Clinical trial NCT05445323: Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Friedreich Ataxia
Cardiomyopathy, Secondary
Keywords: Friedreich's Ataxia
Cardiomyopathy
FA
Gene therapy
FXN Gene
Frataxin Gene
LX2006
Lead sponsor: Lexeo Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-07-06
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment-emergent adverse events (TEAEs) and Treatment-emergent serious events (TESAEs)
timeFrame: Change from baseline to end of year 5 post dose
Secondary outcomes:
measure: Change from baseline in LVMi
timeFrame: Change from baseline to end of year 5 post dose
measure: Change from baseline in LVEF
timeFrame: Change from baseline to end of year 5 post dose
measure: Change from baseline in cardiac fibrosis as measured by cardiac MRI
timeFrame: Change from baseline to end of year 5 post dose
measure: Change from baseline in measures of cardiopulmonary exercise tolerance
timeFrame: Change from baseline to end of year 5 post dose
measure: Presence and severity of cardiac arrythmias
timeFrame: Change from baseline to end of year 5 post dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ataxia Center and HD Center of Excellence, University of California
state: California
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Lexeo Therapeutics
name: LEXEO Clinical Trials
role: STUDY_DIRECTOR
References: