Arrhythmias Clinical Trials

⁃ 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.