Valganciclovir Therapy in Infants and Children With Congenital CMV Infection and Hearing Loss
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
1 other identifier
interventional
54
2 countries
18
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2015
Longer than P75 for phase_2
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 20, 2012
CompletedFirst Posted
Study publicly available on registry
July 25, 2012
CompletedStudy Start
First participant enrolled
February 24, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 24, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 24, 2019
CompletedResults Posted
Study results publicly available
June 2, 2021
CompletedOctober 16, 2024
March 22, 2018
4.8 years
July 20, 2012
December 23, 2020
October 11, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Day 1 through Day 180
Secondary Outcomes (25)
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].
Day 1 through Day 180
Change in Best Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
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.
Day 1 through Day 180
Change in Best Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
Day 1 through Day 180
Change in Total Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
Day 1 through Day 180
- +20 more secondary outcomes
Study Arms (2)
Active
ACTIVE COMPARATOR27 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
Placebo
PLACEBO COMPARATOR27 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
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
Children's of Alabama Child Health Research Unit (CHRU)
Birmingham, Alabama, 35233-0011, United States
Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease
Washington D.C., District of Columbia, 20010-2916, United States
Washington University School of Medicine in St. Louis - Center for Clinical Studies
St Louis, Missouri, 63110-1010, United States
Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease
Manhasset, New York, 11030-3816, United States
University of Rochester Medical Center
Rochester, New York, 14642-0001, United States
Carolinas Medical Center - Pediatrics - Infectious Diseases
Charlotte, North Carolina, 28203-5812, United States
Nationwide Children's Hospital - Neonatology - Center for Perinatal Research
Columbus, Ohio, 43205-2664, United States
Rhode Island Hospital - Pediatrics
Providence, Rhode Island, 02903-4923, United States
Texas Medical Center - Texas Children's Hospital
Houston, Texas, 77030, United States
Bristol Royal Hospital for Children - Paediatric Immunology
Bristol, Bristol, City of, BS2 8BJ, United Kingdom
Saint George's Hospital - Pediatric Infectious Diseases
London, London, City of, SW17 0QT, United Kingdom
Great Ormond Street Hospital - Infectious Diseases
London, London, City of, WC1N 3JH, United Kingdom
Birmingham Heartlands Hospital
Birmingham, B9 5SS, United Kingdom
Pennine Acute Hospitals NHS Trust, North Manchester General Hospital - Children's and Adolescent Services
Crumpsall, M8 5RB, United Kingdom
John Radcliffe Hospital - Children's Hospital - Paediatric Infectious Disease and Immunology
Headington, Oxford, OX3 9DU, United Kingdom
The Great North Children's Hospital - Paediatric Immunology
Newcastle upon Tyne, NE14LP, United Kingdom
Sheffield Children's Hospital - Immunology
Sheffield, S10 2TH, United Kingdom
Southampton Children's Hospital - Allergy, Immunology and Infection
Southampton, Hampshire, SO16 6YD, United Kingdom
Related Publications (1)
Kimberlin DW, Aban I, Peri K, Nishikawa JK, Bernatoniene J, Emonts M, Klein N, Bamford A, DeBiasi RL, Faust SN, Jones CE, McMaster P, Caserta M, Ahmed A, Sharland M, Demmler-Harrison G, Hackett S, Sanchez PJ, Shackley F, Kelly D, Dennehy PH, Storch GA, Whitley RJ, Griffiths P; Collaborative Antiviral Study Group (CASG). Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial. J Pediatr. 2024 May;268:113934. doi: 10.1016/j.jpeds.2024.113934. Epub 2024 Feb 2.
PMID: 38309519DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- David Kimberlin, MD
- Organization
- University of Alabama at Birmingham
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 20, 2012
First Posted
July 25, 2012
Study Start
February 24, 2015
Primary Completion
December 24, 2019
Study Completion
December 24, 2019
Last Updated
October 16, 2024
Results First Posted
June 2, 2021
Record last verified: 2018-03-22