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Asymptomatic Congenital CMV Treatment

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ClinicalTrials.gov Identifier: NCT03301415
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a phase II, open-label trial to evaluate valganciclovir as a treatment to prevent development of SNHL in infants with asymptomatic congenital 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 sensorineural hearing loss (SNHL) by 6 months of life.

Condition or disease Intervention/treatment Phase
Congenital Cytomegalovirus Infection Drug: Valganciclovir Phase 2

Detailed Description:

This is a phase II, open-label trial to evaluate valganciclovir as a treatment to prevent development of SNHL in infants with asymptomatic congenital 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. Approximately 48,250 newborn infants with no outward manifestations of congenital CMV infection will be screened to detect approximately 241 neonates with asymptomatic congenital CMV infection; these 241 newborns then will have audiology examinations to determine baseline hearing, with approximately 229 having normal hearing in both ears. Those 229 newborns with confirmed CMV infection but without baseline SNHL and who meet all inclusion/exclusion criteria will be enrolled into the treatment phase. Enrolled subjects will be treated for four months with oral valganciclovir (16 mg/kg/dose, administered two times per day). Audiologic assessments will be made during the Screening Period and Study Months 4 (end of treatment), 6, 12, and 18. Treated infants will be followed for safety throughout the first 6 months of the study (including for 2 months post-treatment). 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 sensorineural hearing loss (SNHL) by 6 months of life. Secondary objectives are to: 1) define the safety and tolerability of valganciclovir in enrolled subjects, 2) estimate the proportion of subjects with asymptomatic congenital CMV infection who, following treatment with 4 months of oral valganciclovir, develop SNHL over the first 18 months of life.

Substudy:

Through the screening process, approximately 12 neonates congenitally infected with CMV who have SNHL at birth also will be identified. Newborn patients with SNHL and who are being treated clinically with valganciclovir will be offered enrollment into an observational substudy.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 229 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Single Stage, Single-Arm Investigation of Oral Valganciclovir Therapy in Infants With Asymptomatic Congenital Cytomegalovirus Infection
Actual Study Start Date : March 20, 2019
Estimated Primary Completion Date : July 1, 2024
Estimated Study Completion Date : December 1, 2024


Arm Intervention/treatment
Experimental: Confirmed congenital CMV without baseline SNHL
Valganciclovir 16 mg/kg/dose orally twice daily for four months, n=229
Drug: Valganciclovir
Valganciclovir, 16 mg/kg/dose given orally twice daily for four months




Primary Outcome Measures :
  1. The number of subjects developing sensorineural hearing loss in at least one ear [ Time Frame: Between baseline and study month 6 ]

Secondary Outcome Measures :
  1. Cumulative incidence of absolute neutrophil counts below 500/mm^3 [ Time Frame: Study month 5 ]
  2. Cumulative incidence of adverse events leading to permanent discontinuation of valganciclovir therapy, or any adverse event that is not recovered / not resolved [ Time Frame: Study month 4 ]
  3. Cumulative incidence of grade 3 or higher safety laboratory adverse events [ Time Frame: From day 1 through study month 6 ]
  4. Cumulative incidence of grade 3 or higher serious adverse events [ Time Frame: From day 1 through study month 5 ]
  5. Cumulative incidence of grade 3 or higher unsolicited adverse events assessed by adapted from DAIDS toxicity tables [ Time Frame: From day 1 through study month 5 ]
  6. Cumulative incidence of mild worsened hearing, represented by the ear that has the larger degree of worsening [ Time Frame: Study Months 4, 6, 12, and 18 ]
  7. Cumulative incidence of moderate worsened hearing, represented by the ear that has the larger degree of worsening [ Time Frame: Study Months 4, 6, 12, and 18 ]
  8. Cumulative incidence of profound worsened hearing, represented by the ear that has the larger degree of worsening [ Time Frame: Study Months 4, 6, 12, and 18 ]
  9. Cumulative incidence of sensorineural hearing loss in at least one ear [ Time Frame: Between baseline and study month 12 ]
  10. Cumulative incidence of sensorineural hearing loss in at least one ear [ Time Frame: Between baseline and study month 18 ]
  11. Cumulative incidence of sensorineural hearing loss in at least one ear [ Time Frame: Between baseline and study month 4 ]
  12. Cumulative incidence of severe worsened hearing, represented by the ear that has the larger degree of worsening [ Time Frame: Study Months 4, 6, 12, and 18 ]
  13. Cumulative incidence of transaminase elevation during treatment > / = 2 times the baseline value [ Time Frame: Study month 5 ]
  14. Proportion of ears of mild worsened hearing [ Time Frame: Study Months 4, 6, 12, and 18 ]
  15. Proportion of ears of moderate worsened hearing [ Time Frame: Study Months 4, 6, 12, and 18 ]
  16. Proportion of ears of profound worsened hearing [ Time Frame: Study Months 4, 6, 12, and 18 ]
  17. Proportion of ears of severe worsened hearing [ Time Frame: Study Months 4, 6, 12, and 18 ]


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Ages Eligible for Study:   up to 30 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Parent(s)/legal guardian(s) have signed informed consent documents*
  • Confirmation of CMV by urine 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.

Exclusion Criteria:

  • Symptomatic congenital CMV disease*
  • Sensorineural hearing deficits as detected by formal brainstem evoked response (not a screening 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03301415


Contacts
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Contact: David W Kimberlin 12059345316 dkimberlin@peds.uab.edu

Locations
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United States, Alabama
University of Alabama - Children's of Alabama - Clinical Virology Recruiting
Birmingham, Alabama, United States, 35233-1711
United States, Arkansas
Arkansas Children's Hospital - Infectious Diseases Recruiting
Little Rock, Arkansas, United States, 72202
United States, Kentucky
University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases Recruiting
Louisville, Kentucky, United States, 40202
United States, Mississippi
University of Mississippi - Children's Infectious Diseases Recruiting
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Washington University School of Medicine in St. Louis - Center for Clinical Studies Recruiting
Saint Louis, Missouri, United States, 63110-1010
United States, North Carolina
Carolinas Medical Center - Pediatrics - Infectious Diseases Recruiting
Charlotte, North Carolina, United States, 28203-5812
United States, Ohio
Nationwide Children's Hospital - Neonatology - Center for Perinatal Research Recruiting
Columbus, Ohio, United States, 43205-2664
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases Recruiting
Pittsburgh, Pennsylvania, United States, 15224-1529
United States, Texas
Texas Medical Center - Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030-2303
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03301415     History of Changes
Other Study ID Numbers: 16-0095
HHSN272201600017C
First Posted: October 4, 2017    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: October 25, 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Asymptomatic
Congenital CMV Infection
Valganciclovir Therapy

Additional relevant MeSH terms:
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Infection
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Valganciclovir
Antiviral Agents
Anti-Infective Agents