Clinical Trials

Inclusion Criteria:

• Provide a signed informed consent (and assent, if applicable) prior to the initiation of any study-related procedures. Participants under guardianship or partial guardianship will be eligible unless prohibited by local laws or by local/central ethics committees. For participants <18 years old (ie, pediatric participants), written informed consent by parent(s)/legal guardian(s) must be obtained before any study-specific assessments are performed. Consent or assent may also be required for some participants, depending on their age and local requirements.
• Male or female, ages ≥6 years at the time of signing the informed consent (and assent, if applicable).
• Diagnosis of FA, based on clinical phenotype and genotype (GAA expansion on both alleles), with onset of FA occurring at ≤25 years of age.
• Confirmed LVH by any imaging technique (cMRI, ECHO) as per Imaging Manual definition.
• Left ventricular ejection fraction ≥40% as measured by any imaging technique (cMRI, ECHO).
• No documented history of a clinical illness or condition other than FXN variant that is associated with CM or, in the judgment of the investigator, would make the participant inappropriate for study participation.
• Stable medical and/or device therapy consistent with regional guidelines at the investigator’s discretion, without change in medication and dosing for FA and HF in the past 1 month.
• Acceptable hematology laboratory values prior to Day 1:
  • Hemoglobin >9.0 g/dL
  • White blood cells count >4000 cells/μL
  • Platelet count >150,000 platelets/μL
• Acceptable hepatic and renal function laboratory values prior to Day 1:
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.0 × the upper limit of normal (ULN)
  • Total bilirubin <2.0 × ULN (except for Gilbert’s syndrome)
  • Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 (using the simplified modification of diet in renal diseases [sMDRD] formula in adults). In the event sMDRD cannot be determined due to the lack of collection of appropriate data (eg, race), creatinine clearance >30 mL/min (using the ideal body weight Cockroft-Gault formula [Cockcroft and Gault 1976]) may be used. For participants <18 years of age, eGFR will be calculated using the modified Schwartz formula (Appendix 6, Section 12.6).
• Willingness and ability to comply with scheduled visits, laboratory tests, and other study procedures.

Exclusion Criteria:

• Presence of other form(s) of CM contributing to HF (eg, inflammatory or infiltrative CM), clinically significant cardiac anatomic abnormality or congenital cardiac malformation, clinically significant coronary artery disease (eg, coronary revascularization, exercise-induced angina), uncorrected, hemodynamically significant (ie, moderate-severe) primary structural valvular disease not due to CM, per investigator judgment.
• Currently receiving intermittent or continuous intravenous (IV) inotrope infusion, presence of a ventricular assist device, or history of prior heart transplantation. Participants listed for cardiac transplantation may be enrolled, provided transplantation is not likely to occur in the next 12 months.
• Contraindication to cMRI (eg, non-magnetic resonance imaging [MRI]-conditional pacemaker/defibrillator/cardiac resynchronization therapy [CRT]) or MRI contrast (known or suspected) hypersensitivity not amenable to prophylaxis per the investigator’s discretion.
• Nonelective hospitalization within the 30 days prior to enrollment.
• Prior organ transplantation (eg, heart, lung, liver, kidney, or bone marrow). Tissue transplantation that does not require systemic immune suppression (eg, corneal transplantation) is not exclusionary.
• A significant disorder of coagulation and clotting, including, but not limited to, arterial or venous thrombosis or thromboembolism within 90 days prior to enrollment; prothrombin time/international normalized ratio ≥1.2 × ULN; in the absence of anticoagulation; or contraindication to anticoagulation.
• Currently receiving or deemed at high risk of requiring chronic renal replacement therapy (eg, hemodialysis or peritoneal dialysis) within 6 months.
• Initiation of CRT within 6 months prior to screening.
• History of prior gene transfer or cell therapy.
• Participation in a concurrent interventional study.
• Active and/or uncontrolled infection per the discretion of the investigator requiring or which may require systemic treatment within 4 weeks of starting the study, including but not limited to the following:
  • Hepatitis B or C infection (including participants with positive hepatitis B surface antigen, hepatitis B antigen, history of hepatitis B virus [HBV] or hepatitis C virus [HCV] infection, positive HBV core antibody, or any HCV antibody, or detectable HBV or HCV viral load).
  • History of active or latent tuberculosis.
  • Positive human immunodeficiency virus (HIV) serological test at screening, not controlled with antiviral therapy as shown by CD4+ counts ≤200/μL or by a viral load of >200 copies/mL
  • Other viral (excluding herpes simplex virus or human papillomavirus), bacterial, or fungal infection.
• Poorly controlled diabetes (hemoglobin A1c ≥8%) at the investigator's discretion and current guidelines.
• Active hematologic or solid organ malignancy, not including nonmelanoma skin cancer or another carcinoma in situ. Participants with previously resected solid organ malignancies or definitively treated hematologic malignancies may be eligible if there has been no evidence of active malignancy during the prior 5 years.
• Pregnant or nursing.
• Any concomitant medical or psychiatric diagnosis or social status that, at the investigator's discretion, renders the patient unfit for study participation or risk of nonadherence.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 12/20/2024. Questions regarding updates should be directed to the study team contact.