Cardiomyopathy, Secondary, Friedreich Ataxia
Conditions
Keywords
Friedreich's Ataxia, Cardiomyopathy, FA, Gene therapy, FXN Gene, Frataxin Gene, LX2006
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.
Interventions
GENETICLow dose LX2006
Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)
GENETICMid Dose LX2006
Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)
GENETICHigh Dose LX2006
Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)
Sponsors
Lexeo Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| 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
| 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 |
| 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 |
Countries
United States
Outcome results
None listed