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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 : December 5, 2022
Sponsor:
Information provided by (Responsible Party):
Lexeo Therapeutics

Tracking Information
First Submitted Date  ICMJE June 23, 2022
First Posted Date  ICMJE July 6, 2022
Last Update Posted Date December 5, 2022
Actual Study Start Date  ICMJE August 24, 2022
Estimated Primary Completion Date September 2029   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2022)
Treatment-emergent adverse events (TEAEs) and Treatment-emergent serious events (TESAEs) [ Time Frame: Change from baseline to end of year 5 post dose ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2022)
  • Change from baseline in peak VO2 [ Time Frame: Change from baseline to end of year 5 post dose ]
  • Change from baseline in LVMi [ Time Frame: Change from baseline to end of year 5 post dose ]
  • Change from baseline in LVEF [ Time Frame: Change from baseline to end of year 5 post dose ]
  • Change from baseline in cardiac fibrosis as measured by cardiac MRI [ Time Frame: Change from baseline to end of year 5 post dose ]
  • Presence and severity of cardiac arrythmias [ Time Frame: Change from baseline to end of year 5 post dose ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia
Official Title  ICMJE A Phase 1/2 Study of the Safety and Efficacy of LX2006 Gene Therapy in Participants With Cardiomyopathy Associated With Friedreich's Ataxia
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Friedreich Ataxia
  • Cardiomyopathy, Secondary
Intervention  ICMJE
  • 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)
Study Arms  ICMJE Experimental: Cohort 1/ Cohort 2
Interventions:
  • Genetic: Low dose LX2006
  • Genetic: High Dose LX2006
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 30, 2022)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2029
Estimated Primary Completion Date September 2029   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 focal fibrosis on cardiac MRI
  • Protocol specified ranges for stroke volume index and 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: LEXEO Clinical Trials 212-547-9879 clinicaltrials@lexeotx.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05445323
Other Study ID Numbers  ICMJE LX2006-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Lexeo Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Lexeo Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: LEXEO Clinical Trials Lexeo Therapeutics
PRS Account Lexeo Therapeutics
Verification Date December 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP