NCT06228924招募中1 期
First-in-Human, Open-Label, Safety, Tolerability, Dose-Finding, Pharmacodynamic and Cardiac Transgene Expression Study of TN-401, a Recombinant Adeno-associated Virus Serotype 9 (AAV9) Containing Plakophilin-2 (PKP2) Transgene, in Adults with PKP2 Mutation-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
适应症
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 14
- 主要终点
- Number and severity of Adverse Events over the course of the study.
研究概览
简要总结
This first-in-human study is designed to evaluate the safety, and preliminary efficacy (PD) of TN-401 gene therapy in adult patients with symptomatic PKP2 mutation-associated ARVC.
详细描述
The RIDGE-1™ open-label Safety, Tolerability, Dose-finding, PD and Cardiac Transgene Expression Study will enroll up to 15 patients in two planned dose cohorts. Patients in each cohort will receive a single intravenous (IV) dose of TN-401. Following Data Safety Monitoring Board (DSMB) review of each dose cohort, the next dose cohort will be initiated. DSMB review will also be needed to expand the dose cohorts. The dose for Cohorts 1/1a will be 3E13 (3 × 1013) vg/kg and the dose for Cohorts 2/2a will be 6E13 (6 × 1013) vg/kg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PKP2 mutation (pathogenic or likely pathogenic)
- •Arrhythmogenic Right Ventricular Cardiomyopathy as defined by the 2010 revised Task Force Criteria
- •Left Ventricular Ejection Fraction ≥50%
- •Functioning Implantable Cardiac Defibrillator with remote integration capabilities at least 9 months prior to Screening
- •NYHA Functional Class I, II, or III
- •Frequent premature ventricular contractions (PVCs)
排除标准
- •Ventricular tachycardia (VT) ablation within 6 months of Screening or planned VT ablation within 6 months after Screening
- •High AAV9 neutralizing antibody titer
- •Prior myocardial infarction
- •Right Ventricular Heart Failure
- •Class IV Heart Failure
- •Clinically significant renal disease
- •Clinically significant liver disease
结局指标
主要结局
Number and severity of Adverse Events over the course of the study.
时间窗: 52 weeks
Number of Serious Adverse Events related to study drug.
时间窗: 5 years
次要结局
- To assess frequency of ICD therapy administration(Week 52)
- To assess frequency of sustained VT(Week 52)
- To assess changes in daily PVC and NSVT counts(Week 52)
研究者
研究点 (14)
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相关资讯
FDA Grants RMAT Designation to Tenaya's TN-401 Gene Therapy for PKP2-Associated ARVC- The FDA granted Regenerative Medicine Advanced Therapy designation to TN-401, Tenaya Therapeutics' AAV9-based gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy.
- The designation was supported by interim RIDGE-1 Phase 1b/2 data showing reduced daily rates of premature ventricular contractions and non-sustained ventricular tachycardias after a single infusion.
- TN-401 already holds FDA Orphan Drug and Fast Track designations plus European Medicines Agency PRIME designation, and Tenaya plans a pivotal trial.
- Tenaya expects to report additional RIDGE-1 data and provide an update on regulatory discussions regarding pivotal trial plans in the fourth quarter of 2026.11 hours agoTenaya Therapeutics Doses First Patient in Phase 1b Trial of TN-401 Gene Therapy for ARVC• Tenaya Therapeutics has dosed the first patient in the RIDGE-1 Phase 1b trial evaluating TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC).
• TN-401 is an AAV9-based gene therapy designed to deliver a functional copy of the PKP2 gene directly to heart cells, addressing the underlying genetic cause of ARVC.
• The RIDGE-1 trial is a multicenter study enrolling approximately 15 patients with ARVC across sites in the US, UK, and Europe, with initial data expected next year.
• Preclinical data demonstrated TN-401's ability to normalize heart rhythms, reverse disease progression, and extend survival in animal models, supporting its clinical development.last year