Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants

NCT03107871 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 907601U01DC014706-01A1
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 30

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

Conditions

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

Keywords

valganciclovir

Outcome Measures

Primary Outcomes (1)

• 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.

  Assessed at baseline, 8, 14 and 20 months post-randomization

Secondary Outcomes (2)

• Best Ear Hearing Slope

  Assessed at baseline, 8, 14 and 20 months post-randomization

• Percentile Score for Words Produced Endpoint

  Assessed at 20 months of age

Other Outcomes (8)

• Words Produced Below 10th Percentile

  14 and 20 month of age assessments

• Additional MacArthur Bates - Words and Sentences Subscale Percentiles

  20 month of age assessment

• MacArthur Bates - Words and Gestures Subscale Percentiles

  14 months of age assessment

Study Arms (2)

Arm A

EXPERIMENTAL

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

Drug: Valganciclovir

Arm B

PLACEBO COMPARATOR

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

Drug: Simple Syrup

Interventions

Valganciclovir 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.

Also known as: Valcyte

Arm A

Simple Syrup 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.

Also known as: Sucrose Water

Arm B

Eligibility Criteria

• Age: 1 Month - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Albert Park: lead
• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator
• Genentech, Inc.: collaborator

Study Sites (30)

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Massachusetts Eye and Ear

Boston, Massachusetts, 02114, United States

Location

Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, 55455, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Saint Louis Universtiy

St Louis, Missouri, 63103, United States

Location

Children's Hospital at Dartmouth-Hitchcock

Lebanon, New Hampshire, 03756, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cohen Children's Medical Center

New York, New York, 11040, United States

Location

The Children's Hospital at Montefiore

The Bronx, New York, 10469, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

UT Southwestern

Dallas, Texas, 75235, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84132, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Cytomegalovirus Infections; Hearing Loss, Sensorineural

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Albert Park, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo and active drug will be dispensed in identical amber bottles with identical labeling.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Peds Otolaryngology

Study Record Dates

• First Submitted: March 13, 2017
• First Posted: April 11, 2017
• Study Start: August 31, 2018
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2024
• Last Updated: February 24, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (30)