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Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

Primary Purpose

Friedreich Ataxia, Cardiomyopathy, Secondary

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Low dose LX2006

Mid Dose LX2006

High Dose LX2006

About this trial

This is an interventional treatment trial for Friedreich Ataxia focused on measuring Friedreich's Ataxia, Cardiomyopathy, FA, Gene therapy, FXN Gene, Frataxin Gene, LX2006

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Ataxia Center and HD Center of Excellence, University of CaliforniaRecruiting
University of South FloridaRecruiting
University of IowaRecruiting
Mayo ClinicRecruiting
Hospital of the University of Pennsylvania
Centre hospitalier de l Universite de Montreal (CHUM)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cohort 1/ Cohort 2/ Cohort 3

Arm Description

Outcomes

Primary Outcome Measures

Treatment-emergent adverse events (TEAEs) and Treatment-emergent serious events (TESAEs)

Secondary Outcome Measures

Change from baseline in LVMi

Change from baseline in LVEF

Change from baseline in cardiac fibrosis as measured by cardiac MRI

Change from baseline in measures of cardiopulmonary exercise tolerance

Presence and severity of cardiac arrythmias

Full Information

NCT ID

NCT05445323

First Posted

June 23, 2022

Last Updated

August 29, 2023

Sponsor

Lexeo Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT05445323

Brief Title

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 24, 2022 (Actual)

Primary Completion Date

September 2029 (Anticipated)

Study Completion Date

September 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lexeo Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Friedreich Ataxia, Cardiomyopathy, Secondary

Keywords

Friedreich's Ataxia, Cardiomyopathy, FA, Gene therapy, FXN Gene, Frataxin Gene, LX2006

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1/ Cohort 2/ Cohort 3

Arm Type

Experimental

Intervention Type

Genetic

Intervention Name(s)

Low dose LX2006

Intervention Description

Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)

Intervention Type

Genetic

Intervention Name(s)

Mid Dose LX2006

Intervention Description

Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)

Intervention Type

Genetic

Intervention Name(s)

High Dose LX2006

Intervention Description

Adeno-associated viral vector encoding the FXN gene (AAVrh.10hFXN)

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

Change from baseline in LVMi

Time Frame

Change from baseline to end of year 5 post dose

Title

Change from baseline in LVEF

Time Frame

Change from baseline to end of year 5 post dose

Title

Change from baseline in cardiac fibrosis as measured by cardiac MRI

Time Frame

Change from baseline to end of year 5 post dose

Title

Change from baseline in measures of cardiopulmonary exercise tolerance

Time Frame

Change from baseline to end of year 5 post dose

Title

Presence and severity of cardiac arrythmias

Time Frame

Change from baseline to end of year 5 post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

LEXEO Clinical Trials

Phone

212-547-9879

clinicaltrials@lexeotx.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

LEXEO Clinical Trials

Organizational Affiliation

Lexeo Therapeutics

Official's Role

Study Director

Facility Information:

Facility Name

Ataxia Center and HD Center of Excellence, University of California

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Aaron Fisher

Phone

310-206-8153

adfisher@mednet.ucla.edu

Facility Name

University of South Florida

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lucretia Campbell

Phone

813-974-5633

lcampbel@usf.edu

Facility Name

University of Iowa

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ciara Gibbs

Phone

319-384-9618

ciara-gibbs@uiowa.edu

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Michaela Kolarova

Phone

507-266-7969

kolarova.michaela@mayo.edu

First Name & Middle Initial & Last Name & Degree

Clinical Genomics Research Team

rstcgresearch@mayo.edu

Facility Name

Hospital of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

David Lynch, MD, PhD

Facility Name

Centre hospitalier de l Universite de Montreal (CHUM)

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H2X 0C1

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Antoine Duquette, MD

Phone

514-890-8000

Ext

30737

uit.eligibilite.chum@ssss.gouv.qc.ca

12. IPD Sharing Statement

Plan to Share IPD

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Gene Therapy for Cardiomyopathy Associated With Friedreich's Ataxia

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