A Clinical Study Evaluating a Recombinant Adeno-Associated Virus Serotype 9 (rAAV9) Capsid Containing the Human Lysosome-Associated Membrane Protein 2 Isoform B (LAMP2B) Transgene (RP-A501; AAV9.LAMP2B) in Male Patients With DD
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 7
- 试验地点
- 6
- 主要终点
- Evaluation of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy
研究概览
简要总结
This is a non-randomized open-label Phase 1 study to evaluate the safety and toxicity of gene therapy using a recombinant adeno-associated virus serotype 9 (AAV9) containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon Disease (DD).
详细描述
The study is a non-randomized open-label Phase I clinical trial to characterize the safety and toxicity associated with infusion of a recombinant adeno-associated serotype 9 (rAAV9) capsid containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon Disease (DD).
During the course of the study, approximately 7-10 male subjects age 8 and over will receive a single intravenous (IV) infusion of the IP. Prior to infusion of IP, rituximab and sirolimus will be administered prophylactically.
All patients are planned to be followed for 36 months after investigational product administration. After the end of the follow-up period, patients will enter a Long-Term Follow-Up (LTFU) study enabling follow-up for an additional 2 to 5 years post-IP administration.
The study will also enable an initial evaluation of whether or not the IP results in cardiomyocyte and skeletal muscle transduction and gene expression and preliminary assessment of the extent of cardiomyocyte and histologic correction. Additionally, a preliminary evaluation of clinical stabilization following infusion will also be made.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Evaluation of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy
时间窗: 3 years
Assessment of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy
Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE)
时间窗: 3 years
Evaluation of safety associated with RP-A501
Number of participants within each dose level cohort with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE)
时间窗: 3 years
Assessment of safety at both doses (single IV administration)
Preliminary evaluation of clinical stabilization of cardiomyopathy following administration of RP-A501 via cardiopulmonary testing
时间窗: 3 years
Assessment of clinical stabilization of cardiomyopathy following infusion of RP-A501 via cardiopulmonary testing
次要结局
- Determination of the percentage of patients in whom RP-A501 resulted in a sustained improvement or stabilization in cardiovascular pathophysiology(3 years)
- Determination of the percentage of patients in whom cardiomyocytes corrected LAMP2B gene and/or protein(3 years)
- Evaluation of overall survival(3 years)
- Determination and characterization of immunologic response to RP-A501(3 years)
- Determination of the percentage of patients who require and/or receive treatment for heart failure following RP-A501(3 years)