An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease

This is a prospective multicenter, open-label, dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of 4D-310 following a single IV administration. The study population is comprised of adult males and females with Fabry Disease.

Inclusion criteria

• Male or female ≥ 18 years of age
• Pathogenic GLA mutation consistent with Fabry Disease
• Confirmed diagnosis of classic or late-onset Fabry disease
• Individuals on ERT must be on a stable dose for at least 6 months (and a minimum of 12 months total exposure) prior to study enrollment
• Agree to use highly effective contraception

Exclusion criteria

• Presence of high titer neutralizing antibody to 4D-310 capsid, or presence of high antibody titer to AGA
• eGFR <45 mL/min/1.73 m2
• Undergone kidney transplantation or currently on hemodialysis or peritoneal dialysis
• HIV, active or chronic hepatitis B or C,
• Evidence of liver disease, severe pulmonary disease or diabetes with poor glycemic control
• History of stroke or transient ischemic attack within the last 12 months, or other significant thromboembolic disease history (e.g. pulmonary embolism)
• Contraindication to systemic corticosteroid therapy or immunosuppressive therapy
• Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within the last 12 months.
• Moderately severe to severe cardiovascular disease or uncontrolled hypertension
• Left ventricular ejection fraction of <45% on echocardiogram (ECHO)
• Currently receiving investigational drug, device or therapy or having ever received gene therapy
• History of infusion related response to ERT or any adverse reaction leading to ERT discontinuation
• History of cancer within 2 years (exceptions include non-melanoma skin cancer, localized prostate cancer treated with curative intent)
• Pregnant or breast-feeding