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

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ClinicalTrials.gov Identifier: NCT01649869
Recruitment Status : Recruiting
First Posted : July 25, 2012
Last Update Posted : June 8, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
Cytomegalovirus Infection Other: Placebo Drug: Valganciclovir Phase 2

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.

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
Actual Study Start Date : February 24, 2015
Estimated Primary Completion Date : July 27, 2019
Estimated Study Completion Date : February 1, 2020


Arm Intervention/treatment
Active Comparator: Active
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
Drug: Valganciclovir
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.

Placebo Comparator: Placebo
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
Other: Placebo
Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks




Primary Outcome Measures :
  1. Change in total ear hearing assessments (improved + no change versus other) [ Time Frame: From Day 1 through Day 180 ]

Secondary Outcome Measures :
  1. Change in best ear hearing assessments (improved + no change (normal to normal) versus other) [ Time Frame: From Day 1 through Day 180 ]
  2. Change in best ear hearing assessments (improved versus other) [ Time Frame: From Day 1 through Day 180 ]
  3. Change in best ear hearing assessments (worse + no change (abnormal to abnormal)) versus other [ Time Frame: From Day 1 through Day 180 ]
  4. Change in best ear hearing assessments (worse versus other) [ Time Frame: From Day 1 through Day 180 ]
  5. Change in total ear hearing assessments (improved versus other) [ Time Frame: From Day 1 through Day 180 ]
  6. Change in total ear hearing assessments (worse + no change (abnormal to abnormal)) versus other [ Time Frame: From Day 1 through Day 180 ]
  7. Change in total ear hearing assessments (worse versus other) [ Time Frame: From Day 1 through Day 180 ]
  8. Correlation of change in viral load with change in best ear hearing [ Time Frame: Day 180 ]
  9. Correlation of change in viral load with change in total ear hearing [ Time Frame: Day 180 ]
  10. Detection of CMV in saliva by PCR [ Time Frame: Day 180 ]
  11. Detection of CMV in saliva by PCR [ Time Frame: Day 42 ]
  12. Detection of viremia by PCR [ Time Frame: Day 180 ]
  13. Detection of viremia by PCR [ Time Frame: Day 42 ]
  14. Detection of viruria by PCR [ Time Frame: Day 180 ]
  15. Detection of viruria by PCR [ Time Frame: Day 42 ]
  16. Incidence of adverse events which lead to an unresolved outcome [ Time Frame: Up to Day 57 ]
  17. Incidence of adverse events which lead to permanent discontinuation of valganciclovir therapy [ Time Frame: Up to Day 42 ]
  18. Incidence of unanticipated medically attended visits [ Time Frame: From Day 1 through Day 56 ]
  19. The quantitative log reduction in CMV viral load in saliva [ Time Frame: Day 42 ]
  20. The quantitative log reduction in viremia [ Time Frame: Day 42 ]
  21. The quantitative log reduction in viruria [ Time Frame: Day 42 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 4 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


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


Contacts
Contact: David W Kimberlin 12059345316 dkimberlin@peds.uab.edu

Locations
United States, Alabama
University of Alabama - Children's of Alabama - Clinical Virology Recruiting
Birmingham, Alabama, United States, 35233-1711
United States, District of Columbia
Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease Not yet recruiting
Washington, District of Columbia, United States, 20010-2916
United States, Maryland
Johns Hopkins Children's Center - Pediatric Infectious Diseases Not yet recruiting
Baltimore, Maryland, United States, 21287-0011
United States, Missouri
Washington University School of Medicine in St. Louis - Center for Clinical Studies Not yet recruiting
Saint Louis, Missouri, United States, 63110-1010
United States, New York
Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease Not yet recruiting
Manhasset, New York, United States, 11030-3816
University of Rochester Medical Center - Golisano Children's Hospital - Infectious Diseases Not yet recruiting
Rochester, New York, United States, 14642-0001
United States, North Carolina
Carolinas Medical Center - Pediatrics - Infectious Diseases Not yet recruiting
Charlotte, North Carolina, United States, 28203-5812
United States, Ohio
Nationwide Children's Hospital - Neonatology - Center for Perinatal Research Not yet recruiting
Columbus, Ohio, United States, 43205-2664
United States, Rhode Island
Rhode Island Hospital - Pediatrics Not yet recruiting
Providence, Rhode Island, United States, 02903-4923
United States, Texas
Texas Medical Center - Texas Children's Hospital Not yet recruiting
Houston, Texas, United States, 77030
United States, Utah
University of Utah Heath Care - University Hospital - Pediatrics - Infectious Disease Not yet recruiting
Salt Lake City, Utah, United States, 84132-0001
University of Utah - Infectious Diseases Not yet recruiting
Salt Lake City, Utah, United States, 84132-0002
United Kingdom
Bristol Royal Hospital for Children - Paediatric Immunology Not yet recruiting
Bristol, Bristol, City Of, United Kingdom, BS2 8BJ
University College London - Royal Free Campus - Virology Not yet recruiting
London, London, City Of, United Kingdom, NW3 2PF
Saint George's Hospital - Pediatric Infectious Diseases Not yet recruiting
London, London, City Of, United Kingdom, SW17 0QT
Great Ormond Street Hospital - Infectious Diseases Not yet recruiting
London, London, City Of, United Kingdom, WC1N 3JH
Birmingham Heartlands Hospital Not yet recruiting
Birmingham, United Kingdom, B9 5SS
Pennine Acute Hospitals NHS Trust, North Manchester General Hospital - Children's and Adolescent Services Not yet recruiting
Crumpsall, United Kingdom, M8 5RB
John Radcliffe Hospital - Children's Hospital - Paediatric Infectious Disease and Immunology Not yet recruiting
Headington, Oxford, United Kingdom, OX3 9DU
The Great North Children's Hospital - Paediatric Immunology Not yet recruiting
Newcastle Upon Tyne, United Kingdom, NE14LP
Sheffield Children's Hospital - Immunology Not yet recruiting
Sheffield, United Kingdom, S10 2TH
Southampton Children's Hospital - Allergy, Immunology and Infection Not yet recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01649869     History of Changes
Other Study ID Numbers: 11-0069
HHSN272201100035C
First Posted: July 25, 2012    Key Record Dates
Last Update Posted: June 8, 2018
Last Verified: March 22, 2018

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

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
CMV
Cytomegalovirus
Hearing Loss
Infants
Valganciclovir

Additional relevant MeSH terms:
Hearing Loss
Deafness
Infection
Communicable Diseases
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
Valganciclovir
Ganciclovir
Antiviral Agents
Anti-Infective Agents