Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants

NCT ID: NCT03107871

Last Updated: 2022-02-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-31
• Study Completion Date: 2024-07-31

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:

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

1. The slope of best ear hearing thresholds over the 20 months after randomization.

2. The MacArthur-Bates Communicative Development Inventory (CDI) percentile score for words produced at 20 months of age.

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.

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.

Conditions

Cmv Congenital; CMV; Congenital Cmv; SNHL; Sensorineural Hearing Loss

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm A

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

Group Type: EXPERIMENTAL

Valganciclovir

Intervention Type: DRUG

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.

Arm B

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

Group Type: PLACEBO_COMPARATOR

Simple Syrup

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Valcyte; Sucrose Water

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.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Deafness and Other Communication Disorders (NIDCD)

NIH

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Albert Park

OTHER

Sponsor Role: lead

Responsible Party

Albert Park

Chief Peds Otolaryngology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Albert Park, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

Lucile Packard Children's Hospital

Palo Alto, California, United States

Rady Children's Hospital - San Diego

San Diego, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Lurie Children's Hospital

Chicago, Illinois, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

Massachusetts Eye and Ear

Boston, Massachusetts, United States

Mott Children's Hospital

Ann Arbor, Michigan, United States

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Saint Louis Universtiy

St Louis, Missouri, United States

Children's Hospital at Dartmouth-Hitchcock

Lebanon, New Hampshire, United States

University of New Mexico

Albuquerque, New Mexico, United States

SUNY Downstate Medical Center

Brooklyn, New York, United States

Weill Cornell Medicine

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Cohen Children's Medical Center

New York, New York, United States

The Children's Hospital at Montefiore

The Bronx, New York, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

UT Southwestern

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Countries

United States

Other Identifiers

1U01DC014706-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

90760

Identifier Type: -

Identifier Source: org_study_id