Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

A Phase 1/2 Study of the Safety and Efficacy of LX2006 Gene Therapy in Participants With Cardiomyopathy Associated With Friedreich's Ataxia

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.

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.

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

Other Inclusion/Exclusion criteria to be applied as per protocol.