Open-label, Dose Escalation Study of Safety and Preliminary Efficacy of TN-401 in Adults With PKP2 Mutation-associated ARVC

Официальное название

First-in-Human, Open-Label, Safety, Tolerability, Dose-Finding, Pharmacodynamic and Cardiac Transgene Expression Study of TN-401, a Recombinant Adeno-associated Virus Serotype 9 (AAV9) Containing Plakophilin-2 (PKP2) Transgene, in Adults With PKP2 Mutation-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

Обзор

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.

Подробное описание

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.

Вмешательства

• Генная терапия TN-401
  TN-401 is a recombinant adeno-associated virus serotype 9 (AAV9) gene therapy containing Plakophilin-2 (PKP2) transgene. It is a single (one-time) intravenous dose.

Первичные конечные точки

• Number and severity of Adverse Events over the course of the study. [Срок оценки: 52 weeks]
• Number of Serious Adverse Events related to study drug. [Срок оценки: 5 years]

Вторичные конечные точки (3)

• To assess changes in daily PVC and NSVT counts [Срок оценки: Week 52]
• To assess frequency of ICD therapy administration [Срок оценки: Week 52]
• To assess frequency of sustained VT [Срок оценки: Week 52]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 7 центров

• University of California San Francisco — San Francisco
• University of Colorado - Anschutz Medical Campus — Aurora
• Johns Hopkins University — Baltimore
• Brigham and Women's Hospital — Boston
• Mayo Clinic — Rochester
• NYU Langone Health — New York
• Cleveland Clinic — Cleveland

Идентификаторы

NCT: NCT06228924 · TN-401-0012

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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