A Study of SGT-501 Gene Therapy in Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
Purpose
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.
Condition
- Catecholaminergic Polymorphic Ventricular Tachycardia
Eligibility
- Eligible Ages
- Over 7 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Cohort 1 (≥ 18 years of age) |
Participants will receive a single intravenous (IV) infusion (dose 1) of SGT-501. |
|
|
Experimental Cohort 2 (≥ 18 years of age) |
Participants will receive a single IV infusion (dose 2) of SGT-501. |
|
|
Experimental 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. |
|
Recruiting Locations
Boston, Massachusetts 02459
Rochester, Minnesota 55905
More Details
- Status
- Recruiting
- Sponsor
- Solid Biosciences Inc.