A Phase II, Single Stage, Single-Arm Investigation of Oral Valganciclovir Therapy in Infants With Asymptomatic Congenital Cytomegalovirus Infection
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 9
- 主要终点
- The Number of Participants Developing Sensorineural Hearing Loss (SNHL) in at Least One Ear Between Baseline and Study Month 6
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 30 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
Confirmed congenital CMV without baseline SNHL
Valganciclovir 16 mg/kg/dose orally twice daily for four months, n=229
干预措施: Valganciclovir (Drug)
结局指标
主要结局
The Number of Participants Developing Sensorineural Hearing Loss (SNHL) in at Least One Ear Between Baseline and Study Month 6
时间窗: 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.
次要结局
- 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)
- Number of Participants With Grade 3 or Higher Safety Laboratory Adverse Events(From day 1 through study month 6)
- 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 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)
- Number of Participants With Absolute Neutrophil Counts Below 500/mm^3(Day 1 through Study month 5)
- 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)
- 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)
- Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 12(Between screening and study month 12)
- Number of Ears of Severe Worsened Hearing(Screening and Study Months 4, 6, 12, and 18)
- Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 18(Between screening and study month 18)
- 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)
- Number of Participants With Sensorineural Hearing Loss in at Least One Ear Through Study Month 4(Between screening and study month 4)
- 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.)
- Number of Ears of Mild Worsened Hearing(Screening and Study Months 4, 6, 12, and 18)
- Number of Ears of Moderate Worsened Hearing(Screening and Study Months 4, 6, 12, and 18)
- Number of Ears of Profound Worsened Hearing(Screening and Study Months 4, 6, 12, and 18)