This is an international, multi-center, double-blind, placebo-controlled evaluation valganciclovir treatment for up to 54 children (up to 4 years of age) with virologically-confirmed congenital CMV infection and hearing loss. Subject participation will be over a six-month period and study subjects will be stratified according to age. The primary objective is to assess whether a six-week course of oral valganciclovir can stabilize the hearing of children with congenital CMV infection who present with hearing loss.
Congenital cytomegalovirus (CMV) infection is the most frequent known viral cause of mental retardation, and is the leading non-genetic cause of sensorineural hearing loss in many countries including the United States. This is a Phase II international, multi-center, double-blind, placebo-controlled evaluation of 6 weeks of oral valganciclovir treatment or 6 weeks of placebo for fifty-four male and female infants/toddlers 1 month through 3 years of age (up to 4 years of age) with virologically-confirmed congenital CMV infection and hearing loss. Patient who are between 1 month and 4 years of age and who have SNHL (Sensorineural Hearing Loss) and are eligible for enrollment. The expected study duration is 3.5 years from enrollment of first study subject. The primary objective is to assess whether a six week course of oral valganciclovir can stabilize the hearing of children with congenital CMV infection who present with hearing loss. The secondary objective is to define the following responses as a function of systemic exposure to ganciclovir (active metabolite of valganciclovir): CMV viral load in blood; CMV viral load in urine; and CMV viral load in saliva. Also, to define the safety and tolerability of valganciclovir in enrolled subjects. The tertiary objective is to define the pharmacokinetics of ganciclovir (metabolite) following administration of valganciclovir (prodrug) in enrolled subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
54
Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks
Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.
Children's of Alabama Child Health Research Unit (CHRU)
Birmingham, Alabama, United States
Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease
Washington D.C., District of Columbia, United States
Washington University School of Medicine in St. Louis - Center for Clinical Studies
St Louis, Missouri, United States
Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease
Manhasset, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Carolinas Medical Center - Pediatrics - Infectious Diseases
Charlotte, North Carolina, United States
Nationwide Children's Hospital - Neonatology - Center for Perinatal Research
Columbus, Ohio, United States
Rhode Island Hospital - Pediatrics
Providence, Rhode Island, United States
Texas Medical Center - Texas Children's Hospital
Houston, Texas, United States
Bristol Royal Hospital for Children - Paediatric Immunology
Bristol, Bristol, City of, United Kingdom
...and 8 more locations
Number of Ears That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing.
A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification will be mild hearing loss. Not both ears are evaluable for all subjects. In some subjects, only one ear is evaluable.
Time frame: Day 1 through Day 180
Number of Best Ear That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing [ex. Improved+ no Change (Normal to Normal) Versus Other].
A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification will be mild hearing loss. For this outcome, we combine the improved hearing and no change for the special case only of normal to normal. Other category include worsened and no change from (1) mild to mild hearing loss, (2) moderate to moderate hearing loss, or (3) severe to severe hearing loss.
Time frame: Day 1 through Day 180
Change in Best Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification will be mild hearing loss.
Time frame: Day 1 through Day 180
Change in Best Ear Hearing Assessments [Worse + no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6.
A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification will be mild hearing loss.
Time frame: Day 1 through Day 180
Change in Best Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification will be mild hearing loss.
Time frame: Day 1 through Day 180
Change in Total Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification will be mild hearing loss.
Time frame: Day 1 through Day 180
Change in Total Ear Hearing Assessments [Worse+ no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6.
A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification will be mild hearing loss.
Time frame: Day 1 through Day 180
Change in Total Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
A single, independent study audiologist who is masked (blinded) to treatment assignment will assess the audiology test battery for each subject and assign the classifications of normal hearing, mild hearing loss, moderate hearing loss, or severe hearing loss based upon their hearing thresholds (in decibels). The classifications will be assigned by ear (one for the left ear and one for the right ear), giving "total ear" classifications. At the analyses stage, the "best ear" classification for the subject at that study visit will be determined; for example, if a subject had mild hearing loss in their left ear and severe hearing loss in their right ear, then the "best ear" classification will be mild hearing loss.
Time frame: Day 1 through Day 180
Association of Change in Viral Load (Blood) With Change in Total Ear Hearing at 6 Months
Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml\*days divided by days in study which equals log 10 copies/ml.
Time frame: At 6 months
Association of Change in Viral Load (Saliva) With Change in Total Ear Hearing at 6 Months
Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units or log 10 copies/ml\*days divided by days in study which equals log 10 copies/ml.
Time frame: At 6 months
Association of Change in Viral Load (Urine) With Change in Total Ear Hearing at 6 Months
Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml\*days divided by days in study which equals log 10 copies/ml.
Time frame: At 6 months
Association of Change in Viral Load (Blood) With Change in Best Ear Hearing at 6 Months
Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml\*days divided by days in study which equals log 10 copies/ml.
Time frame: At 6 months
Association of Change in Viral Load (Saliva) With Change in Best Ear Hearing at 6 Months
Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml\*days divided by days in study which equals log 10 copies/ml.
Time frame: At 6 months
Association of Change in Viral Load (Urine) With Change in Best Ear Hearing at 6 Months
Analysis of actual viral load was done using log base 10 transformation. Undetectable viral load value was replaced by a value of 10. A summary measure of the viral load over time considers all time points available by calculating the average area under the curve (AUC) (trapezoidal rule) applied to the log base 10 viral load. Average is based on the maximum period of time with viral load data for a given subject. The average or standardize AUC units is therefore the original AUC units of log 10 copies/ml\*days divided by days in study which equals log 10 copies/ml.
Time frame: At 6 months
Detection of Viruria (Urine) by PCR Six Weeks After Trial Entry
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time frame: At 6 weeks (Day 42)
Detection of Viruria (Urine) by PCR Six Month After Trial Entry
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time frame: At 6 months
Detection of Viremia (Blood) by PCR Six Weeks After Trial Entry
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time frame: At 6 weeks (Day 42)
Detection of Viremia (Blood) by PCR Six Month After Trial Entry
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time frame: At 6 months
Detection of CMV in Saliva by PCR Six Weeks After Trial Entry
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time frame: At 6 weeks (Day 42)
Detection of CMV in Saliva PCR Six Month After Trial Entry
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time frame: At 6 months
The Quantitative Log Change in Viremia From Baseline to Month 6.
The quantitative change (Month 6 minus baseline) in viremia (blood) Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units).
Time frame: Baseline to month 6
The Quantitative Log Reduction in Viruria Detected After 6 Weeks of Therapy
The quantitative log reduction in viruria (urine) detected after 6 weeks of therapy. Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units)
Time frame: Baseline thru months 6
The Quantitative Log Reduction in CMV in Saliva Detected After 6 Weeks of Therapy
The quantitative log reduction in CMV in saliva (urine) detected after 6 weeks of therapy. Quantitative viral load by PCR in log 10 units measured in urine after 6 weeks of therapy; if undetectable, viral load is assigned a value of 10 (1 in log 10 units)
Time frame: Baseline thru months 6
Number of Adverse Events in the Active Group That Resulted in Discontinuation of Valganciclovir
AE resulting in discontinuation of valganciclovir (active group only). This outcome summarizes the number of adverse events (AEs) that resulted in the discontinuation of valganciclovir in the active group only.
Time frame: Day 1 thru day 70
Adverse Event (AE) Resulting in Unresolved Outcome
Adverse event resulting in unresolved outcome. This outcome summarizes the number of adverse events (AEs) that resulted in unresolved outcome of that AE.
Time frame: Day 1 thru day 70
Adverse Event (AE) Resulting in Unanticipated Medically Attended Visit
Adverse event resulting in unanticipated medically attended visit. This outcome summarizes the number of adverse events (AEs) that resulted in the unanticipated medically attended visit.
Time frame: Day 1 thru day 70
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