A Phase 1/2, First-in-Human, Open-Label, Multicenter, Single-Dose Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of NVC-001, a Novel Adeno-Associated Virus (Serotype 9) Vector Expressing a Dominant Negative SUN1 Transgene, in Patients With LMNA-Related Dilated Cardiomyopathy (SUNBEAM-LMNA)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 21
- 试验地点
- 8
- 主要终点
- Safety: Frequency, severity, and relatedness of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This study is designed to evaluate the safety and tolerability of NVC-001 in adults with LMNA-related dilated cardiomyopathy (LMNA-DCM). The study will also assess exploratory measures of efficacy.
详细描述
This is a Phase 1/2, open-label study of NVC-001 in adults with LMNA-related dilated cardiomyopathy (LMNA-DCM). The primary objective is to evaluate the safety and tolerability of NVC-001. Secondary and exploratory objectives include characterization of pharmacodynamic effects and assessment of preliminary efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult ≥18 years old, able to provide informed consent
- •Clinical diagnosis of LMNA-related dilated cardiomyopathy (DCM) with LV systolic dysfunction
- •Pathogenic or likely pathogenic LMNA mutation confirmed by a CLIA-certified/CAP-accredited laboratory
- •NYHA Functional Class I, II, or III
- •LVEF >25% and ≤45% by echocardiography
- •Implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator )CRT-D) implanted >3 months prior to consent
排除标准
- •Any chronic medical condition that, in the Investigator's opinion, would compromise participant safety or compliance
- •Hospitalization as an inpatient for the following conditions within 3 months prior to signing the ICF: Heart failure, Persistent/refractory ventricular arrhythmia requiring external defibrillation, or multiple/recurrent cardioversion/defibrillation by ICD Indication for, or history of, LV assist device or cardiac transplantation due to end-stage cardiac dysfunction
- •Current or anticipated need for chronic IV inotropic therapy
研究组 & 干预措施
SAD medium dose
Single Ascending Dose (SAD): participants will receive medium dose of NVC-001
干预措施: NVC-001 - Intermediate Dose (Genetic)
SAD high dose
Single Ascending Dose (SAD): participants will receive high dose of NVC-001
干预措施: NVC-001 - High Dose (Genetic)
SAD low dose
Single Ascending Dose (SAD): participants will receive low dose of NVC-001
干预措施: NVC-001 - Low Dose (Genetic)
结局指标
主要结局
Safety: Frequency, severity, and relatedness of treatment-emergent adverse events (TEAEs)
时间窗: At week 26
次要结局
- Change in exercise capacity(Up to 104 weeks)
- Change in echocardiographic parameters(Up to 104 weeks)
- Change from baseline in arrhythmias(Up to 104 weeks)
- Change from baseline in quality of life (QoL)(Up to 104 weeks)
- Incidence of clinical events(Up to week 104)