Asymptomatic Congenital CMV Treatment

NCT03301415 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 16-0095
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 9

Brief Summary

This is a phase II, open-label trial to evaluate valganciclovir as a treatment to prevent development of sensorineural hearing loss (SNHL) in infants with asymptomatic congenital cytomegalovirus (CMV) infection. The trial will be conducted in two phases - screening of newborns to identify eligible subjects, and treatment of those newborns who have confirmed CMV infection at birth but without outward manifestations of congenital CMV infection. 229 newborns with confirmed CMV infection but without baseline SNHL and who meet all inclusion/exclusion criteria will be enrolled into the treatment phase. Study duration is 5 years. Primary objective of this study is to estimate the proportion of subjects with asymptomatic congenital CMV infection who, following treatment with 4 months of oral valganciclovir, develop SNHL by 6 months of life.

Conditions

Congenital Cytomegalovirus Infection

Keywords

Asymptomatic; Congenital CMV Infection; Valganciclovir Therapy

Outcome Measures

Primary Outcomes (1)

• The Number of Participants Developing Sensorineural Hearing Loss (SNHL) in at Least One Ear Between Baseline and Study Month 6

  Audiologic assessments were made during the Screening Period and Study Months 4 (end of treatment), 6, 12, and 18. A single, independent study audiologist assessed the audiology test battery for each subject and assigned each ear the classifications of normal hearing, mild hearing loss, moderate hearing loss, severe hearing loss, or profound hearing loss based upon their hearing thresholds (in decibels). SNHL between baseline and Study Month 6 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 6 month follow-up.

  Between baseline and study month 6

Secondary Outcomes (17)

• Number of Participants With Absolute Neutrophil Counts Below 500/mm^3

  Day 1 through Study month 5

• Number of Participants With Adverse Events Leading to Permanent Discontinuation of Valganciclovir Therapy, or Any Adverse Event That is Not Recovered / Not Resolved

  Day 1 through Study month 6

• Number of Participants With Grade 3 or Higher Safety Laboratory Adverse Events

  From day 1 through study month 6

• Number of Participants With Serious Adverse Events

  From day 1 through study month 6

• Number of Participants With Grade 3 or Higher Unsolicited Adverse Events Assessed by Adapted From DAIDS Toxicity Tables

  From day 1 through study month 6

Study Arms (1)

Confirmed congenital CMV without baseline SNHL

EXPERIMENTAL

Valganciclovir 16 mg/kg/dose orally twice daily for four months, n=229

Drug: Valganciclovir

Interventions

Valganciclovir DRUG

Valganciclovir, 16 mg/kg/dose given orally twice daily for four months

Confirmed congenital CMV without baseline SNHL

Eligibility Criteria

• Age: 1 Day - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Parent(s)/legal guardian(s) have signed informed consent documents\*
• Confirmation of cytomegalovirus (CMV) by urine polymerase chain reaction (PCR) testing
• Infant \</= 30 days of age at initiation of study drug
• Weight at study enrollment \>/= 1775 grams
• Gestational age \>/= 32 weeks at birth
• There is a screening informed consent for screening phase of study participation, and a treatment informed consent for treatment phase of study participation.

You may not qualify if:

• Symptomatic congenital cytomegalovirus (CMV) disease\*
• Sensorineural hearing deficits as detected by formal brainstem evoked response (not a screening auditory brainstem response (abr)) of known etiology other than CMV
• Prior or current receipt of ganciclovir, valganciclovir, foscarnet, cidofovir, brincidofovir, maribavir, or letermovir
• Maternal receipt of CMV hyperimmune globulin during pregnancy
• Breastfeeding from mother who is receiving ganciclovir, valganciclovir, foscarnet, cidofovir, brincidofovir, maribavir, or letermovir
• Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis)
• Infants known to be born to women who are HIV positive (HIV testing is not required for study entry)
• Current receipt of other investigational drugs
• Symptomatic disease is defined as one or more of the following: 1) thrombocytopenia, if known; 2) petechiae; 3) hepatomegaly; 4) splenomegaly; 5) intrauterine growth restriction; 6) hepatitis (elevated transaminases and/or direct bilirubin), if known; 7) central nervous system involvement of the CMV disease (such as microcephaly; radiographic abnormalities indicative of CMV CNS disease, if known; abnormal CSF indices for age, if known; chorioretinitis, if known; and/or positive CMV PCR from CSF, if known).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (9)

University of Alabama - Children's of Alabama - Clinical Virology

Birmingham, Alabama, 35233-1711, United States

Location

Arkansas Children's Hospital - Infectious Diseases

Little Rock, Arkansas, 72202, United States

Location

University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases

Louisville, Kentucky, 40202, United States

Location

University of Mississippi - Children's Infectious Diseases

Jackson, Mississippi, 39216-4505, United States

Location

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

St Louis, Missouri, 63110-1010, United States

Location

Carolinas Medical Center - Pediatrics - Infectious Diseases

Charlotte, North Carolina, 28203-5812, United States

Location

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

Columbus, Ohio, 43205-2664, United States

Location

Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases

Pittsburgh, Pennsylvania, 15224-1529, United States

Location

Texas Medical Center - Texas Children's Hospital

Houston, Texas, 77030-2303, United States

Location

MeSH Terms

Conditions

Cytomegalovirus Infections

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

The trial was stopped early due to low accrual with only 7 participants enrolled.

Results Point of Contact

• Title: David W. Kimberlin, MD
• Organization: The University of Alabama at Birmingham

dkimberlin@peds.uab.edu

205-934-5316

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: October 4, 2017
• Study Start: August 21, 2019
• Primary Completion: November 5, 2020
• Study Completion: November 5, 2020
• Last Updated: January 26, 2023
• Results First Posted: January 26, 2023

Record last verified: 2018-10

Locations

US (9)