Clinical Trial: Congenital CMV and Hearing Loss in Children up to 4 Years of Age: Treating With Valganciclovir Therapy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Randomized and Controlled Investigation of Six Weeks of Oral Valganciclovir Therapy in Infants and Children With Congenital Cytomegalovirus Infection and Hearin

Brief Summary:

Valganciclovir is a mono-valyl ester pro-drug of ganciclovir, which is rapidly converted to ganciclovir on absorption. Valganciclovir is approved for the treatment of Cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS), and for the prevention of CMV disease in kidney, heart, and kidney-pancreas high-risk transplant patients. The formulation used in this study will be valganciclovir oral solution which is commercially available. It will be provided as a 12g powder containing 5g valganciclovir free base. The oral solution formulation comprises the following excipients: Providone K30, fumaric acid, sodium benzoate, sodium saccharin, mannitol, flavor, and purified water. The valganciclovir oral solution formulation does not contain lactose anhydrous.

The placebo comparator will be commercially available Simple Syrup (Syrup NF) as 60-90% sucrose in purified water.


Detailed Summary:

Upon enrollment, defined as informed consent signed and confirmed eligibility, study subjects will be randomized, when diagnosis of congenital CMV is confirmed, to six weeks of oral valganciclovir or six weeks of oral placebo. Study subjects will be stratified according to age at randomization (1 through 11 months, 12 through 23 months, 24 through35 months, and greater than or equal to 36 months)and according to country of enrollment (U.S. or U.K.). The sample size of randomized evaluable subjects is 54. Dropouts and subjects with audiology assessments that are inadequate for study comparison will be replaced (up to 20%, or n=10). During the six week treatment period, study subjects will be followed every 2 weeks. Subjects will also be seen at approximately one month following the final dose (Study Day 70), and again at 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 70 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
Sponsor: University of Alabama at Birmingham

Current Primary Outcome: The proportion of children whose change in total ear hearing assessments (improved + no change versus other) [ Time Frame: Baseline to 6 months ]

Original Primary Outcome: The proportion of children whose sensorineural hearing deteriorates from baseline [ Time Frame: Baseline to 6 months ]

Current Secondary Outcome:

  • The proportion of children who have change in best ear hearing assessments [improved + no change (normal to normal) versus other; and worse versus other] [ Time Frame: Baseline to Study Month 6 ]
  • The quantitative log reduction in viruria [ Time Frame: Baseline to end of 6 weeks of therapy ]
  • The proportion of children who have viremia [ Time Frame: 6 weeks and six months after trial entry ]
  • The quantitative log reduction in viremia [ Time Frame: Baseline to end of 6 weeks of therapy ]
  • The proportion of children who have CMV detected in saliva by PCR [ Time Frame: 6 weeks and six months after trial entry ]
  • The quantitative log reduction in CMV viral load in saliva [ Time Frame: Baseline to end of 6 weeks of therapy ]
  • The proportion of children whose sensorineural hearing improves or remains unchanged from baseline when measured [ Time Frame: Baseline to 6 months ]
  • The correlation of change in viral load with change in total ear and best ear hearing [ Time Frame: Baseline to 6 weeks of therapy ]
  • The change in total ear hearing assessments (improved versus other). [ Time Frame: Baseline to Study Month 6 ]
  • The proportion of children who have CMV viruria detected by PCR [ Time Frame: 6 weeks and 6 months after trial entry ]
  • The incidence of unanticipated medically attended visits [ Time Frame: Study Day 1 through 2 weeks following last dose of study drug ]
  • Incidence of adverse events which lead to permanent discontinuation of valganciclovir therapy or have an unresolved outcome [ Time Frame: baseline through day 42 ]


Original Secondary Outcome:

  • The proportion of children who have viruria detected by PCR [ Time Frame: 6 weeks and six months after trial entry ]
  • The quantitative log reduction in viruria [ Time Frame: Baseline to end of 6 weeks of therapy ]
  • The proportion of children who have viremia [ Time Frame: 6 weeks and six months after trial entry ]
  • The quantitative log reduction in viremia [ Time Frame: Baseline to end of 6 weeks of therapy ]
  • The proportion of children who have CMV detected in saliva by PCR [ Time Frame: 6 weeks and six months after trial entry ]
  • The quantitative log reduction in CMV viral load in saliva [ Time Frame: Baseline to end of 6 weeks of therapy ]
  • The proportion of children whose sensorineural hearing improves or remains unchanged from baseline when measured [ Time Frame: Baseline to 6 months ]


Information By: University of Alabama at Birmingham

Dates:
Date Received: July 20, 2012
Date Started: March 2015
Date Completion: May 2017
Last Updated: September 10, 2016
Last Verified: September 2016