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Friedreich AtaxiaPhase 1NCT05302271

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

A Phase 1 study testing AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN and Prednisone in people with Friedreich Ataxia and Cardiomyopathies, run by Weill Medical College of Cornell University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 12 to 50 years
What is being tested?
AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN and Prednisone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
22 Feb 2022to 31 Dec 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 50 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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%
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  • 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

Who cannot join

  • 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
  • Decompensated heart failure (NY4A class III-IV at time of baseline clinical assessment)
  • Hemoglobin <10 g/dl
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  • Absolute neutrophil count <1500 cells/mm3
  • Platelet count <100,000 cells/mm3
  • 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)
  • 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
  • Use of oxygen supplementation
  • 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 uncontrolled psychiatric disease
  • Pregnant or breastfeeding woman
  • 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)
  • Any lung function abnormalities that would affect cardiopulmonary testing
  • 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
  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Maddie Galbraith, BS contact

646-962-2672

meg4013@med.cornell.edu

Niamh Savage, BS contact

646-962-5527

nis2049@med.cornell.edu

United States1 site, 1 recruiting

  • Weill Cornell Medicine

    New York, New York, 10021

    Maddie Galbraith, BS, 646-962-2672, meg4013@med.cornell.edu

    Niamh Savage, BS, 646-962-5527, nis2049@med.cornell.edu

    Recruiting

Other trials in United States

About this study

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.

Being tested
AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN, Prednisone
Keywords
Ataxia, Friedreich's ataxia, Pediatric, Gene therapy
Medical subject headings
Friedreich Ataxia, Cardiomyopathies, Cardiomegaly, Ataxia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    AAVrh.10hFXN will be administered intravenously.

  • PrednisoneDrug

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

Study groups in NCT05302271
Study groupRoleWhat they receive
First Dose CohortExperimentalAAVrh.10hFXN will be administered intravenously.
Receives: Biological: AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN; Drug: Prednisone
Second Dose CohortExperimentalAAVrh.10hFXN will be administered intravenously.
Receives: Biological: AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN; Drug: Prednisone
Third Dose CohortExperimentalAAVrh.10hFXN will be administered intravenously.
Receives: Biological: AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN; Drug: Prednisone
Maximum Tolerated Dose CohortExperimentalAAVrh.10hFXN will be administered intravenously.
Receives: Biological: AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 5 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Mar 2022
  2. Study start22 Feb 2022
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
The clinical study design is a dose-escalation study with 4 cohorts of n=25, 5 subjects at each of 3 doses to establish the safety of the investigational drug product, and 1 cohort with n=10 at the maximum tolerated dose. The vector will be delivered intravenously.
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05302271
Sponsor's protocol ID
20-01021274
Other IDs
R61HL151355
Status last verified
Sep 2026
First submitted
21 Mar 2022
Last updated
28 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Crystal RG, Weinsaft JW, Kaminsky SM, Caragiulo A, Savage N, Patel A, Gavrilova RH, Perlman SL, Galbraith M, Kahlon U, Krishnan U, Kaner RJ, Sanders A, Vo M, Sarva H, Yoo A, Sondhi D, De BP, Mezey JG, Aubert G, Khan A, Selvan N, Bhalla N, Adler E, Zesiewicz T. AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich Ataxia: A Nonrandomized Clinical Trial. JAMA Cardiol. 2026 Aug 1;11(8):709-718. doi: 10.1001/jamacardio.2026.1699.

    PubMed 42307907

  • Hendrickx N, Mentre F, Hamdan A, Karlsson MO, Hooker AC, Traschutz A, Gagnon C, Schule R, Synofzik M, Comets E; ARCA Study Group, EVIDENCE-RND consortium. Comparing randomized trial designs to estimate treatment effect in rare diseases with longitudinal models: a simulation study showcased by Autosomal Recessive Cerebellar Ataxias using the SARA score. BMC Med Res Methodol. 2025 Jul 30;25(1):179. doi: 10.1186/s12874-025-02626-x.

    PubMed 40739200

  • De BP, Cram S, Lee H, Rosenberg JB, Sondhi D, Crystal RG, Kaminsky SM. Assessment of Residual Full-Length SV40 Large T Antigen in Clinical-Grade Adeno-Associated Virus Vectors Produced in 293T Cells. Hum Gene Ther. 2023 Aug;34(15-16):697-704. doi: 10.1089/hum.2023.032.

    PubMed 37171121

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXN and Prednisone in people with Friedreich Ataxia and Cardiomyopathies, run by Weill Medical College of Cornell University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Maddie Galbraith, BS (646-962-2672, meg4013@med.cornell.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of AAVrh.10hFXN (time frame: 5 Years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05302271, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.

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