Clinical trial NCT01649869: Valganciclovir Therapy in Infants and Children With Congenital CMV Infection and Hearing Loss
Official title: A Phase II Randomized and Controlled Investigation of Six Weeks of Oral Valganciclovir Therapy in Infants and Children With Congenital Cytomegalovirus Infection and Hearing Loss
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus Infection
Keywords: CMV
Cytomegalovirus
Hearing Loss
Infants
Valganciclovir
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2012-07-25
Enrollment: 54
Sex: ALL
Minimum age (years): 1
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Ears That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing.
timeFrame: Day 1 through Day 180
Secondary outcomes:
measure: Number of Best Ear That Had (1) Improved Hearing or no Change in Hearing (2) Worsened Hearing [ex. Improved+ no Change (Normal to Normal) Versus Other].
timeFrame: Day 1 through Day 180
measure: Change in Best Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
timeFrame: Day 1 through Day 180
measure: Change in Best Ear Hearing Assessments [Worse + no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6.
timeFrame: Day 1 through Day 180
measure: Change in Best Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
timeFrame: Day 1 through Day 180
measure: Change in Total Ear Hearing Assessments [Improved Versus Other] Between Baseline and Study Month 6.
timeFrame: Day 1 through Day 180
measure: Change in Total Ear Hearing Assessments [Worse+ no Change (Abnormal to Abnormal) Versus Other] Between Baseline and Study Month 6.
timeFrame: Day 1 through Day 180
measure: Change in Total Ear Hearing Assessments [Worse Versus Other] Between Baseline and Study Month 6.
timeFrame: Day 1 through Day 180
measure: Association of Change in Viral Load (Blood) With Change in Total Ear Hearing at 6 Months
timeFrame: At 6 months
measure: Association of Change in Viral Load (Saliva) With Change in Total Ear Hearing at 6 Months
timeFrame: At 6 months
measure: Association of Change in Viral Load (Urine) With Change in Total Ear Hearing at 6 Months
timeFrame: At 6 months
measure: Association of Change in Viral Load (Blood) With Change in Best Ear Hearing at 6 Months
timeFrame: At 6 months
measure: Association of Change in Viral Load (Saliva) With Change in Best Ear Hearing at 6 Months
timeFrame: At 6 months
measure: Association of Change in Viral Load (Urine) With Change in Best Ear Hearing at 6 Months
timeFrame: At 6 months
measure: Detection of Viruria (Urine) by PCR Six Weeks After Trial Entry
timeFrame: At 6 weeks (Day 42)
measure: Detection of Viruria (Urine) by PCR Six Month After Trial Entry
timeFrame: At 6 months
measure: Detection of Viremia (Blood) by PCR Six Weeks After Trial Entry
timeFrame: At 6 weeks (Day 42)
measure: Detection of Viremia (Blood) by PCR Six Month After Trial Entry
timeFrame: At 6 months
measure: Detection of CMV in Saliva by PCR Six Weeks After Trial Entry
timeFrame: At 6 weeks (Day 42)
measure: Detection of CMV in Saliva PCR Six Month After Trial Entry
timeFrame: At 6 months
measure: The Quantitative Log Change in Viremia From Baseline to Month 6.
timeFrame: Baseline to month 6
measure: The Quantitative Log Reduction in Viruria Detected After 6 Weeks of Therapy
timeFrame: Baseline thru months 6
measure: The Quantitative Log Reduction in CMV in Saliva Detected After 6 Weeks of Therapy
timeFrame: Baseline thru months 6
measure: Number of Adverse Events in the Active Group That Resulted in Discontinuation of Valganciclovir
timeFrame: Day 1 thru day 70
measure: Adverse Event (AE) Resulting in Unresolved Outcome
timeFrame: Day 1 thru day 70
measure: Adverse Event (AE) Resulting in Unanticipated Medically Attended Visit
timeFrame: Day 1 thru day 70
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama Child Health Research Unit (CHRU)
state: Alabama
city: Washington
country: United States
facility: Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease
state: District of Columbia
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis - Center for Clinical Studies
state: Missouri
city: Manhasset
country: United States
facility: Steven and Alexandra Cohen Childrens Medical Center of New York - New Hyde Park - Infectious Disease
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center - Pediatrics - Infectious Diseases
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital - Neonatology - Center for Perinatal Research
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital - Pediatrics
state: Rhode Island
city: Houston
country: United States
facility: Texas Medical Center - Texas Children's Hospital
state: Texas
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children - Paediatric Immunology
state: Bristol, City Of
city: London
country: United Kingdom
facility: Saint George's Hospital - Pediatric Infectious Diseases
state: London, City Of
city: London
country: United Kingdom
facility: Great Ormond Street Hospital - Infectious Diseases
state: London, City Of
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Crumpsall
country: United Kingdom
facility: Pennine Acute Hospitals NHS Trust, North Manchester General Hospital - Children's and Adolescent Services
city: Headington, Oxford
country: United Kingdom
facility: John Radcliffe Hospital - Children's Hospital - Paediatric Infectious Disease and Immunology
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Great North Children's Hospital - Paediatric Immunology
city: Sheffield
country: United Kingdom
facility: Sheffield Children's Hospital - Immunology
city: Southampton, Hampshire
country: United Kingdom
facility: Southampton Children's Hospital - Allergy, Immunology and Infection
Study officials:
References: