will be adjusted for weight gain at each of these study visits. Dose adjustments may also occur as indicated per protocol for neutropenia, thrombocytopenia, or renal impairment. Whole blood will be obtained for CMV viral load at each of these visits as well. Hearing outcomes will be assessed at baseline, 6 months, 12 months and 24 months. Developmental outcomes will be assessed at 12 months and 24 months. Changes in whole blood viral load measurements will be correlated with both hearing and neurologic outcomes. In study subjects with increasing whole blood viral loads during the course of treatment, assessment for antiviral resistance may be undertaken. Post-study surveillance to assess potential incidence of cancer will be conducted for as many subjects as possible. Subjects who can be located will be contacted annually for three years for telephone or clinic questioning about whether subject has been diagnosed with cancer. Safety assessments include: hematology labs, chemistry labs, physical examinations, and adverse event data performed/collected serially. Development of neutropenia will be confirmed by repeat blood testing within one week, and study drug will be held until it resolves. Efficacy assessments include: hearing assessments at baseline, 6 months, 12 months and 24 months; and neurodevelopmental assessments at 12 months and 24 months. Study objectives are: to compare the impact on hearing outcomes of 6 weeks versus 6 months of antiviral treatment with valganciclovir oral solution in infants with symptomatic congenital CMV disease; to compare the safety profile of 6 weeks versus 6 months of antiviral therapy with valganciclovir oral solution in infants with symptomatic congenital CMV disease; to compare the impact on neurologic outcomes of 6 weeks versus 6 months of antiviral treatment with valganciclovir oral solution in infants with symptomatic congenital CMV disease; and to correlate change in whole blood viral load with hearing and neurologic outcomes. Participants will include 104 male and female neonates (less than or equal to 30 days) with symptomatic congenital CMV.