Valganciclovir Therapy in Infants and Children With Congenital CMV Infection and Hearing Loss

NCT ID: NCT01649869

Last Updated: 2024-10-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-24
• Study Completion Date: 2019-12-24

Brief Summary

This is an international, multi-center, double-blind, placebo-controlled evaluation valganciclovir treatment for up to 54 children (up to 4 years of age) with virologically-confirmed congenital CMV infection and hearing loss. Subject participation will be over a six-month period and study subjects will be stratified according to age. The primary objective is to assess whether a six-week course of oral valganciclovir can stabilize the hearing of children with congenital CMV infection who present with hearing loss.

Detailed Description

Congenital cytomegalovirus (CMV) infection is the most frequent known viral cause of mental retardation, and is the leading non-genetic cause of sensorineural hearing loss in many countries including the United States. This is a Phase II international, multi-center, double-blind, placebo-controlled evaluation of 6 weeks of oral valganciclovir treatment or 6 weeks of placebo for fifty-four male and female infants/toddlers 1 month through 3 years of age (up to 4 years of age) with virologically-confirmed congenital CMV infection and hearing loss. Patient who are between 1 month and 4 years of age and who have SNHL (Sensorineural Hearing Loss) and are eligible for enrollment. The expected study duration is 3.5 years from enrollment of first study subject. The primary objective is to assess whether a six week course of oral valganciclovir can stabilize the hearing of children with congenital CMV infection who present with hearing loss. The secondary objective is to define the following responses as a function of systemic exposure to ganciclovir (active metabolite of valganciclovir): CMV viral load in blood; CMV viral load in urine; and CMV viral load in saliva. Also, to define the safety and tolerability of valganciclovir in enrolled subjects. The tertiary objective is to define the pharmacokinetics of ganciclovir (metabolite) following administration of valganciclovir (prodrug) in enrolled subjects.

Conditions

Cytomegalovirus Infection

Study Design

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

Study Groups

Active

27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive valganciclovir HCl 16.0 mg/kg orally twice a day for 6 weeks

Group Type: ACTIVE_COMPARATOR

Valganciclovir

Intervention Type: DRUG

Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.

Placebo

27 Children between 1 month and 3 years of age (up to 4th birthday) with sensoneural hearing loss and documented CMV infection will receive placebo orally twice a day for 6 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks

Interventions

Placebo

Simple Syrup as 60-90% sucrose in purified water: given orally twice a day for 6 weeks

Intervention Type: OTHER

Valganciclovir

Valcyte (valganciclovir hydrochloride) 50 mg of valganciclovir free base per 1 mL, oral solution: given at 16.0 mg/kg, twice a day for 6 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent from parent(s) or legal guardian(s)

2. Sensorineural hearing loss (>/= 21dB in one or both ears, documented within 12 weeks prior to study entry)

3. Children from 1 month through 3 years of age (up to the 4th birthday)

Exclusion Criteria

1. Imminent demise

2. Profound sensorineural hearing loss (> 90dB) in both ears

3. Patients receiving other antiviral agents or immune globulin

4. Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis)

5. Documented renal insufficiency, as noted by a creatinine clearance < 10 mL/min/1.73m2 at time of study enrollment

6. Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, or maribavir

7. Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry).

8. Current receipt of other investigational drugs

9. Previous receipt of ganciclovir or valganciclovir

10. Known hypersensitivity to ganciclovir, valganciclovir, or components of the product

11. Inability to attend follow-up hearing and clinical assessments

12. Infants with Auditory neuropathy/dyssynchrony.

13. Children with another known etiology for SNHL (e.g. connexin 26, syndrome or metabolic disorder associated with SNHL, inner ear malformation and widened vestibular aqueducts, meningitis).

Exclusion of each of these conditions is not required for trial enrollment.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Children's of Alabama Child Health Research Unit (CHRU)

Birmingham, Alabama, United States

Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease

Washington D.C., District of Columbia, United States

Washington University School of Medicine in St. Louis - Center for Clinical Studies

St Louis, Missouri, United States

Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease

Manhasset, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Carolinas Medical Center - Pediatrics - Infectious Diseases

Charlotte, North Carolina, United States

Nationwide Children's Hospital - Neonatology - Center for Perinatal Research

Columbus, Ohio, United States

Rhode Island Hospital - Pediatrics

Providence, Rhode Island, United States

Texas Medical Center - Texas Children's Hospital

Houston, Texas, United States

Bristol Royal Hospital for Children - Paediatric Immunology

Bristol, Bristol, City of, United Kingdom

Saint George's Hospital - Pediatric Infectious Diseases

London, London, City of, United Kingdom

Great Ormond Street Hospital - Infectious Diseases

London, London, City of, United Kingdom

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Pennine Acute Hospitals NHS Trust, North Manchester General Hospital - Children's and Adolescent Services

Crumpsall, , United Kingdom

John Radcliffe Hospital - Children's Hospital - Paediatric Infectious Disease and Immunology

Headington, Oxford, , United Kingdom

The Great North Children's Hospital - Paediatric Immunology

Newcastle upon Tyne, , United Kingdom

Sheffield Children's Hospital - Immunology

Sheffield, , United Kingdom

Southampton Children's Hospital - Allergy, Immunology and Infection

Southampton, Hampshire, , United Kingdom

Countries

United States; United Kingdom

References

Kimberlin DW, Aban I, Peri K, Nishikawa JK, Bernatoniene J, Emonts M, Klein N, Bamford A, DeBiasi RL, Faust SN, Jones CE, McMaster P, Caserta M, Ahmed A, Sharland M, Demmler-Harrison G, Hackett S, Sanchez PJ, Shackley F, Kelly D, Dennehy PH, Storch GA, Whitley RJ, Griffiths P; Collaborative Antiviral Study Group (CASG). Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial. J Pediatr. 2024 May;268:113934. doi: 10.1016/j.jpeds.2024.113934. Epub 2024 Feb 2.

Reference Type: DERIVED

PMID: 38309519 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

11-0069

Identifier Type: -

Identifier Source: org_study_id