Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

Phase 1

Active, not recruiting

• Conditions: Friedreich Ataxia; Cardiomyopathy, Secondary
• Interventions: Genetic: Low dose LX2006; Genetic: Mid Dose LX2006; Genetic: High Dose LX2006

• Registration Number: NCT05445323
• Lead Sponsor: Lexeo Therapeutics

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-06-23
• Study First Submitted QC: 2022-06-30
• Study First Posted: 2022-07-06
• Study Start: 2022-08-24
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-13
• Last Update Posted: 2024-11-15
• Primary Completion: 2029-09
• Study Completion: 2029-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 8

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1/ Cohort 2/ Cohort 3	High Dose LX2006	-
Cohort 1/ Cohort 2/ Cohort 3	Mid Dose LX2006	-
Cohort 1/ Cohort 2/ Cohort 3	Low dose LX2006	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Change from baseline in LVMi	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
Change from baseline in LVEF	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
Presence and severity of cardiac arrythmias	Change from baseline to end of year 5 post dose

Trial Locations

Locations (3)

Ataxia Center and HD Center of Excellence, University of California; 🇺🇸 Los Angeles, California, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States