Inclusion Criteria:

• Participant’s age at the time of informed consent/assent:
  • Cohorts 1 and 2: ≥ 18 years
  • Cohort 3: ≥ 7 to < 18 years
• Clinical diagnosis of CPVT, based on the following:
  • 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 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 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 DSMB will determine if this criterion is required for participants in Cohort 3.
• If participant is of reproductive potential, participant and partner of childbearing potential are willing to use 2 highly effective forms of contraception for 12 months following administration of SGT-501.
• Able to understand and comply with all study procedures as appropriate by age and have a parent(s) or legal guardian(s) (i.e., legally authorized representative [LAR]) who is (are) able to understand and comply with the study procedure requirements. Medical Monitor approval required for entry if the participant is not able to understand and comply with any study procedures due to age. Be willing to provide informed assent and have an LAR(s) who is (are) willing to provide written informed consent for the participant to participate in the study.

Exclusion Criteria:

• Any prior or ongoing medical condition, medical history, or physical finding that, in the Investigator's opinion, could adversely affect the safety of the participant, make it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
• Poorly controlled diabetes mellitus, defined as a hemoglobin A1C > 8%.
• 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 mL/min/1.73 m2 using 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/mm3 .
• Anatomic, pulmonary, or other impairments that would prevent the performance of an EST.
• Documented or suspected history of epicardial coronary artery disease (> 70% stenosis of a major epicardial coronary artery or > 50% stenosis of the left main coronary artery).
• Structurally abnormal heart including more than mildly increased right or left ventricular chamber sizes, mild left ventricular hypertrophy, or left ventricular ejection fraction < 50% or evidence of left ventricular non-compaction at Screening.
• History or current cardiac ventricular arrhythmia independent of CPVT.
• More than mild mitral, pulmonic, or aortic valve stenosis or regurgitation.
• Uncorrected hemodynamically significant cardiac shunt.
• Have severe hypersensitivity reactions, including anaphylaxis, to SGT-501 or its components.
• Potential concomitant cardiomyopathy or inherited arrhythmia as evidenced by pathogenic or likely pathogenic mutation other than RYR2 obtained on cardiac panel during Screening.
• History of malignancy within the past 5 years prior to Screening, with the exception of successfully treated basal cell carcinoma or non-metastatic squamous cell carcinoma or skin or cervical carcinoma in situ.
• 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.
• Recent or planned major surgery that would interfere with the ability to perform planned ESTs.
• Vaughan Williams Class III and IV medicines.
• Planned sympathectomy in the 12 months following dosing.
• Body mass index ≥ 30 kg/m2 .
• Sponsor employees and their family members are ineligible to participate in this study.
• Positive for pre-existing anti-AAV8 antibodies.
• Participant is pregnant or breast-feeding.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 03/10/2025. Questions regarding updates should be directed to the study team contact.