search
Back to results

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

Primary Purpose

Cmv Congenital, CMV, Congenital Cmv

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Valganciclovir
Simple Syrup
Sponsored by
Albert Park
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cmv Congenital focused on measuring valganciclovir

Eligibility Criteria

1 Month - 12 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age greater than or equal to 1 month and less than or equal to 12 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
  • 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.

Sites / Locations

  • Lucile Packard Children's Hospital
  • Rady Children's Hospital - San Diego
  • UCSF Benioff Children's Hospital
  • Children's Healthcare of Atlanta
  • Lurie Children's Hospital
  • Indiana University School of Medicine
  • University of Iowa
  • Massachusetts Eye and Ear
  • Mott Children's Hospital
  • University of Minnesota Masonic Children's Hospital
  • Children's Mercy Hospital
  • Saint Louis Universtiy
  • Children's Hospital at Dartmouth-Hitchcock
  • University of New Mexico
  • The Children's Hospital at Montefiore
  • SUNY Downstate Medical Center
  • Weill Cornell Medicine
  • Columbia University Medical Center
  • Cohen Children's Medical Center
  • Nationwide Children's Hospital
  • Oregon Health and Science University
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh
  • Medical University of South Carolina
  • Monroe Carell Jr. Children's Hospital at Vanderbilt
  • UT Southwestern
  • Baylor College of Medicine
  • Primary Children's Hospital
  • Children's Hospital of The King's Daughters
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm A

Arm B

Arm Description

Valganciclovir 16 mg/kg PO twice daily (BID) x 6 months

Flavored Simple Syrup, volume equivalent to active arm dose, PO BID x 6 months

Outcomes

Primary Outcome Measures

Total Ear Hearing Slope
The primary objective of this randomized trial is to determine if treatment of cCMV-infected infants with isolated hearing loss with the antiviral drug valganciclovir reduces the slope of the total ear hearing thresholds over the 20 months after randomization compared to that of untreated cCMV-infected infants with isolated hearing loss.

Secondary Outcome Measures

Best Ear Hearing Slope
The computation of the slope of the best-ear hearing thresholds begins with the same preliminary averaging steps across MRLs and truncation of threshold levels to between 15 and 110 dB as is described above for the total ear hearing slope, but in this case the analysis is based on the best-ear hearing score at each time point.
Percentile Score for Words Produced Endpoint
The main communicative development endpoint will be determined based on the MacArthur-Bates CDI words produced percentile score given at 20 months of age.

Full Information

First Posted
March 13, 2017
Last Updated
February 22, 2022
Sponsor
Albert Park
Collaborators
National Institute on Deafness and Other Communication Disorders (NIDCD), Genentech, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT03107871
Brief Title
Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants
Acronym
ValEAR
Official Title
Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants: ValEAR Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 31, 2018 (Actual)
Primary Completion Date
July 2022 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Albert Park
Collaborators
National Institute on Deafness and Other Communication Disorders (NIDCD), Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 mean slope of total hearing thresholds over the 20 months after randomization compared to untreated cCMV-infected infants with isolated hearing loss. Main Secondary Objectives: To determine if valganciclovir treatment improves the following outcomes when compared to the control group: The slope of best ear hearing thresholds over the 20 months after randomization. The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 20 months of age. To evaluate safety measures based on all grade 3 or greater new adverse events designated by the NIAID Division of AIDS (DAIDS) toxicity tables.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cmv Congenital, CMV, Congenital Cmv, SNHL, Sensorineural Hearing Loss
Keywords
valganciclovir

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Placebo and active drug will be dispensed in identical amber bottles with identical labeling.
Allocation
Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Valganciclovir 16 mg/kg PO twice daily (BID) x 6 months
Arm Title
Arm B
Arm Type
Placebo Comparator
Arm Description
Flavored Simple Syrup, volume equivalent to active arm dose, PO BID x 6 months
Intervention Type
Drug
Intervention Name(s)
Valganciclovir
Other Intervention Name(s)
Valcyte
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Simple Syrup
Other Intervention Name(s)
Sucrose Water
Intervention Description
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.
Primary Outcome Measure Information:
Title
Total Ear Hearing Slope
Description
The primary objective of this randomized trial is to determine if treatment of cCMV-infected infants with isolated hearing loss with the antiviral drug valganciclovir reduces the slope of the total ear hearing thresholds over the 20 months after randomization compared to that of untreated cCMV-infected infants with isolated hearing loss.
Time Frame
Assessed at baseline, 8, 14 and 20 months post-randomization
Secondary Outcome Measure Information:
Title
Best Ear Hearing Slope
Description
The computation of the slope of the best-ear hearing thresholds begins with the same preliminary averaging steps across MRLs and truncation of threshold levels to between 15 and 110 dB as is described above for the total ear hearing slope, but in this case the analysis is based on the best-ear hearing score at each time point.
Time Frame
Assessed at baseline, 8, 14 and 20 months post-randomization
Title
Percentile Score for Words Produced Endpoint
Description
The main communicative development endpoint will be determined based on the MacArthur-Bates CDI words produced percentile score given at 20 months of age.
Time Frame
Assessed at 20 months of age
Other Pre-specified Outcome Measures:
Title
Words Produced Below 10th Percentile
Description
Dichotomous endpoint defined by children's communicative competency as above or below the 10th percentile based upon on the number of words produced.
Time Frame
14 and 20 month of age assessments
Title
Additional MacArthur Bates - Words and Sentences Subscale Percentiles
Description
The percentile scores for the MacArthur Bates Communicative Development Inventory Words and Sentences for complexity and the word form subscales, and the mean length utterance.
Time Frame
20 month of age assessment
Title
MacArthur Bates - Words and Gestures Subscale Percentiles
Description
Secondary communicative development endpoints will be obtained from parent report on the MacArthur Bates Communicative Development Inventory - Words and Gestures form at 14-months. The scores will be the percentile scores for the total number of words produced, total gestures, phrases understood and words understood.
Time Frame
14 months of age assessment
Title
Developmental Domain Endpoints
Description
Based on parent report on the Ages and Stages Questionnaire, 3rd Edition. There are five subtests on the ASQ-3. These include communication, gross motor, fine motor, problem solving, and personal- social. We will use the following scores:1)Raw scores from each subtest 2)Dichotomous endpoints for each subtest based upon the raw score above or below a designated cut-off score based upon age
Time Frame
14 and 20 months of age assessments
Title
Valganciclovir Pharmacokinetics
Description
Valganciclovir drug levels will be measured.
Time Frame
From week 2 to month 6 post-randomization
Title
Viral Resistance
Description
The presence of viral resistance will be measured.
Time Frame
Assessed at month 7 post-randomization
Title
Viral Load
Description
Viral load will be measured
Time Frame
Assessed at baseline month 3, and month 7 post-randomization
Title
LittlEARS
Description
The raw scores will be dichotomized based on the child's hearing age and compared to standardized scores.
Time Frame
14 and 20 months of age assessments

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age greater than or equal to 1 month and less than or equal to 12 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Park, MD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lucile Packard Children's Hospital
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Rady Children's Hospital - San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
UCSF Benioff Children's Hospital
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Lurie Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Massachusetts Eye and Ear
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Minnesota Masonic Children's Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Saint Louis Universtiy
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63103
Country
United States
Facility Name
Children's Hospital at Dartmouth-Hitchcock
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
The Children's Hospital at Montefiore
City
Bronx
State/Province
New York
ZIP/Postal Code
10469
Country
United States
Facility Name
SUNY Downstate Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Cohen Children's Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Monroe Carell Jr. Children's Hospital at Vanderbilt
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
UT Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Children's Hospital of The King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants

We'll reach out to this number within 24 hrs