Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

Lexeo Therapeutics

Status and phase

Active, not recruiting

Phase 2

Phase 1

Conditions

Cardiomyopathy, Secondary

Friedreich Ataxia

Treatments

Genetic: Low dose LX2006

Genetic: High Dose LX2006

Genetic: Mid Dose LX2006

Study type

Interventional

Funder types

Industry

Identifiers

NCT05445323

LX2006-01

Details and patient eligibility

About

This is a Phase 1/2, open-label, dose-ascending, multicenter study of the safety and efficacy of LX2006 for participants who have Friedreich's Ataxia with evidence of cardiomyopathy. The study will evaluate up to three doses of single administration of LX2006 (AAVrh.10hFXN), an adeno-associated virus (AAV) gene therapy designed to intravenously deliver the human frataxin (hFXN) gene to cardiac cells over a 52-week period. Long-term safety and efficacy will be evaluated for an additional 4-years for a total of 5-years post LX2006 treatment.

Full description

Friedreich's ataxia (FA) is a rare, autosomal recessive disease caused by a mutation in the autosomal frataxin (FXN) gene. Progressive cardiomyopathy with cardiac hypertrophy and fibrosis is observed in most individuals with FA. The disease is more severe in those with earlier onset. Presently, there is no therapy that alters the progression of cardiomyopathy in FA, which is responsible for 59% of FA-related deaths.

The primary objective of this dose escalation study is to assess the safety and tolerability of three ascending doses of LX2006 in patients with FA-associated cardiomyopathy. LX2006 is designed to restore hFXN levels in order to improve mitochondrial function. Assessments of cardiac function, biomarkers and other preliminary efficacy endpoints are also included in this study.

Enrollment

8 patients

Sex

All

Ages

18 to 50 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Confirmed genetic diagnosis of FA, with onset being before 25 years of age
Protocol specified ranges for antibodies
Protocol specified measures of FA cardiomyopathy

Exclusion criteria

Protocol specified ranges for left ventricular ejection fraction (LVEF) as measured by cardiac ECHO
Uncontrolled diabetes
Abnormal liver function
Active infection of any type, including hepatitis virus (A, B or C) or human immunodeficiency virus (HIV-1 and HIV-2)
Contraindication to cardiac MRI
Contraindications to cardiac biopsies
Participants who are receiving systemic corticosteroids or other immunosuppressive medications
History of significant coronary artery disease or any structural heart or vascular disease other than FA cardiomyopathy
Presence of clinically significant, hemodynamically unstable arrhythmias, requiring physician intervention
Presence of clinically significant abnormalities as determined by the investigator, other than ECG abnormalities related to FA
Uncontrolled psychiatric disease