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.

Study Overview

• Status: Active, not recruiting
• Conditions: Friedreich Ataxia; Cardiomyopathy, Secondary
• Intervention / Treatment: Genetic: Low dose LX2006; Genetic: High Dose LX2006; Genetic: Mid Dose LX2006

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Ataxia Center and HD Center of Excellence, University of California
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1/ Cohort 2/ Cohort 3	Genetic: Low dose LX2006; Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN); Genetic: High Dose LX2006; Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN); Genetic: Mid Dose LX2006; Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Treatment-emergent adverse events (TEAEs) and Treatment-emergent serious events (TESAEs)	Change from baseline to end of year 5 post dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in LVMi	Change from baseline to end of year 5 post dose
Change from baseline in LVEF	Change from baseline to end of year 5 post dose
Change from baseline in cardiac fibrosis as measured by cardiac MRI	Change from baseline to end of year 5 post dose
Presence and severity of cardiac arrythmias	Change from baseline to end of year 5 post dose
Change from baseline in measures of cardiopulmonary exercise tolerance	Change from baseline to end of year 5 post dose

Collaborators and Investigators

• Sponsor: Lexeo Therapeutics
• Investigators: Study Director: Lexeo Clinical Trials, Lexeo Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Estimated): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Cardiomyopathy; Gene therapy; Friedreich's Ataxia; FA; FXN Gene; Frataxin Gene; LX2006
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cardiovascular Diseases; Heart Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Mitochondrial Diseases; Cerebellar Diseases; Spinocerebellar Degenerations; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Cardiomyopathies; Friedreich Ataxia
• Other Study ID Numbers: LX2006-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No