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

July 20, 2012
February 17, 2014
March 2014
May 2017   (final data collection date for primary outcome measure)
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 ]
The proportion of children whose sensorineural hearing deteriorates from baseline [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01649869 on ClinicalTrials.gov Archive Site
  • 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 ]
  • The proportion of children who have viruria detected by PCR [ Time Frame: 6 weeks and six months after trial entry ] [ 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 ]
Not Provided
Not Provided
 
Investigation of Six Weeks of Oral Valganciclovir Therapy in Infants and Children With Congenital Cytomegalovirus 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

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Congenital Cytomegalovirus
  • Hearing Loss
  • Drug: Valcyte (Valganciclovir hydrochloride) Powder for oral solution
    Valganciclovir will be administered at 16mg/kg body weight twice daily
  • Drug: Placebo
    The placebo comparator will be commercially available Simple Syrup as 60-90% sucrose.
  • Active Comparator: Valganciclovir
    Intervention: Drug: Valcyte (Valganciclovir hydrochloride) Powder for oral solution
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
54
May 2017
May 2017   (final data collection date for primary outcome measure)

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.
Both
1 Month to 48 Months
No
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,   United Kingdom
 
NCT01649869
DMID 11-0069
Yes
David Kimberlin, MD, University of Alabama at Birmingham
University of Alabama at Birmingham
Not Provided
Principal Investigator: David W Kimberlin, MD University of Alabama at Birmingham
Principal Investigator: Richard Whitley, MD University of Alabama at Birmingham
University of Alabama at Birmingham
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP