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

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ClinicalTrials.gov Identifier: NCT01649869
Recruitment Status : Recruiting
First Posted : July 25, 2012
Last Update Posted : May 25, 2017
Information provided by (Responsible Party):
David Kimberlin, MD, University of Alabama at Birmingham

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.

Condition or disease Intervention/treatment Phase
Congenital Cytomegalovirus Hearing Loss Drug: Valcyte (Valganciclovir hydrochloride) Powder for oral solution Drug: Placebo Phase 2

Detailed Description:

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 whole blood viral loads during the course of treatment, antiviral resistance may be evaluated. A Data and Safety Monitoring Board (DSMB) will be established to oversee the accrual, performance, safety, and efficacy of the trial.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : March 2015
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Arm Intervention/treatment
Active Comparator: Valganciclovir Drug: Valcyte (Valganciclovir hydrochloride) Powder for oral solution
Valganciclovir will be administered at 16mg/kg body weight twice daily
Placebo Comparator: Placebo Drug: Placebo
The placebo comparator will be commercially available Simple Syrup as 60-90% sucrose.

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

Secondary Outcome Measures :
  1. 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 ]
  2. The quantitative log reduction in viruria [ Time Frame: Baseline to end of 6 weeks of therapy ]
  3. The proportion of children who have viremia [ Time Frame: 6 weeks and six months after trial entry ]
  4. The quantitative log reduction in viremia [ Time Frame: Baseline to end of 6 weeks of therapy ]
  5. The proportion of children who have CMV detected in saliva by PCR [ Time Frame: 6 weeks and six months after trial entry ]
  6. The quantitative log reduction in CMV viral load in saliva [ Time Frame: Baseline to end of 6 weeks of therapy ]
  7. The proportion of children whose sensorineural hearing improves or remains unchanged from baseline when measured [ Time Frame: Baseline to 6 months ]
  8. The correlation of change in viral load with change in total ear and best ear hearing [ Time Frame: Baseline to 6 weeks of therapy ]
  9. The change in total ear hearing assessments (improved versus other). [ Time Frame: Baseline to Study Month 6 ]
  10. The proportion of children who have CMV viruria detected by PCR [ Time Frame: 6 weeks and 6 months after trial entry ]
  11. The incidence of unanticipated medically attended visits [ Time Frame: Study Day 1 through 2 weeks following last dose of study drug ]
  12. Incidence of adverse events which lead to permanent discontinuation of valganciclovir therapy or have an unresolved outcome [ Time Frame: baseline through day 42 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 48 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)
  • CMV shedding in urine by PCR or culture (including shell vial) within 12 weeks prior to study enrollment

Exclusion Criteria:•Imminent demise

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01649869

Contact: Bari Cotton, RN 205-934-2424 bcotton@peds.uab.edu
Contact: Penelope M Jester, RN MPH 205-934-2424 pjester@peds.uab.edu

United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: David W Kimberlin, M.D.    205-934-5316    Dkimberlin@peds.uab.edu   
Principal Investigator: David W Kimberlin, M.D.         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, D.C., District of Columbia, United States, 20010
Contact: Roberta L DeBiasi, MD    202-476-5051    rdebiasi@cnmc.org   
Principal Investigator: Roberta L DeBiasi, MD         
United States, Maryland
Johns Hopkins Medical Institutions Recruiting
Baltimore, Maryland, United States, 21287
Contact: Ravit Boger, MD    410-614-3917    boger@jhmi.edu   
Principal Investigator: Ravit Boger, MD         
United States, Missouri
Washington University in St Louis School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Gregory Storch, M.D.    314-454-6079    storch_G@kids.wustl.edu   
Principal Investigator: Gregory Storch, M.D.         
United States, New York
Steven & Alexandra Cohen Children's Medical Center of New York (CCMC) Recruiting
Manhasset, New York, United States, 11030
Contact: Sunil Sood, MD    516-562-3957    sood@lij.edu   
Principal Investigator: Sunil Sood, MD         
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Mary Caserta, M.D.    585-275-5944    mary_caserta@urmc.rochester.edu   
Principal Investigator: Mary Caserta, M.D.         
United States, North Carolina
Carolinas Medical Center - Charlotte Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Amina Ahmed, M.D.B.S.    704-381-6870    Amina.ahmed@carolinashealthcare.org   
Principal Investigator: Amina Ahmed, M.D.B.S.         
United States, Ohio
Nationwide Childrens Hospital Recruiting
Columbus, Ohio, United States, 43205-2664
Contact: Pablo Sanchez, MD    614-355-5724    pablo.sanchez@nationwidechildrens.org   
Principal Investigator: Pablo Sanchez, MD         
United States, Rhode Island
Rhode Island Hospital Recruiting
Providence, Rhode Island, United States, 02903
Contact: Penelope Dennehy, MD    401-444-8360    pdennehy@lifespan.org   
Principal Investigator: Penelope Dennehy, MD         
United Kingdom
Heart of England NHS Foundation Trust Recruiting
Birmingham, England, United Kingdom, B9 5SS
Contact: Scott Hackett, BSc, MD, MB ChB, MRCP, DTM&H    +44 121 424 2696    scott.hackett@heartofengland.nhs.uk   
Principal Investigator: Scott Hackett, BSc, MD, MB ChB, MRCP, DTM&H         
University Hospitals Bristol NHS Foundation Trust Recruiting
Bristal, England, United Kingdom, BS2 8AE
Contact: Stefania Vergnano    44 (0) 117 342 7534    stefanoia.vergnano@UHBristol.nhs.uk   
Principal Investigator: Stafania Vergnano         
Royal Free London NHS Foundation Trust Not yet recruiting
London, England, United Kingdom, NW3 2PF
Contact: Paul Griffiths, M.D.    020-7830-2997    pgriffiths@ucl.ac.uk   
Principal Investigator: Paul Griffiths, M.D.         
Newcastle Upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle Upon Tyne, England, United Kingdom, NE4 6BE
Contact: Marieke Elmonts    0 191 282 5234    marieke.emonts@nuth.nhs.uk   
Principal Investigator: Marieke Elmonts         
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Contact: Saul N Faust    023 8079 4989    s.faust@soton.ac.uk   
Principal Investigator: Saul N Faust         
St. George's University Hospitals NHS Foundation Trust Recruiting
Tooting, London, United Kingdom, SW17 0QT
Contact: Mike Sharland, MBBS MD    +44 20 8725 3262    mike.sharland@stgeorges.nhs.uk   
Principal Investigator: Mike Sharland, MBBS MD         
The Pennine Acute Hospitals NHS Trust Recruiting
Manchester, M8 5rb, United Kingdom
Contact: Paddy McMaster    +44 (0) 161 922 3880    paddy.mcmaster@pat.nhs.uk   
Principal Investigator: Paddy McMaster         
Oxford University Hospitals NHS Trust Recruiting
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Contact: Dominic Kelly    44 (0) 1865 231693    dominic.kelly@paediatrics.ox.ac.uk   
Principal Investigator: Dominic Kelly         
Sheffield Children's NHS FoundationTrust Recruiting
Sheffield, S10 2th, United Kingdom
Contact: Fiona Shackley    +44 (0) 114 271 7172    fiona.shackley@sch.nhs.uk   
Principal Investigator: Fiona Shackley         
Great Ormond Street Hospital for Children NHS Foundation Trust Recruiting
London, United Kingdom, WC1N 3JH
Contact: Nigel Klein, MD    44(0)207-905-2891    n.klein@ucl.ac.uik   
Principal Investigator: Nigel Klein, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
Principal Investigator: David W Kimberlin, MD University of Alabama at Birmingham
Principal Investigator: Richard Whitley, MD University of Alabama at Birmingham

Responsible Party: David Kimberlin, MD, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01649869     History of Changes
Other Study ID Numbers: DMID 11-0069
First Posted: July 25, 2012    Key Record Dates
Last Update Posted: May 25, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
Hearing Loss
Cytomegalovirus Infections
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Antiviral Agents
Anti-Infective Agents