Summary
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.
Eligibility Criteria
Age Range: 7 years to No maximum
Inclusion Criteria:
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 ≥ 2.
* 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 3.
* 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.
Exclusion Criteria:
* 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.