Congenital Cytomegalovirus Infection
Conditions
Keywords
Asymptomatic, Congenital CMV Infection, Valganciclovir Therapy
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.
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.
Interventions
DRUGValganciclovir
Valganciclovir, 16 mg/kg/dose given orally twice daily for four months
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 30 Days
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Developing Sensorineural Hearing Loss (SNHL) in at Least One Ear Between Baseline and Study Month 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | A count of participants discontinued from valganciclovir therapy due to adverse events were reported during the therapy period, and the count of participants with adverse events not recovered/not resolved were reported throughout the adverse event period. |
| Number of Participants With Grade 3 or Higher Safety Laboratory Adverse Events | From day 1 through study month 6 | At each study visit from the receipt of first dose of study drug and continuing through four weeks following the final dose of study drug, the participants were assessed for any adverse events. Lab parameters included ALT, creatinine, direct bilirubin, white blood cell count with differential, hemoglobin, platelets count. Abnormal laboratory values were reported as an AE if they worsened in severity from baseline, per the grading definitions provided in the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. |
| Number of Participants With Serious Adverse Events | From day 1 through study month 6 | Serious adverse events were those defined as: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or were important medical events that may not result in death, be life-threatening, or require hospitalizations may be considered serious when, based upon appropriate medical judgment they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. |
| 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 | At each study visit from the receipt of first dose of study drug and continuing through four weeks following the final dose of study drug, the participants were assessed for any adverse events. Lab parameters included ALT, creatinine, direct bilirubin, white blood cell count with differential, hemoglobin, platelets count. Abnormal laboratory values were reported as an AE if they worsened in severity from baseline, per the grading definitions provided in the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. |
| Number of Participants With Mild Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Screening and Study Months 4, 6, 8 and 12 | 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 participant 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up. |
| Number of Participants With Moderate Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Screening and Study Months 4, 6, 8 and 12 | 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up. |
| Number of Participants With Profound Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Study Months 4, 6, 8 and 12 | 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 participant 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up. |
| Number of Participants With Severe Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Study Months 4, 6, 8 and 12 | 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 participant 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up. |
| Number of Participants With Absolute Neutrophil Counts Below 500/mm^3 | Day 1 through Study month 5 | Blood was collected for assessments of hematology and absolute neutrophil count was assessed at each study visit through Month 5 |
| Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 12 | Between screening and study month 12 | 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 participant 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 12 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 12 month follow-up. |
| Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 18 | Between screening and study month 18 | 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 participant 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up. |
| Number of Participants With Transaminase Elevation During Treatment > / = 2 Times the Baseline Value | Baseline, weeks 2, 4, 6, 8, 10, 12, months 4, 5 and 6. | Blood was collected for assessments of clinical chemistry and alanine aminotransferase (ALT) was assessed at screening, week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Month 4, Month 5, and Month 6 |
| Number of Ears of Mild Worsened Hearing | Screening and Study Months 4, 6, 12, and 18 | 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 participant 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). |
| Number of Ears of Moderate Worsened Hearing | Screening and Study Months 4, 6, 12, and 18 | 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 participant 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). |
| Number of Ears of Profound Worsened Hearing | Screening and Study Months 4, 6, 12, and 18 | 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 participant 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). |
| Number of Ears of Severe Worsened Hearing | Screening and Study Months 4, 6, 12, and 18 | 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 participant 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). |
| Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 4 | Between screening and study month 4 | 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 participant 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 4 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 4 month follow-up. |
Countries
United States
Participant flow
Recruitment details
Male and female infants with asymptomatic congenital CMV infection were recruited at participating sites between 20Aug2019 and 09SEP2020.
Participants by arm
| Arm | Count |
|---|---|
| Confirmed Congenital CMV Without Baseline SNHL Valganciclovir, 16 mg/kg/dose given orally twice daily for four months | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Unable to comply with visit schedule | 2 |
Baseline characteristics
| Characteristic | Confirmed Congenital CMV Without Baseline SNHL |
|---|---|
| Age, Categorical <=18 years | 7 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 25.7 days STANDARD_DEVIATION 3.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
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.
Time frame: Between baseline and study month 6
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study month 6 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | The Number of Participants Developing Sensorineural Hearing Loss (SNHL) in at Least One Ear Between Baseline and Study Month 6 | 0 Participants |
Secondary
Number of Ears of Mild Worsened Hearing
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 participant 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).
Time frame: Screening and Study Months 4, 6, 12, and 18
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study months 4, 6, 12, 18.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Mild Worsened Hearing | Month 4 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Mild Worsened Hearing | Month 6 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Mild Worsened Hearing | Month 12 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Mild Worsened Hearing | Month 18 | 0 Ears |
Secondary
Number of Ears of Moderate Worsened Hearing
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 participant 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).
Time frame: Screening and Study Months 4, 6, 12, and 18
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study months 4, 6, 12, 18.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Moderate Worsened Hearing | Month 4 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Moderate Worsened Hearing | Month 6 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Moderate Worsened Hearing | Month 12 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Moderate Worsened Hearing | Month 18 | 0 Ears |
Secondary
Number of Ears of Profound Worsened Hearing
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 participant 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).
Time frame: Screening and Study Months 4, 6, 12, and 18
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study months 4, 6, 12, 18.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Profound Worsened Hearing | Month 18 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Profound Worsened Hearing | Month 4 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Profound Worsened Hearing | Month 6 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Profound Worsened Hearing | Month 12 | 0 Ears |
Secondary
Number of Ears of Severe Worsened Hearing
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 participant 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).
Time frame: Screening and Study Months 4, 6, 12, and 18
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study months 4, 6, 12, 18.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Severe Worsened Hearing | Month 4 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Severe Worsened Hearing | Month 6 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Severe Worsened Hearing | Month 12 | 0 Ears |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Ears of Severe Worsened Hearing | Month 18 | 0 Ears |
Secondary
Number of Participants With Absolute Neutrophil Counts Below 500/mm^3
Blood was collected for assessments of hematology and absolute neutrophil count was assessed at each study visit through Month 5
Time frame: Day 1 through Study month 5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Absolute Neutrophil Counts Below 500/mm^3 | 1 Participants |
Secondary
Number of Participants With Adverse Events Leading to Permanent Discontinuation of Valganciclovir Therapy, or Any Adverse Event That is Not Recovered / Not Resolved
A count of participants discontinued from valganciclovir therapy due to adverse events were reported during the therapy period, and the count of participants with adverse events not recovered/not resolved were reported throughout the adverse event period.
Time frame: Day 1 through Study month 6
Population: All participants who have received at least one dose of study product and for whom any data on safety are available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Adverse Events Leading to Permanent Discontinuation of Valganciclovir Therapy, or Any Adverse Event That is Not Recovered / Not Resolved | AEs leading to discontinuation | 1 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Adverse Events Leading to Permanent Discontinuation of Valganciclovir Therapy, or Any Adverse Event That is Not Recovered / Not Resolved | AEs not recovered/resolved | 4 Participants |
Secondary
Number of Participants With Grade 3 or Higher Safety Laboratory Adverse Events
At each study visit from the receipt of first dose of study drug and continuing through four weeks following the final dose of study drug, the participants were assessed for any adverse events. Lab parameters included ALT, creatinine, direct bilirubin, white blood cell count with differential, hemoglobin, platelets count. Abnormal laboratory values were reported as an AE if they worsened in severity from baseline, per the grading definitions provided in the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events.
Time frame: From day 1 through study month 6
Population: All participants who have received at least one dose of study product and for whom any safety data are available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Grade 3 or Higher Safety Laboratory Adverse Events | 4 Participants |
Secondary
Number of Participants With Grade 3 or Higher Unsolicited Adverse Events Assessed by Adapted From DAIDS Toxicity Tables
At each study visit from the receipt of first dose of study drug and continuing through four weeks following the final dose of study drug, the participants were assessed for any adverse events. Lab parameters included ALT, creatinine, direct bilirubin, white blood cell count with differential, hemoglobin, platelets count. Abnormal laboratory values were reported as an AE if they worsened in severity from baseline, per the grading definitions provided in the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events.
Time frame: From day 1 through study month 6
Population: All participants who have received at least one dose of study product and for whom any safety data are available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Grade 3 or Higher Unsolicited Adverse Events Assessed by Adapted From DAIDS Toxicity Tables | 4 Participants |
Secondary
Number of Participants With Mild Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening
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 participant 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up.
Time frame: Screening and Study Months 4, 6, 8 and 12
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study month 12 visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Mild Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 4 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Mild Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Screening | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Mild Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 6 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Mild Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 8 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Mild Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 12 | 0 Participants |
Secondary
Number of Participants With Moderate Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening
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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up.
Time frame: Screening and Study Months 4, 6, 8 and 12
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study month 12 visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Moderate Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Screening | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Moderate Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 4 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Moderate Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 6 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Moderate Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 8 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Moderate Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 12 | 0 Participants |
Secondary
Number of Participants With Profound Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening
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 participant 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up.
Time frame: Study Months 4, 6, 8 and 12
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study month 18 visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Profound Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 6 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Profound Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Screening | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Profound Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 4 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Profound Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 8 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Profound Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 12 | 0 Participants |
Secondary
Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 12
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 participant 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 12 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 12 month follow-up.
Time frame: Between screening and study month 12
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study month 12 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 12 | 0 Participants |
Secondary
Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 18
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 participant 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up.
Time frame: Between screening and study month 18
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study month 18 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 18 | 0 Participants |
Secondary
Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 4
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 participant 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 4 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 4 month follow-up.
Time frame: Between screening and study month 4
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study month 4 visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 4 | 0 Participants |
Secondary
Number of Participants With Serious Adverse Events
Serious adverse events were those defined as: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital anomaly/birth defect, or were important medical events that may not result in death, be life-threatening, or require hospitalizations may be considered serious when, based upon appropriate medical judgment they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Time frame: From day 1 through study month 6
Population: All participants who have received at least one dose of study product and for whom any safety data are available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Serious Adverse Events | 0 Participants |
Secondary
Number of Participants With Severe Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening
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 participant 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 18 is defined as both ears with normal hearing at baseline, then at least one ear with sensorineural hearing loss (SNHL) at the 18 month follow-up.
Time frame: Study Months 4, 6, 8 and 12
Population: All participants who have received at least one dose of study product and with a normal baseline hearing assessment for both ears and with hearing assessment result available at Study month 12 visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Severe Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 4 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Severe Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Screening | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Severe Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 6 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Severe Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 8 | 0 Participants |
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Severe Worsened Hearing, Represented by the Ear That Has the Larger Degree of Worsening | Month 12 | 0 Participants |
Secondary
Number of Participants With Transaminase Elevation During Treatment > / = 2 Times the Baseline Value
Blood was collected for assessments of clinical chemistry and alanine aminotransferase (ALT) was assessed at screening, week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Month 4, Month 5, and Month 6
Time frame: Baseline, weeks 2, 4, 6, 8, 10, 12, months 4, 5 and 6.
Population: All participants who have received at least one dose of study product and for whom with any alanine aminotransferase result available from Day 1 through Month 6.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Confirmed Congenital CMV Without Baseline SNHL | Number of Participants With Transaminase Elevation During Treatment > / = 2 Times the Baseline Value | 0 Participants |