A Multi-Center, Phase 2, Open Label, Ascending Dose Study to Evaluate the Safety and Efficacy of RVP-001 and to Identify an Appropriate Dose to Detect CNS Lesions in Adult Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 5
- 主要终点
- Adverse Events
研究概览
简要总结
This Phase 2 clinical trial will study RVP-001, a new manganese-based MRI contrast agent, in people who are known to have gadolinium-enhancing central nervous system (CNS) lesions, for example brain tumors or multiple sclerosis.
The goal of this study is to assess safety, efficacy, and pharmacokinetics of RVP-001 at three dose levels. The study will also compare RVP-001 imaging to gadolinium-based contrast agent (GBCA) imaging. A single dose of RVP-001 will be administered to each subject. Subjects will have known gadolinium-enhancing CNS lesions and will have a gadolinium-based contrast agent-enhanced MRI of the brain 2-14 days before receiving RVP-001 with imaging.
The ultimate goal of this research program is development of a gadolinium-free alternative to current general purpose MRI contrast agents.
详细描述
Subjects may include individuals who have a stable primary brain tumor, metastatic brain tumors, multiple sclerosis, or other gadolinium-enhancing CNS lesions. Following the screening GBCA-enhanced MRI scan to confirm presence of target lesion(s), a baseline unenhanced MRI scan will be performed prior to RVP-001 injection. Dynamic imaging will be performed in conjunction with RVP-001 injection. Steady state imaging will follow at multiple time points during the first hour following dose administration to characterize the pharmacodynamics of RVP-001 and to assess its ability to enhance visualization of areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system.
Three dose cohorts are planned.
An unenhanced MRI scan follow-up study will be performed between one week and six weeks following the administration of RVP-001.
Safety will be evaluated throughout the study by assessing the following parameters: adverse events (AEs), physical examinations, injection site monitoring, electrocardiograms (ECGs), vital signs, clinical laboratory evaluations, medical history, and prior and concomitant medications.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults of all sexes, aged 18-75 years
- •Patients with known enhancing CNS lesions, including but not limited to gliomas, meningiomas, glioblastomas, schwannomas, brain metastases, multiple sclerosis lesions, that are on an ongoing follow-up MRI schedule
- •Patients who have had a GBCA-enhanced MRI within the past 14 days which demonstrated focal areas of disrupted Blood Brain Barrier (BBB) (e.g., primary and secondary tumors, focal inflammatory disorders) including at least one enhancing lesion of minimum 5 mm (long axis)
- •Acceptable renal function
排除标准
- •Serious non-malignant disease that could compromise protocol objectives in the opinion of the investigator and/or the Sponsor
- •Body mass index (BMI) greater than 35
- •Patients with clinically significant cardiac disease
- •MRI incompatibility
研究组 & 干预措施
2 mg/Mn/kg
6 subjects each will receive RVP-001 at a dose of 2 mg Mn/kg
干预措施: RVP-001 (Drug)
7 mg/Mn/kg
6 subjects each will receive RVP-001 at a dose of 7 mg Mn/kg
干预措施: RVP-001 (Drug)
12 mg/Mn/kg
6 subjects each will receive RVP-001 at a dose of 12 mg Mn/kg
干预措施: RVP-001 (Drug)
结局指标
主要结局
Adverse Events
时间窗: From time of dosing to 7 days post dose
Treatment-emergent adverse events for each dose level will be summarized.
Lesion visualization criteria for RVP-001 enhanced MRI compared to unenhanced MRI
时间窗: 1 day
The lesion visualization criteria is based on 3 criteria: border delineation, lesion contrast, and internal morphology. These criteria will be assessed by independent readers for representative lesions using the images acquired during the MRI performed with RVP-001.
Lesion visualization criteria for RVP-001 compared to gadolinium-based contrast agent (GBCA)
时间窗: 1 day
The lesion visualization criteria is based on 3 criteria: border delineation, lesion contrast, and internal morphology. These criteria will be assessed by independent readers for representative lesions using the images acquired with RVP-001 and those acquired with the GBCA. For each reader, only matching lesion-pairs present in both MRI image sets (using GBCA and RVP-001) will be considered.
次要结局
未报告次要终点