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Trial record 5 of 101 for:    Valcyte

Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants (ValEAR)

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ClinicalTrials.gov Identifier: NCT03107871
Recruitment Status : Recruiting
First Posted : April 11, 2017
Last Update Posted : July 29, 2019
Sponsor:
Collaborators:
National Institute on Deafness and Other Communication Disorders (NIDCD)
Genentech, Inc.
Information provided by (Responsible Party):
Albert Park, University of Utah

Brief Summary:

The overall goal of this study is to determine the clinical benefit and safety of antiviral therapy for asymptomatic congenital cytomegalovirus (cCMV) infected hearing-impaired infants. We will conduct a multi-center double-blind randomized placebo-controlled trial to determine whether hearing-impaired infants with asymptomatic cCMV have better hearing and language outcomes if they receive valganciclovir antiviral treatment. We will also determine the safety of antiviral valganciclovir therapy for asymptomatic cCMV-infected hearing impaired infants. This study will be unique in that the cohort enrolled will only include hearing-impaired infants with asymptomatic cCMV.

Primary Objective: To determine if treatment of cCMV-infected hearing impaired infants with isolated hearing loss with the antiviral drug valganciclovir reduces the maximum worsening in left or right ear hearing 8 months after randomization compared to untreated cCMV-infected hearing impaired infants.

Main Secondary Objectives:

  1. To determine if valganciclovir treatment improves the following outcomes when compared to the control group:

    1. The risk of a clinically significant worsening of hearing defined by occurrence of cochlear implantation due to progressive hearing loss or a ≥ 10 dB (decibel) increase in the minimum response level (MRL) at two or more audiometric test frequencies (from among 1 kHz, 2 kHz, and 4kHz) in either the left or right ear or a ≥ 15 dB increase at any of these frequencies in either the left or right ear between baseline and 8 months post-randomization.
    2. The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 22 months of age.
    3. The change in the average MRL across the 2 and 4 kHz frequencies from baseline to 8 months post-randomization in the best-ear.
  2. To evaluate safety measures based on all grade 3 or greater new adverse events designated by the NIAID Division of AIDS (DAIDS) toxicity tables.

Condition or disease Intervention/treatment Phase
Cmv Congenital CMV Congenital Cmv SNHL Sensorineural Hearing Loss Drug: Valganciclovir Drug: Simple Syrup Phase 2

Detailed Description:

Cytomegalovirus (CMV) can be transmitted from the mother to the fetus and is a leading cause of sensorineural hearing loss (SNHL), which is a condition where the inner ear is unable to convert sound into nerve impulses to the brain. This hearing loss and its detrimental effect on language development contribute nearly $4 billion annually to the health care costs in the U.S. Unlike other types of SNHL, CMV induced hearing loss can be treated. Several clinical trials have demonstrated that antiviral therapy may prevent progressive hearing loss if administered early in life for severely affected (symptomatic CMV) infants. These promising findings have given rise to a debate regarding the best method for identifying and treating the more numerous asymptomatic CMV-infected infants.

One approach is to conduct universal newborn hearing screens, and then do CMV diagnostic testing only on the infants who fail the hearing screen. This targeted approach should identify those infants at greatest risk of developing progressive hearing loss and consequent communicative difficulties. Utah is the first state to mandate this approach whereby infants under three weeks of age who fail their newborn hearing screening undergo CMV testing. In this trial, the hearing screen targeted approach will be used to identify patients eligible for participation in a double blind placebo controlled randomized clinical trial of antiviral valganciclovir therapy. The results of this trial will inform public policy, potentially shift our current clinical practice regarding pediatric hearing loss evaluation, and potentially offer a therapeutic option to asymptomatic CMV-infected infants with SNHL.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Placebo and active drug will be dispensed in identical amber bottles with identical labeling.
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants: ValEAR Trial
Actual Study Start Date : August 31, 2018
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2024


Arm Intervention/treatment
Experimental: Arm A
Valganciclovir 16 mg/kg PO twice daily (BID) x 6 months
Drug: Valganciclovir
Valganciclovir is supplied as a powder for reconstitution into an oral solution. The reconstituted solution formulation comprises the following excipients: Povidone K30, fumaric acid, sodium benzoate, saccharin sodium, mannitol, flavor, and purified water.
Other Name: Valcyte

Placebo Comparator: Arm B
Flavored Simple Syrup, volume equivalent to active arm dose, PO BID x 6 months
Drug: Simple Syrup
Simple Syrup contains sucrose 85% weight by volume, purified water, and methyl paraben as a preservative along with natural preservatives. It will be flavored to match the flavor of valganciclovir.
Other Name: Sucrose Water




Primary Outcome Measures :
  1. Best-Ear Hearing Score [ Time Frame: Assessed at 8 months post-randomization ]
    The maximum worsening in left or right ear hearing 8 months after randomization compared to untreated cCMV-infected hearing impaired infants will be measured.


Secondary Outcome Measures :
  1. Clinically Significant Worsening of Total-Ear Hearing [ Time Frame: Assessed at 8 months post-randomization ]
    The risk of a clinically significant worsening of hearing defined by occurrence of cochlear implantation due to progressive hearing loss or a ≥ 10 dB increase in the minimum response level (MRL) at two or more audiometric test frequencies (from among 1 kHz, 2 kHz, and 4kHz) in either the left or right ear or a ≥ 15 dB increase at any of these frequencies in either the left or right ear between baseline and 8 months post-randomization.

  2. Communicative Development Outcome [ Time Frame: Assessed at 14 months of age ]
    The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 22 months of age.

  3. Change in Best-Ear Hearing [ Time Frame: Assessed at 8 months post-randomization ]
    The change in the average MRL across the 2 and 4 kHz frequencies from baseline to 8 months post-randomization in the best-ear.


Other Outcome Measures:
  1. Additional hearing endpoints [ Time Frame: Between baseline and the 8 and 20 months post-randomization assessments. ]
    Hearing aid use, cochlear implantation and/or changes in the MRL's at frequencies 1 kHz, 2 kHz, and 4 kHz, between the baseline assessment and the 8 and 20 months post-randomization assessments will be measured.

  2. Communicative development endpoint One [ Time Frame: Assessed at 14 and 22 months of age ]
    Subscales of the MacArthur-Bates CDI will be measured.

  3. Communicative development endpoint Two [ Time Frame: Assessed at 14 and 22 months of age ]
    Scores from the Ages and Stages Questionnaire 3rd edition (ASQ-3) will be measured.

  4. Communicative development endpoint Three [ Time Frame: Assessed at 14 and 22 months of age ]
    The total score from the LittlEARS Auditory Questionnaire will be measured.

  5. Valganciclovir Pharmacokinetics [ Time Frame: From week 2 to month 6 post-randomization ]
    Valganciclovir drug levels will be measured.

  6. Viral Resistance [ Time Frame: Assessed at month 7 post-randomization ]
    The presence of viral resistance will be measured.

  7. Viral Load [ Time Frame: Assessed at baseline month 3, and month 7 post-randomization ]
    Viral load will be measured



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 5 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than or equal to 1 month and less than or equal to 6 months at the time of randomization; AND
  • Positive congenital CMV by urine culture or polymerase chain reaction test(PCR), OR saliva culture or PCR followed by confirmatory urine PCR by 21 days of age, OR urine culture or PCR after 21 days of age followed by newborn dry blood spot PCR; AND
  • Confirmed sensorineural hearing loss (SNHL) by auditory brainstem response (ABR) testing. For ABR assessments, hearing loss is defined as levels greater than 25 dB normal hearing levels (NHL) at 1, 2, or 4 kHz in one or both ears.

Exclusion Criteria:

  • Imminent demise; OR
  • Known hypersensitivity reaction to valganciclovir, ganciclovir, or any components of the investigational product formulation; OR
  • ALT (Alanine Aminotransferase) five times baseline U/L, hepatomegaly, or significant gastrointestinal disorders (e.g., eosinophilic esophagitis, ulcerative colitis); OR
  • Absolute neutrophil count (ANC) less than 500 cells/mm^3, Hemoglobin less than 8 g/dL, or platelets less than 50,000/mm^3, splenomegaly, or significant hematologic disorders (e.g., hemophilia, leukemia, sickle cell anemia); OR
  • Creatinine clearance less than 60 mL/min/1.73m^2 or significant renal disorders (e.g., nephrotic syndrome); OR
  • Potassium greater than 5.5 mEq/L; OR
  • Receiving other antiviral medications or immune globulin therapy; OR
  • Receiving other investigational drugs; OR
  • Breast feeding from a mother receiving antiviral or immunosuppressive medication; OR
  • Known HIV positive mother (risk of immunosuppression); OR
  • Subject is currently using list of prohibited medication specified by the package insert; OR
  • Other known cause contributing to SNHL (e.g., meningitis, aminoglycoside ototoxicity); OR
  • Bilateral profound SNHL or auditory neuropathy spectrum disorder; OR
  • Existing conductive hearing loss or mixed permanent hearing loss is present; OR
  • Evidence of intracranial calcification; OR
  • Evidence of hydrocephalus; OR
  • Microcephaly; OR
  • Presence of petechiae; OR
  • Intrauterine growth retardation; OR
  • Chorioretinitis, optic atrophy or pale optic nerves; OR
  • Parent or guardian unable to speak English or Spanish; OR
  • Subject exposed to a language other than English or Spanish a majority of the time; OR
  • Subject unable to complete hearing assessments or parent/guardian unable to complete communication questionnaires; OR
  • < 32 weeks gestational age at birth; OR
  • Weight at the time of birth < 1800 g.

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): NCT03107871


Contacts
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Contact: Stephanie Dorton, BSN 801-587-7758 stephanie.dorton@hsc.utah.edu
Contact: Kaitlin C Stephens, MBA 801-213-4055 kaitlin.stephens@hsc.utah.edu

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Sponsors and Collaborators
Albert Park
National Institute on Deafness and Other Communication Disorders (NIDCD)
Genentech, Inc.
Investigators
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Principal Investigator: Albert Park, MD University of Utah

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Responsible Party: Albert Park, Chief Peds Otolaryngology, University of Utah
ClinicalTrials.gov Identifier: NCT03107871     History of Changes
Other Study ID Numbers: 90760
1U01DC014706-01A1 ( U.S. NIH Grant/Contract )
First Posted: April 11, 2017    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Albert Park, University of Utah:
valganciclovir

Additional relevant MeSH terms:
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Valganciclovir
Hearing Loss
Hearing Loss, Sensorineural
Deafness
Hearing Disorders
Ear Diseases
Otorhinolaryngologic Diseases
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Antiviral Agents
Anti-Infective Agents