Asymptomatic Congenital CMV Treatment

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03301415
• Collaborator: (none)
• Enrollment: 229
• Locations: 9
• Arm: 1
• Anticipated Duration (Months): 68
• Patients Per Site: 25.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

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 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. 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.

Study Design

• Study Type: Interventional
• Anticipated 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: Apr 2, 2019
• Anticipated Primary Completion Date: Jul 1, 2024
• Anticipated Study Completion Date: Dec 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. The number of subjects developing sensorineural hearing loss in at least one ear [Between baseline and study month 6]

Secondary Outcome Measures

1. Cumulative incidence of absolute neutrophil counts below 500/mm^3 [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 [Study month 4]

3. Cumulative incidence of grade 3 or higher safety laboratory adverse events [From day 1 through study month 6]

4. Cumulative incidence of grade 3 or higher serious adverse events [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 [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 [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 [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 [Study Months 4, 6, 12, and 18]

9. Cumulative incidence of sensorineural hearing loss in at least one ear [Between baseline and study month 12]

10. Cumulative incidence of sensorineural hearing loss in at least one ear [Between baseline and study month 18]

11. Cumulative incidence of sensorineural hearing loss in at least one ear [Between baseline and study month 4]

12. Cumulative incidence of severe worsened hearing, represented by the ear that has the larger degree of worsening [Study Months 4, 6, 12, and 18]

13. Cumulative incidence of transaminase elevation during treatment > / = 2 times the baseline value [Study month 5]

14. Proportion of ears of mild worsened hearing [Study Months 4, 6, 12, and 18]

15. Proportion of ears of moderate worsened hearing [Study Months 4, 6, 12, and 18]

16. Proportion of ears of profound worsened hearing [Study Months 4, 6, 12, and 18]

17. Proportion of ears of severe worsened hearing [Study Months 4, 6, 12, and 18]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Day to 30 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama - Children's of Alabama - Clinical Virology	Birmingham	Alabama	United States	35233-1711
2	Arkansas Children's Hospital - Infectious Diseases	Little Rock	Arkansas	United States	72202
3	University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases	Louisville	Kentucky	United States	40202
4	University of Mississippi - Children's Infectious Diseases	Jackson	Mississippi	United States	39216-4505
5	Washington University School of Medicine in St. Louis - Center for Clinical Studies	Saint Louis	Missouri	United States	63110-1010
6	Carolinas Medical Center - Pediatrics - Infectious Diseases	Charlotte	North Carolina	United States	28203-5812
7	Nationwide Children's Hospital - Neonatology - Center for Perinatal Research	Columbus	Ohio	United States	43205-2664
8	Children's Hospital of Pittsburgh of UPMC - Pediatric Infectious Diseases	Pittsburgh	Pennsylvania	United States	15224-1529
9	Texas Medical Center - Texas Children's Hospital	Houston	Texas	United States	77030-2303

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03301415
• Other Study ID Numbers: 16-0095
• First Posted: Oct 4, 2017
• Last Update Posted: Aug 22, 2022
• Last Verified: Apr 1, 2022

• 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: Infections; Cytomegalovirus Infections; Valganciclovir

Study Results

No Results Posted as of Aug 22, 2022