Open-label, Dose Escalation Study of Safety and Preliminary Efficacy of TN-401 in Adults With PKP2 Mutation-associated ARVC
Purpose
This first-in-human study is designed to evaluate the safety, and preliminary efficacy (PD) of TN-401 gene therapy in adult patients with symptomatic PKP2 mutation-associated ARVC.
Condition
- Arrhythmogenic Right Ventricular Cardiomyopathy
Eligibility
- Eligible Ages
- Between 18 Years and 65 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- PKP2 mutation (pathogenic or likely pathogenic) - Arrhythmogenic Right Ventricular Cardiomyopathy as defined by the 2010 revised Task Force Criteria - Left Ventricular Ejection Fraction ≥50% - Functioning Implantable Cardiac Defibrillator with remote integration capabilities at least 9 months prior to Screening - NYHA Functional Class I, II, or III - Frequent premature ventricular contractions (PVCs)
Exclusion Criteria
- Ventricular tachycardia (VT) ablation within 6 months of Screening or planned VT ablation within 6 months after Screening - High AAV9 neutralizing antibody titer - Prior myocardial infarction - Right Ventricular Heart Failure - Class IV Heart Failure - Clinically significant renal disease - Clinically significant liver disease
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Cohort 1 |
Dose for Cohort 1 will be 3E13 vg/kg |
|
|
Experimental Cohort 2 |
Dose for Cohort 2 will be 6E13 vg/kg |
|
Recruiting Locations
Brigham and Women's Hospital
Boston, Massachusetts 02115
Boston, Massachusetts 02115
Contact:
Neal Lakdawala, MD
Neal Lakdawala, MD
More Details
- Status
- Recruiting
- Sponsor
- Tenaya Therapeutics
Detailed Description
The RIDGE-1™ open-label Safety, Tolerability, Dose-finding, PD and Cardiac Transgene Expression Study will enroll up to 15 patients in two planned dose cohorts. Patients in each cohort will receive a single intravenous (IV) dose of TN-401. Following Data Safety Monitoring Board (DSMB) review of each dose cohort, the next dose cohort will be initiated. DSMB review will also be needed to expand the dose cohorts. The dose for Cohorts 1/1a will be 3E13 (3 × 1013) vg/kg and the dose for Cohorts 2/2a will be 6E13 (6 × 1013) vg/kg.