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.
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
- Conditions the study is for
- Friedreich Ataxia, Cardiomyopathies, Cardiac Hypertrophy
- 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
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.
United States1 site, 1 recruiting
- 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
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 group | Role | What they receive |
|---|---|---|
| First Dose Cohort | Experimental | AAVrh.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 Cohort | Experimental | AAVrh.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 Cohort | Experimental | AAVrh.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 Cohort | Experimental | AAVrh.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.
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.
- First posted31 Mar 2022
- Study start22 Feb 2022
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Friedreich AtaxiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Ronald G Crystal, MD, Principal investigator, Weill Medical College of Cornell University
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 42307907Hendrickx 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 40739200De 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