Gene Therapy Tested for Heart Disease in Friedreich Ataxia

Trial details

Who runs it

Weill Medical College of Cornell University

Trial code

NCT05302271

Record updated

28 September 2026

Original description

The purpose of this study is to test the safety and preliminary efficacy of AAVrh.10hFXN to treat the cardiomyopathy associated with Friedreich's ataxia (FA). AAVrh.10hFXN is a serotype rh.10 adeno-associated virus gene transfer vector coding for Frataxin (FXN). The drug is administered intravenously. This is a phase 1, open label, dose escalation study with a total of 25 participants.Read full original descriptionShow less

Phase IA and IB Study of AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich's Ataxia

The purpose of this study is to test the safety and preliminary efficacy of AAVrh.10hFXN to treat the cardiomyopathy associated with Friedreich's ataxia (FA). AAVrh.10hFXN is a serotype rh.10 adeno-associated virus gene transfer vector coding for Frataxin (FXN). The drug is administered intravenously. This is a phase 1, open label, dose escalation study with a total of 25 participants.

Inclusion: Males and females, age 12 to 50; Willing and able to provide informed consent; Definitive diagnosis of FA, based on clinical phenotype and genotype (GAA expansion on both alleles); >600 GAA repeats in intron 1 in at least one allele; FARS and SARA neurologic scores consistent with diagnosis of Friedreich's ataxia; Left ventricle ejection fraction (EF) measured by cardiac MRI of ≥35% to 75%; Evidence of FA-related cardiac disease that falls into one of the 2 categories: Early disease (defined by serum high sensitivity troponin above the normal range, without increased LVMI) or Advanced disease (defined as high sensitivity troponin above the normal range and increased LVMI); Increased LVMI in adults: In the absence of other factors known to cause left ventricular hypertrophy, cardiac MRI left ventricular mass index >2 standard deviations above the normal range (males >84 gm/m², females >69 gm/m²); Increased LVMI in pediatrics: In the absence of other factors known to cause left ventricular hypertrophy, cardiac MRI left ventricular mass index >95ᵗʰ centile based on normal BSA for their age and gender; Fibrosis ≤10% in the left ventricular wall on late gadolinium enhancement cardiac MRI; Resting O2 saturation ≥95%; Serum neutralizing anti-AAVrh.10 titer <1:125; Hematocrit >30%; White blood cell levels within normal limits; Normal prothrombin, partial thromboplastin time; Normal liver-related serum parameters (ALT, AST, ALP, bilirubin); normal liver ultrasound and serum alpha fetoprotein; Normal kidney function as assessed by plasma urea and creatinine; estimated GFR >30 mL/min/1.73m²; No evidence of active infection of any types, including hepatitis virus (A, B or C), human immunodeficiency virus (HIV-1 and HIV-2), or SARS-CoV2; Fertile individuals should utilize barrier birth control measures to prevent pregnancy for up to 6 months after vector administration; Individuals not receiving experimental medications or participating in another experimental protocol for at least 12 wk prior to entry to the study (individuals who are/have received approved therapy will be included); Capable of undergoing cardiac MRI; No contraindications to receiving corticosteroid immunosuppression.

Exclusion: Individuals receiving corticosteroids or other immunosuppressive medications; Concomitant conditions (other than FA) known to produce left ventricular hypertrophy, including aortic stenosis, systemic hypertension (BP ≥140/90 on noninvasive blood pressure), or genetically mediated hypertrophic cardiomyopathy; Prior participation in any gene and/or cell therapy; Known obstructive coronary artery disease (as documented by clinical history of myocardial infarction, prior coronary revascularization or angina symptoms (Canadian Cardiovascular Society grade ≥2 at time of baseline clinical assessment), or epicardial obstructive coronary artery disease (≥ 50% left main, ≥ 70% of other major coronary arteries); If prior infection with SARS-CoV2, any related residual cardiac or pulmonary abnormalities; Alcoholism or drug addiction (see reference 71 for alcoholism, reference 72 for drug addiction); Decompensated heart failure (NY4A class III-IV at time of baseline clinical assessment); Hemodynamically unstable atrial or ventricular arrhythmias which require medical intervention; Contraindication to cardiac MRI (e.g., non-MRI compatible pacemaker/defibrillator) or gadolinium (known or suspected hypersensitivity, glomerular filtration rate <30 mL/min/1.73m2); Any malignancy during the last five years, except basal cell skin cancer; Unrelated clinical condition with life expectancy <12 months (prohibiting follow-up); Any uncontrolled psychiatric disease; Individuals with uncontrolled diabetes (glycated hemoglobin, HbA1c levels >7%); Evidence of infection defined by elevated white blood cell count, temperature >38.5̊ C, infiltrate on chest x-ray; Hemoglobin <10 g/dl; Absolute neutrophil count <1500 cells/mm3; Platelet count <100,000 cells/mm3; Risk for thromboembolic disease, including history of thromboembolic disease hospitalization within the last 90 days, recent trauma and/or recent surgical procedure. If the history of thromboembolic disease is not definitive, the subject will be excluded if laboratory testing suggests a risk for thromboembolic disease because of mutations in the protein-S, protein C, antithrombin, factor V Leiden or prothrombin gene; Any condition, disorder, or abnormal laboratory test findings at screening which, in the judgment of the investigator, would interfere with the individual's ability to comply with all study requirements, or would require the administration of treatment during the study that could potentially affect the interpretation of the study data, or would place the individual at an unacceptable risk by his/her participation in the study; Genotype FA missense mutation on one or both alleles; Use of oxygen supplementation; Pregnant or breastfeeding woman; Any lung function abnormalities that would affect cardiopulmonary testing.

ClinicalTrials.gov NCT05302271