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Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

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ClinicalTrials.gov Identifier: NCT05445323
Recruitment Status : Recruiting
First Posted : July 6, 2022
Last Update Posted : November 29, 2022
Information provided by (Responsible Party):
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 first portion will evaluate two 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.

Condition or disease Intervention/treatment Phase
Friedreich Ataxia Cardiomyopathy, Secondary Genetic: Low dose LX2006 Genetic: High Dose LX2006 Phase 1 Phase 2

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 60% of FA-related deaths.

The primary objective of this dose-ranging study is to assess the safety and tolerability of two 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 24, 2022
Estimated Primary Completion Date : September 2029
Estimated Study Completion Date : September 2029

Arm Intervention/treatment
Experimental: Cohort 1/ Cohort 2 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)

Primary Outcome Measures :
  1. Treatment-emergent adverse events (TEAEs) and Treatment-emergent serious events (TESAEs) [ Time Frame: Change from baseline to end of year 5 post dose ]

Secondary Outcome Measures :
  1. Change from baseline in peak VO2 [ Time Frame: Change from baseline to end of year 5 post dose ]
  2. Change from baseline in LVMi [ Time Frame: Change from baseline to end of year 5 post dose ]
  3. Change from baseline in LVEF [ Time Frame: Change from baseline to end of year 5 post dose ]
  4. Change from baseline in cardiac fibrosis as measured by cardiac MRI [ Time Frame: Change from baseline to end of year 5 post dose ]
  5. Presence and severity of cardiac arrythmias [ Time Frame: Change from baseline to end of year 5 post dose ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed genetic diagnosis of FA, with onset before 25 years of age
  • No contraindications to cardiac biopsies
  • Normal liver and kidney function
  • Protocol specified ranges for cardiopulmonary exercise testing (CPET) arm ergometry
  • Protocol specified ranges for antibodies
  • Protocol specified ranges for left ventricular ejection fraction (LVEF) as measured by cardiac MRI
  • Protocol specified ranges for left ventricular hypertrophy (LVH) on cardiac MRI, defined as left ventricular mass index (LVMi)
  • Protocol specified ranges for focal fibrosis on cardiac MRI
  • Protocol specified ranges for stroke volume index and/or global longitudinal left ventricular strain on cardiac MRI
  • No evidence of active infection of any type, including hepatitis virus (A, B or C) or human immunodeficiency virus (HIV-1 and HIV-2)

Exclusion Criteria:

  • Uncontrolled diabetes
  • History of clinically significant lung function abnormality
  • Contraindication to cardiac MRI
  • Participants who are receiving systemic corticosteroids or other immunosuppressive medications
  • History of coronary artery disease or any structural heart or vascular disease, including but not limited to aortic stenosis and hypertrophic obstructive cardiomyopathy, other than FA cardiomyopathy
  • History of hemodynamically unstable arrhythmias requiring physician intervention; the 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05445323

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Contact: LEXEO Clinical Trials 212-547-9879 clinicaltrials@lexeotx.com

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United States, California
Ataxia Center and HD Center of Excellence, University of California Recruiting
Los Angeles, California, United States, 90095
Contact: Aaron Fisher    310-206-8153    adfisher@mednet.ucla.edu   
United States, Florida
University of South Florida Recruiting
Tampa, Florida, United States, 33612
Contact: Shaila Ghanekar    813-974-5909    sghanekar@usf.edu   
Contact: Lucretia Campbell    813-974-5633    lcampbel@usf.edu   
United States, Iowa
University of Iowa Not yet recruiting
Iowa City, Iowa, United States, 52242
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Lexeo Therapeutics
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Study Director: LEXEO Clinical Trials Lexeo Therapeutics
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Responsible Party: Lexeo Therapeutics
ClinicalTrials.gov Identifier: NCT05445323    
Other Study ID Numbers: LX2006-01
First Posted: July 6, 2022    Key Record Dates
Last Update Posted: November 29, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Lexeo Therapeutics:
Friedreich's Ataxia
Gene therapy
FXN Gene
Frataxin Gene
Additional relevant MeSH terms:
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Cerebellar Ataxia
Friedreich Ataxia
Heart Diseases
Cardiovascular Diseases
Neurologic Manifestations
Nervous System Diseases
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinocerebellar Degenerations
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases