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

ConditionsFriedreich AtaxiaCardiomyopathiesCardiac HypertrophyMyocardial Fibrosis
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12-50
SponsorWeill Medical College of Cornell University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Individuals receiving corticosteroids or other immunosuppressive medications

Individuals with uncontrolled diabetes (glycated hemoglobin, HbA1c levels >7%)

Genotype FA missense mutation on one or both alleles

Evidence of infection defined by elevated white blood cell count, temperature >38.5̊ C, infiltrate on chest x-ray

Trial design

Design model

Sequential

Treatments tested in this trial

  • AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN

    Biological/Vaccine

    AAVrh.10hFXN will be administered intravenously.

  • Prednisone

    Drug

    All participants will remain immunosuppression therapy with prednisone for a total of 14 weeks.

Treatment groups

25 Participants
are divided into 4 treatment groups
Group A: First Dose CohortExperimental treatment 2 interventions
Group B: Second Dose CohortExperimental treatment 2 interventions
Group C: Third Dose CohortExperimental treatment 2 interventions
Group D: Maximum Tolerated Dose CohortExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Safety of AAVrh.10hFXN

To determine the safety of AAVrh.10hFXN, as measured by the number of subjects with any treatment-related adverse events for 5 years.

Time frame
5 Years

Secondary outcomes

Other outcomes

1

Change in cardiopulmonary exercise testing

To determine changes in parameters of cardiopulmonary testing (measured by the change in VO2max), from screening (pre-treatment) to up to 5 years post administration.

Time frame
5 Years
2

Change in cardiac-relevant parameters in cardiac-magnetic resonance scans

To determine if there are changes in parameters of cardiac imaging (including Left Ventricular mass, Left Ventricular stroke volume, Global longitudinal strain and wall thickness), from screening (pre-treatment) to up to 5 years post administration.

Time frame
5 Years
3

Change in cardiac-relevant parameters in echocardiograms

To determine if there are changes in parameters of echocardiograms (including left ventricle mass, Wall thickness and Left ventricle ejection fraction), from screening (pre-treatment) to up to 5 years post administration.

Time frame
5 Years
4

Change in arrhythmias with 24-hour monitoring.

To determine if there are changes in heart arrhythmias, from screening (pre-treatment) to up to 5 years post administration. This will be measure by holter monitoring.

Time frame
5 Years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Weill Medical College of Cornell University

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Source ClinicalTrials.gov
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