NCT05302271

Brief 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. This is a phase 1, open label, dose escalation study with a total of 25 participants.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1

Timeline
44mo left

Started Feb 2022

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress55%
Feb 2022Dec 2029

Study Start

First participant enrolled

February 22, 2022

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

March 21, 2022

Completed
10 days until next milestone

First Posted

Study publicly available on registry

March 31, 2022

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2028

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2029

Last Updated

March 31, 2026

Status Verified

March 1, 2026

Enrollment Period

6.9 years

First QC Date

March 21, 2022

Last Update Submit

March 30, 2026

Conditions

Friedreich AtaxiaCardiomyopathiesCardiac HypertrophyMyocardial Fibrosis

Keywords

AtaxiaFriedreich's ataxiaPediatricGene therapy

Outcome Measures

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.

    5 Years

Other Outcomes (4)

  • Change in cardiopulmonary exercise testing

    5 Years

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

    5 Years

  • Change in cardiac-relevant parameters in echocardiograms

    5 Years

  • +1 more other outcomes

Study Arms (4)

First Dose Cohort

EXPERIMENTAL

AAVrh.10hFXN will be administered intravenously.

Biological: AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXNDrug: Prednisone

Second Dose Cohort

EXPERIMENTAL

AAVrh.10hFXN will be administered intravenously.

Biological: AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXNDrug: Prednisone

Third Dose Cohort

EXPERIMENTAL

AAVrh.10hFXN will be administered intravenously.

Biological: AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXNDrug: Prednisone

Maximum Tolerated Dose Cohort

EXPERIMENTAL

AAVrh.10hFXN will be administered intravenously.

Biological: AAVrh.10hFXN, serotype rh.10 adeno-associated virus (AAV) gene transfer vector expressing the cDNA coding for human FXNDrug: Prednisone

Interventions

PrednisoneDRUG

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

First Dose CohortMaximum Tolerated Dose CohortSecond Dose CohortThird Dose Cohort
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.

First Dose CohortMaximum Tolerated Dose CohortSecond Dose CohortThird Dose Cohort

Eligibility Criteria

Age12 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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, must meet the following criteria: must be abnormal in ≥2 of the following parameters, at least one of which is an abnormal cardiac MRI left ventricular mass index or abnormal cardiopulmonary exercise test
  • 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 or 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
  • Cardiopulmonary arm crank testing with assessment of VO2 max ≤20 mL/kg-min, peak VO2 ≥10 mL/kg-min while maintaining revolutions of ≥40/min. To insure consistency of effort, peak RER ≥1.0
  • Cardiac MRI stroke volume index \<45 mL/m2
  • Cardiac MRI global longitudinal left ventricular strain \<20%
  • Serum high-sensitivity cardiac troponin above the normal range
  • 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
  • +10 more criteria

You may not qualify if:

  • 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
  • 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
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10021, United States

RECRUITING

Related Publications (1)

  • 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.

    PMID: 37171121DERIVED

MeSH Terms

Conditions

Friedreich AtaxiaCardiomyopathiesCardiomegalyAtaxia

Interventions

Prednisone

Condition Hierarchy (Ancestors)

Spinocerebellar DegenerationsCerebellar DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesSpinal Cord DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMitochondrial DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesHeart DiseasesCardiovascular DiseasesHypertrophyPathological Conditions, AnatomicalPathological Conditions, Signs and SymptomsDyskinesiasNeurologic ManifestationsSigns and Symptoms

Intervention Hierarchy (Ancestors)

PregnadienediolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Ronald G Crystal, MD

    Weill Medical College of Cornell University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Maddie Galbraith, BS

CONTACT

646-962-2672meg4013@med.cornell.edu

Niamh Savage, BS

CONTACT

646-962-5527nis2049@med.cornell.edu

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 21, 2022

First Posted

March 31, 2022

Study Start

February 22, 2022

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2029

Last Updated

March 31, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share

Locations

US(1)