Safety and Tolerability of Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of treatment-related adverse events (AEs) of Grade 3 severity or higher as determined by Common Terminology Criteria for Adverse Events (CTCAE)
研究概览
简要总结
Background:
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal brain infection caused by the JC virus. The JC virus is common. More than half of adults have been exposed to it. Most people do not get sick from the JC virus, but in people with weakened immune systems, it can cause PML. Brincidofovir (BCV) is an antiviral drug approved to treat smallpox. Researchers want to know if it can help people with PML.
Objective:
To test BCV in people with PML.
Eligibility:
People aged 18 years or older with PML.
Design:
Participants will be screened. They will have a physical exam with blood tests. They will have an imaging scan of the brain with contrast dye. They will have a lumbar puncture (spinal tap): A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord.
BCV will be given through a tube attached to a needle inserted into a vein. Participants will receive the drug 2 times a week for 4 weeks (this is 1 cycle). If the drug is helping them, they may have up to 3 drug cycles (12 weeks).
Imaging scans, spinal taps, and other tests will be repeated after every 4 weeks of treatment. Participants will have 6 follow-up visits in 1 year after treatment ends. The imaging scan, spinal tap, and other tests will be repeated at each visit.
详细描述
Study Description:
This pilot study will test safety and tolerability of IV BCV as an antiviral treatment strategy for participants with PML, and will collect preliminary data on biological and clinical impact on PML disease course. Eighteen adults with PML from all causes will complete this study.
Following a standardized baseline evaluation and confirmation of PML diagnosis with positive JCPyV DNA detection in CSF, participants will receive IV BCV 20mg (or 0.4mg/kg if participant weighs<50kg) twice weekly in 4-week Infusion Cycles for up to 12 weeks total (3 Infusion Cycles).
At completion of each Infusion Cycle, participants will be evaluated monthly for 3 months to determine if they meet criteria for 1) redosing with additional 4-weeks of IV BCV, 2) initiation/continuation of Clinical Monitoring or 3) definition of Treatment Failure (leading to optional withdrawal from study and pursuit of rescue treatments). As long as less than 12 weeks of cumulative dosing have been pursued, redosing may be offered.
Upon completion of treatment, participants will be monitored for up to 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •Able to provide informed consent or have a designated legally authorized representative (LAR) to provide consent
- •Stated willingness to comply with study procedures and to participate for the duration of the study including follow-up
- •Actively progressing, clinically definite or probable PML (2013 AAN Consensus Diagnostic Criteria)
- •Positive PCR for JCPyV in CSF
- •Age 18 or older
- •Medically stable and able to tolerate travel to NIH
- •Participants of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
排除标准
- •ALT or AST > 5 x the ULN, total bilirubin > 3 mg/dL (SI: >51 micromol/L), or spontaneous prothrombin time-international normalized ratio (PT-INR) > 2 x ULN within 7 days prior to Day 1
- •An estimated glomerular filtration rate of < 30 mL/min within 7 days prior to Day 1
- •Hypersensitivity to CDV or to BCV or its formulation excipients, or prior intolerance to these agents that, in the opinion of the investigator, would pose an unacceptable safety risk.
- •Active CNS disease other than PML that, in the opinion of the investigator, would confound study assessments or pose an unacceptable safety risk.
- •Contraindication to MRI (including cardiac pacemakers and some infusion pumps, other metallic implants, metallic foreign objects)
- •Medical contraindication to LP
- •Positive pregnancy test or nursing
研究组 & 干预措施
Brincidofovir treatment arm
experimental treatment arm
干预措施: Brincidofovir (Drug)
结局指标
主要结局
Incidence of treatment-related adverse events (AEs) of Grade 3 severity or higher as determined by Common Terminology Criteria for Adverse Events (CTCAE)
时间窗: Over duration of trial participation
次要结局
- Proportion of patients with 0.25log decline or greater in JCPyV load in CSF upon completion of each Treatment Block(at end of each treatment block)
- Time to increase in JCPyV load in CSF during monitoring phase upon treatment completion(over duration of trial participation)
- Number of Treatment Blocks and duration of treatment phase(dependent on duration of participation: 1 month - 3 months)
- Number of patients meeting Treatment Failure Criteria(At end of each treatment block)
- Change from baseline in performance and standardized disability rating scales at 6, 9 and 12 months(6, 9 and 12 months)
- Change from baseline in PML lesion burden by brain MRI at 3, 6 9 and 12 months(3, 6, 9 and 12 months)
- Survival at 3, 6, 9 and 12 months(3, 6, 9 and 12 months)
- Incidence of treatment-related AEs, regardless of severity(over duration of trial)
- Change from baseline in JCPyV load in CSF upon completion of each Treatment Block(at end of each treatment block)