Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

Friedreich Ataxia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05445323
• Other study ID #: LX2006-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 24, 2022
• Est. completion date: September 2029

Study information

• Verified date: May 2024
• Source: Lexeo Therapeutics
• Contact: LEXEO Clinical Trials
• Phone: 212-547-9879
• Email: clinicaltrials[@]lexeotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: September 2029
• Est. primary completion date: September 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ataxia
• Cardiomyopathies
• Cardiomyopathy, Secondary
• Cerebellar Ataxia
• Friedreich Ataxia

Intervention

Genetic:
• Low dose LX2006
Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)
• Mid Dose LX2006
Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)
• High Dose LX2006
Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)

Locations

Country	Name	City	State
Canada	Centre hospitalier de l Universite de Montreal (CHUM)	Montréal	Quebec
United States	University of Iowa	Iowa City	Iowa
United States	Ataxia Center and HD Center of Excellence, University of California	Los Angeles	California
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Lexeo Therapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-emergent adverse events (TEAEs) and Treatment-emergent serious events (TESAEs)		Change from baseline to end of year 5 post dose
Secondary	Change from baseline in LVMi		Change from baseline to end of year 5 post dose
Secondary	Change from baseline in LVEF		Change from baseline to end of year 5 post dose
Secondary	Change from baseline in cardiac fibrosis as measured by cardiac MRI		Change from baseline to end of year 5 post dose
Secondary	Change from baseline in measures of cardiopulmonary exercise tolerance		Change from baseline to end of year 5 post dose
Secondary	Presence and severity of cardiac arrythmias		Change from baseline to end of year 5 post dose