SGT-501 gene therapy for RYR2-related CPVT

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

This will test whether a single intravenous dose of SGT-501 is safe and tolerable for people with RYR2-positive CPVT, including adults and children.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 7 Years and up
• Sex: All
• Sponsor: Solid Biosciences Inc. (industry)
• Locations: 5 sites (Boston, Massachusetts and 4 other locations)
• Trial ID: NCT07148089 on ClinicalTrials.gov

What this trial studies

This Phase 1b, first-in-human, multicenter, open-label dose-finding program gives a single IV dose of SGT-501 and follows participants for safety. Adult cohorts are enrolled first with an optional pediatric cohort (ages 7 to <18) initiated after DSMB review. Eligible participants require a pathogenic or likely pathogenic RYR2 variant and a history of life-threatening ventricular arrhythmia while on stable beta-blocker and/or flecainide therapy. Participants undergo an active 1-year monitoring period followed by 4 years of long-term follow-up for safety and durability signals.

Who should consider this trial

Good fit: Ideal candidates are people with a clinical CPVT diagnosis and a pathogenic/likely pathogenic RYR2 variant, a documented history of life-threatening ventricular arrhythmia, and who are on a stable dose of beta-blocker and/or flecainide (adult and qualifying pediatric ages per cohort).

Not a fit: Patients without a pathogenic RYR2 variant, those with milder CPVT without prior severe arrhythmias, or individuals with contraindications to AAV-based gene therapy or to study procedures are unlikely to benefit.

Why it matters

Potential benefit: If successful, SGT-501 could provide a durable genetic therapy that reduces or prevents life-threatening arrhythmias in people with RYR2-related CPVT.

How similar studies have performed: This is the first-in-human gene therapy specifically for CPVT; preclinical RYR2-targeted work showed promise but human efficacy has not been demonstrated.

Eligibility criteria

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.

Where this trial is running

Boston, Massachusetts and 4 other locations

• Boston Children's Hospital — Boston, Massachusetts, United States (RECRUITING)
• Mayo Clinic — Rochester, Minnesota, United States (RECRUITING)
• Cleveland Clinic — Cleveland, Ohio, United States (RECRUITING)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (NOT_YET_RECRUITING)
• St. Paul's Hospital — Vancouver, British Columbia, Canada (RECRUITING)

Study contacts

• Study coordinator: Solid Bio Clinical Trials

Conditions: Catecholaminergic Polymorphic Ventricular Tachycardia, Catecholaminergic polymorphic ventricular tachycardia, SGT-501, Ryanodine Receptor 2, adeno-associated virus serotype 8, Cardiac, Gene Therapy