search
Back to results

Valganciclovir Therapy in Infants and Children With Congenital CMV Infection and Hearing Loss

Primary Purpose

Cytomegalovirus Infection

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Valganciclovir
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cytomegalovirus Infection focused on measuring CMV, Cytomegalovirus, Hearing Loss, Infants, Valganciclovir

Eligibility Criteria

1 Month - 4 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed informed consent from parent(s) or legal guardian(s)
  2. Sensorineural hearing loss (>/= 21dB in one or both ears, documented within 12 weeks prior to study entry)
  3. Children from 1 month through 3 years of age (up to the 4th birthday)

Exclusion Criteria:

  1. Imminent demise
  2. Profound sensorineural hearing loss (> 90dB) in both ears
  3. Patients receiving other antiviral agents or immune globulin
  4. Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis)
  5. Documented renal insufficiency, as noted by a creatinine clearance < 10 mL/min/1.73m2 at time of study enrollment
  6. Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribavir
  7. Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry).
  8. Current receipt of other investigational drugs
  9. Previous receipt of ganciclovir or valganciclovir
  10. Known hypersensitivity to ganciclovir, valganciclovir, or components of the product
  11. Inability to attend follow-up hearing and clinical assessments
  12. Infants with Auditory neuropathy/dyssynchrony.
  13. Children with another known etiology for SNHL (e.g. connexin 26, syndrome or metabolic disorder associated with SNHL, inner ear malformation and widened vestibular aqueducts, meningitis).

Exclusion of each of these conditions is not required for trial enrollment.

Sites / Locations

  • University of Alabama - Children's of Alabama - Clinical Virology
  • Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease
  • Washington University School of Medicine in St. Louis - Center for Clinical Studies
  • Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease
  • University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases
  • Carolinas Medical Center - Pediatrics - Infectious Diseases
  • Nationwide Children's Hospital - Neonatology - Center for Perinatal Research
  • Rhode Island Hospital - Pediatrics
  • Texas Medical Center - Texas Children's Hospital
  • Bristol Royal Hospital for Children - Paediatric Immunology
  • Saint George's Hospital - Pediatric Infectious Diseases
  • Great Ormond Street Hospital - Infectious Diseases
  • Birmingham Heartlands Hospital
  • Pennine Acute Hospitals NHS Trust, North Manchester General Hospital - Children's and Adolescent Services
  • John Radcliffe Hospital - Children's Hospital - Paediatric Infectious Disease and Immunology
  • The Great North Children's Hospital - Paediatric Immunology
  • Sheffield Children's Hospital - Immunology
  • Southampton Children's Hospital - Allergy, Immunology and Infection

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active

Placebo

Arm Description

27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks

27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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)
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)
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.
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.
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.

Full Information

First Posted
July 20, 2012
Last Updated
May 6, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
search

1. Study Identification

Unique Protocol Identification Number
NCT01649869
Brief Title
Valganciclovir Therapy in Infants and Children With Congenital CMV Infection and Hearing Loss
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 Hearing Loss
Study Type
Interventional

2. Study Status

Record Verification Date
March 22, 2018
Overall Recruitment Status
Completed
Study Start Date
February 24, 2015 (Actual)
Primary Completion Date
December 24, 2019 (Actual)
Study Completion Date
December 24, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Infection
Keywords
CMV, Cytomegalovirus, Hearing Loss, Infants, Valganciclovir

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active
Arm Type
Active Comparator
Arm Description
27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Valganciclovir
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Ears That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing.
Description
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
Secondary Outcome Measure Information:
Title
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].
Description
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
Title
Change in Best Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
Description
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
Title
Change in Best Ear Hearing Assessments [Worse + no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6.
Description
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
Title
Change in Best Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
Description
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
Title
Change in Total Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
Description
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
Title
Change in Total Ear Hearing Assessments [Worse+ no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6.
Description
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
Title
Change in Total Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
Description
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
Title
Association of Change in Viral Load (Blood) With Change in Total Ear Hearing at 6 Months
Description
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
Title
Association of Change in Viral Load (Saliva) With Change in Total Ear Hearing at 6 Months
Description
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
Title
Association of Change in Viral Load (Urine) With Change in Total Ear Hearing at 6 Months
Description
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
Title
Association of Change in Viral Load (Blood) With Change in Best Ear Hearing at 6 Months
Description
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
Title
Association of Change in Viral Load (Saliva) With Change in Best Ear Hearing at 6 Months
Description
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
Title
Association of Change in Viral Load (Urine) With Change in Best Ear Hearing at 6 Months
Description
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
Title
Detection of Viruria (Urine) by PCR Six Weeks After Trial Entry
Description
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame
At 6 weeks (Day 42)
Title
Detection of Viruria (Urine) by PCR Six Month After Trial Entry
Description
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame
At 6 months
Title
Detection of Viremia (Blood) by PCR Six Weeks After Trial Entry
Description
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame
At 6 weeks (Day 42)
Title
Detection of Viremia (Blood) by PCR Six Month After Trial Entry
Description
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame
At 6 months
Title
Detection of CMV in Saliva by PCR Six Weeks After Trial Entry
Description
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame
At 6 weeks (Day 42)
Title
Detection of CMV in Saliva PCR Six Month After Trial Entry
Description
Each subject either has positive or negative PCR results. Virus is detected if the PCR is positive.
Time Frame
At 6 months
Title
The Quantitative Log Change in Viremia From Baseline to Month 6.
Description
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
Title
The Quantitative Log Reduction in Viruria Detected After 6 Weeks of Therapy
Description
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
Title
The Quantitative Log Reduction in CMV in Saliva Detected After 6 Weeks of Therapy
Description
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
Title
Number of Adverse Events in the Active Group That Resulted in Discontinuation of Valganciclovir
Description
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
Title
Adverse Event (AE) Resulting in Unresolved Outcome
Description
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
Title
Adverse Event (AE) Resulting in Unanticipated Medically Attended Visit
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent from parent(s) or legal guardian(s) Sensorineural hearing loss (>/= 21dB in one or both ears, documented within 12 weeks prior to study entry) Children from 1 month through 3 years of age (up to the 4th birthday) Exclusion Criteria: Imminent demise Profound sensorineural hearing loss (> 90dB) in both ears 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) Documented renal insufficiency, as noted by a creatinine clearance < 10 mL/min/1.73m2 at time of study enrollment Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribavir Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry). Current receipt of other investigational drugs Previous receipt of ganciclovir or valganciclovir Known hypersensitivity to ganciclovir, valganciclovir, or components of the product Inability to attend follow-up hearing and clinical assessments Infants with Auditory neuropathy/dyssynchrony. Children with another known etiology for SNHL (e.g. connexin 26, syndrome or metabolic disorder associated with SNHL, inner ear malformation and widened vestibular aqueducts, meningitis). Exclusion of each of these conditions is not required for trial enrollment.
Facility Information:
Facility Name
University of Alabama - Children's of Alabama - Clinical Virology
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233-1711
Country
United States
Facility Name
Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010-2916
Country
United States
Facility Name
Washington University School of Medicine in St. Louis - Center for Clinical Studies
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110-1010
Country
United States
Facility Name
Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030-3816
Country
United States
Facility Name
University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases
City
Rochester
State/Province
New York
ZIP/Postal Code
14642-0001
Country
United States
Facility Name
Carolinas Medical Center - Pediatrics - Infectious Diseases
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203-5812
Country
United States
Facility Name
Nationwide Children's Hospital - Neonatology - Center for Perinatal Research
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205-2664
Country
United States
Facility Name
Rhode Island Hospital - Pediatrics
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903-4923
Country
United States
Facility Name
Texas Medical Center - Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Bristol Royal Hospital for Children - Paediatric Immunology
City
Bristol
State/Province
Bristol, City Of
ZIP/Postal Code
BS2 8BJ
Country
United Kingdom
Facility Name
Saint George's Hospital - Pediatric Infectious Diseases
City
London
State/Province
London, City Of
ZIP/Postal Code
SW17 0QT
Country
United Kingdom
Facility Name
Great Ormond Street Hospital - Infectious Diseases
City
London
State/Province
London, City Of
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Pennine Acute Hospitals NHS Trust, North Manchester General Hospital - Children's and Adolescent Services
City
Crumpsall
ZIP/Postal Code
M8 5RB
Country
United Kingdom
Facility Name
John Radcliffe Hospital - Children's Hospital - Paediatric Infectious Disease and Immunology
City
Headington, Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Facility Name
The Great North Children's Hospital - Paediatric Immunology
City
Newcastle Upon Tyne
ZIP/Postal Code
NE14LP
Country
United Kingdom
Facility Name
Sheffield Children's Hospital - Immunology
City
Sheffield
ZIP/Postal Code
S10 2TH
Country
United Kingdom
Facility Name
Southampton Children's Hospital - Allergy, Immunology and Infection
City
Southampton, Hampshire
ZIP/Postal Code
SO16 6YD
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Valganciclovir Therapy in Infants and Children With Congenital CMV Infection and Hearing Loss

We'll reach out to this number within 24 hrs