A Phase 1b, Multicenter, Open-Label, Dose Finding Study to Investigate the Safety and Tolerability of a Single Intravenous Dose of SGT-501 in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 6
- 主要终点
- Number of Participants with Treatment-Emergent Adverse Event (TEAEs)s through Day 360
研究概览
简要总结
This is a Phase 1b, Multicenter, Open-Label, Dose Finding Study to Investigate the Safety and Tolerability of a Single Intravenous Dose of SGT-501 in participants with catecholaminergic polymorphic ventricular tachycardia (CPVT). The first-in-human (FIH) safety study will focus on obtaining safety data in adult participants. Cohort 1 and Cohort 2 (optional for dose exploration) will include participants ≥ 18 years of age. Cohort 3 will include participants ≥ 7 to < 18 years of age and will be initiated following data and safety monitoring board (DSMB) recommendations. Participants will be monitored for 5 years post-administration of SGT-501 including the active treatment period (1 year) and long-term follow-up (LTFU) (4 years) period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type of Participant and Disease Characteristics:
- •Clinical diagnosis of CPVT, based on documented history of polymorphic or bidirectional non-sustained ventricular tachycardia with exercise or ventricular ectopy in a pattern consistent with CPVT on EST.
- •Central Screening laboratory determination of a RYR2 variant that is pathogenic or likely pathogenic for CPVT.
- •Documented history of life-threatening ventricular arrhythmic event defined as: survived sudden cardiac arrest, sudden cardiac arrest with appropriate implantable cardioverter defibrillator (ICD) shock, arrhythmic syncope, or sustained ventricular tachycardia (30 seconds or more) with or without ICD shock.
- •On stable dose (defined as no change in dose by more than 50% for at least 1 month prior to Screening) of standard-of-care therapy defined as a beta-blocker and/or flecainide.
- •Documented prior history of EST demonstrating a ventricular arrythmia score (VAS) score of ≥
- •For the first 2 participants in each cohort only: a properly functioning ICD device in place. Following review of data from Cohorts 1 and 2, the Data Safety and Monitoring Board (DSMB) will determine if this criterion is required for participants in Cohort
- •Must be up to date with meningococcal vaccination per national guidelines or willing to receive meningococcal vaccine to achieve this.
- •Other inclusion criteria to be applied as per protocol.
排除标准
- •Abnormal liver function: gamma-glutamyl transferase (GGT) > 1.5 × upper limit of normal [ULN] or total bilirubin > ULN).
- •Abnormal renal function defined by estimated glomerular filtration rate < 60 milliliter /minute (mL/min)/1.73-square meter (m^2) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Formula.
- •Clinically significant abnormalities of coagulation including international normalized ratio or activated partial thromboplastin time > 1.2 × ULN or platelets < 150,000 cells/cubic millimeter (mm^3).
- •Potential concomitant cardiomyopathy or inherited arrhythmia as evidenced by pathogenic or likely pathogenic mutation other than RYR2 obtained on cardiac panel during Screening.
- •Current or prior treatment with an approved or investigational gene transfer drug.
- •Exposure to another investigational drug within 90 days prior to Screening or 5 half-lives since last administration, whichever is longer.
- •Contraindication or unwillingness to receive required immunosuppression regimen.
- •Body mass index ≥ 30 kilograms per square meter (kg/m^2).
- •Other exclusion criteria to be applied as per protocol.
研究组 & 干预措施
Cohort 3 (≥ 7 to < 18 years)
Participants will receive a single IV infusion (level at or below dose(s) assessed in adults) of SGT-501.
干预措施: SGT-501 (Drug)
Cohort 1 (≥ 18 years of age)
Participants will receive a single intravenous (IV) infusion (dose 1) of SGT-501.
干预措施: SGT-501 (Drug)
Cohort 2 (≥ 18 years of age)
Participants will receive a single IV infusion (dose 2) of SGT-501.
干预措施: SGT-501 (Drug)
结局指标
主要结局
Number of Participants with Treatment-Emergent Adverse Event (TEAEs)s through Day 360
时间窗: First dose through Day 360
次要结局
- Change from baseline in ventricular arrhythmia score (VAS) on exercise stress test (EST) at Day 180(Baseline, Day 180)