Investigation of Six Weeks of Oral Valganciclovir Therapy in Infants and Children With Congenital Cytomegalovirus Infection and Hearing Loss

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by University of Alabama at Birmingham
Sponsor:
Information provided by (Responsible Party):
David Kimberlin, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01649869
First received: July 20, 2012
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Congenital Cytomegalovirus
Hearing Loss
Drug: Valcyte (Valganciclovir hydrochloride) Powder for oral solution
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • The proportion of children whose change in total ear hearing assessments (improved + no change versus other) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]

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

Estimated Enrollment: 54
Study Start Date: March 2014
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   1 Month to 48 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  • CMV shedding in urine by PCR or culture (including shell vial) within 12 weeks prior to study enrollment

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 confirmed etiology for SNHL (e.g. connexin 26, syndrome or metabolic disorder associated with SNHL, inner ear malformation and widened vestibular aqueducts, meningitis). Full exclusion of these conditions is not essential for trial enrollment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01649869

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

Locations
United States, Alabama
University of Alabama at Birmingham Not yet 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 Not yet recruiting
Washington, 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 Not yet 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 Not yet recruiting
St. 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) Not yet 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 Not yet 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 Not yet 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 Not yet 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 Not yet recruiting
Providence, Rhode Island, United States, 02903
Contact: Penelope Dennehy, MD    401-444-8360    pdennehy@lifespan.org   
Principal Investigator: Penelope Dennehy, MD         
United States, Utah
University of Utah School of Medicine Not yet recruiting
Salt Lake City, Utah, United States, 84132
Contact: Kwabena Ampofo, MD    801-581-6791    krow.ampofo@hsc.utah.edu   
Principal Investigator: Kwabena Ampofo, MD         
United Kingdom
Heart of England NHS Foundation Trust Not yet 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 Not yet recruiting
Bristal, England, United Kingdom, BS2 8AE
Contact: Jolanta Bernatoniene    44 (0) 117 342 0172    cdxjb@bristol.ac.uk   
Principal Investigator: Jolanta Bernatoniene         
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 Not yet recruiting
Newcastle Upon Tyne, England, United Kingdom, NE4 6BE
Contact: Sophie Hambleton    0 191 256 3765    sophie.hambleton@newcastle.ac.uk   
Principal Investigator: Sophie Hambleton         
University Hospital Southampton NHS Foundation Trust Not yet 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 Healthcare NHS Trust Not yet 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         
Oxford University Hospitals NHS Trust Not yet recruiting
Oxford, Oxfordshire, United Kingdom, OX3 9DU
Contact: Dominic Kelly    44 (0) 1865 231693    dominic.kelly@paediatrics.ox.ac.uk   
Principal Investigator: Dominic Kelly         
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: David W Kimberlin, MD University of Alabama at Birmingham
Principal Investigator: Richard Whitley, MD University of Alabama at Birmingham
  More Information

No publications provided

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
Study First Received: July 20, 2012
Last Updated: February 17, 2014
Health Authority: United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on July 29, 2014