Gene Therapy for ACM Due to a PKP2 Pathogenic Variant

Sponsor

Lexeo Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06109181

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a Phase 1/2, first-in-human, open-label, intravenous, dose-escalating, multicenter trial that is designed to assess the safety and tolerability of LX2020 in adult patients with PKP2-ACM

Condition or Disease	Intervention/Treatment	Phase
Arrhythmogenic Cardiomyopathy PKP2-ACM PKP2-ARVC	Genetic: LX2020	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Study of the Safety and Efficacy of LX2020 Gene Therapy in Patients With Arrhythmogenic Cardiomyopathy Due to a Plakophilin-2 Pathogenic Variant

Anticipated Study Start Date :

Dec 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LX2020 Single ascending dose of LX2020, with a starting dose of 2.0 x10^13 gc/kg, in multiple cohorts	Genetic: LX2020 LX2020 is an adeno-associated viral vector encoding the human Plakophilin-2 (PKP2) gene (AAVrh.10hPKP2)

Arm

Intervention/Treatment

Experimental: LX2020

Single ascending dose of LX2020, with a starting dose of 2.0 x10^13 gc/kg, in multiple cohorts

Genetic: LX2020

LX2020 is an adeno-associated viral vector encoding the human Plakophilin-2 (PKP2) gene (AAVrh.10hPKP2)

Outcome Measures

Primary Outcome Measures

Safety and Tolerability of LX2020 [12 months]
Percentage of subjects who experienced at least 1 treatment emergent adverse event (TEAE) and/or 1 treatment emergent serious adverse event (TESAE).

Other Outcome Measures

Selected Exploratory [12 months]
Change in the frequency of ventricular arrhythmias from baseline.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Selected Inclusion Criteria:

Adults with a clinical diagnosis of ACM meeting the 2010 revised Task Force Criteria (TFC)
Genetic testing documenting a pathogenic or likely pathogenic variant in PKP2
Frequent premature ventricular complexes (PVCs)
Implantable cardioverter-defibrillator (ICD) implantation ≥ 12 weeks prior to consent
Left ventricular ejection fraction ≥ 50%