A Safety and Dose-Determining Study of CMX001 In Infants With Neonatal Herpes Simplex Virus (HSV) Infection Involving the Central Nervous System (CNS Disease)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 18
- 主要终点
- Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
研究概览
简要总结
This study is to identify if a Novel Antiviral Drug could be used to treat babies with Herpes Simplex Virus (HSV) with central nervous system (CNS) disease. In this study the investigators will identify the best dose for young children as well as identify additional safety information about the Novel Antiviral Drug.
详细描述
In this study, the pharmacokinetics and safety of a Novel Antiviral Drug will be determined in babies with neonatal HSV CNS disease. The study will be conducted at 18 academic medical centers throughout the United States. Young infants presenting with virologic confirmation of neonatal HSV infection and evidence of CNS involvement will be eligible for study enrollment. Study Day 1 is defined as the day when dose 1 of the Novel Antiviral Drug study medication is administered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 1 Day 至 98 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent by parent or legal guardian of study subject
- •Virologically confirmed HSV infection [e.g., positive culture, DNA detection by polymerase chain reaction (PCR), or direct fluorescent antibody stain from any body site or compartment]
- •Evidence of CNS involvement of HSV disease [e.g., CSF pleocytosis, positive CSF PCR testing, clinical or electroencephalogram (EEG) seizure activity, neuroimaging abnormality)
- •Starting parenteral acyclovir therapy at time of initiation of CMX001 study drug or receiving parenteral acyclovir therapy for ≤ 72 hours before start CMX001 study drug
- •≤ 6 weeks (42 days) of age at time of initial onset of disease symptoms or signs
- •Weight at study enrollment ≥ 2,630 grams
- •Gestational age ≥ 36 weeks at delivery
- •Mother tested negative for HIV during or following pregnancy
排除标准
- •Imminent demise
- •Disseminated or skin/eye/mouth (SEM) neonatal HSV disease classifications
- •Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., history of necrotizing enterocolitis, gastroschisis, malrotation, etc.)
- •Birth weight < 2,500 grams
- •Birth weight > 4,500 grams
- •Grade 3 or 4 vomiting, utilizing the DAIDS Toxicity Tables (Appendix B)
- •Grade 3 or 4 diarrhea, utilizing the DAIDS Toxicity Tables (Appendix B)
- •Creatinine clearance < 15 mL/min/1.73m2
- •Serum albumin < 2.0 g/dL
- •Alanine aminotransferase (ALT) ≥ 2.6-times upper limit normal (ULN)
- •Aspartate aminotransferase (AST) ≥ 2.6-times upper limit normal (ULN)
- •Direct bilirubin > 2 mg/dL
- •Known immunodeficiency
- •Known congenital infection (e.g., symptomatic congenital cytomegalovirus infection; syphilis; congenital toxoplasmosis)
- •Congenital heart disease (e.g., patent ductus arteriosus, Tetralogy of Fallot, hypoplastic left heart syndrome, AV canal, VSD, ASD, transposition of the great arteries, hypoplastic right ventricle, truncus arteriosus, pulmonic stenosis, Ebstein anomaly, coarctation of the aorta, interrupted aortic arch, double outlet right ventricle, dilated cardiomyopathy)
- •Infants currently receiving or anticipated to need treatment with digoxin that cannot be withheld for the duration of CMX001 therapy
- •Infants currently receiving or anticipated to need treatment with ketaconazole that cannot be withheld for the duration of CMX001 therapy
- •Receipt of investigation drugs within 30 days prior to enrollment
- •Concurrent enrollment or participation in any other interventional research study
研究组 & 干预措施
Novel Antiviral Drug
Subjects will be randomized to receive one of 3 oral doses of a Novel Antiviral Drug: 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered
干预措施: Novel Antiviral Drug (Drug)
Placebo
Subjects will be randomized to receive one of 3 oral doses of placebo matched in volume to active drug: 0.50 mg/kg/dose, 1.0 mg/kg/dose or 2.0 mg/kg/dose twice a week for up to 3 weeks during the time in which the 21 day administration of parenteral acyclovir is being administered
干预措施: Placebo (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
时间窗: Baseline through day 21
Determine the plasma pharmacokinetics of the CMX001 and cidofovir following administration of CMX001 oral suspension in infants being treated for neonatal HSV CNS disease.
时间窗: Baseline through day 21
次要结局
- Explore a plasma drug concentration-response relationship between cidofovir exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy(Baseline through day 56 (end of study))
- Explore a plasma drug concentration-response relationship between CMX001 exposure and quantity of HSV DNA in cerebrospinal fluid (CSF) at Day 4 of antiviral therapy(Baseline through day 21)
研究者
David Kimberlin, MD
Principal Investigator
University of Alabama at Birmingham