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

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

ArmDescriptionAssigned Intervention
Experimental
Cohort 1 (≥ 18 years of age)
Participants will receive a single intravenous (IV) infusion (dose 1) of SGT-501.
  • Drug: SGT-501
    IV for infusion
Experimental
Cohort 2 (≥ 18 years of age)
Participants will receive a single IV infusion (dose 2) of SGT-501.
  • Drug: SGT-501
    IV for infusion
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.
  • Drug: SGT-501
    IV for infusion

Recruiting Locations

Boston Children's Hospital
Boston, Massachusetts 02459
Contact:
Elizabeth DeWitt, MD
gene.therapy@childrens.harvard.edu

Mayo Clinic
Rochester, Minnesota 55905
Contact:
Kolawole Olarinoye
507-293-1564
Olarinoye.Kolawole@mayo.edu

Cleveland Clinic
Cleveland, Ohio 44195
Contact:
Paige Ewing
216-445-8798
ewingp@ccf.org

More Details

Status
Recruiting
Sponsor
Solid Biosciences Inc.

Study Contact

Solid Bio Clinical Trials
617-337-4680
clinicaltrials@solidbio.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.