Fabry Disease
Conditions
Keywords
Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Cerebral Small Vessel Diseases, Cerebrovascular Disorders, Vascular Diseases, Cardiovascular Diseases, Genetic Diseases, X-Linked, Inborn, Metabolic Diseases, Lipid Metabolism Disorders, Sphingolipidoses, Metabolism, Inborn Errors, Lipidoses, Lipid Metabolism
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICAL4D-310
4D-310 is a novel adeno-associated virus (AAV) gene therapy comprised of two active components: the capsid (4D-C102) and the transgene cassette, which encodes a codon-optimized full length human GLA transgene driven by the CAG promoter. 4D-310 has been engineered so that it cannot replicate (replication incompetent).
Sponsors
4D Molecular Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥ 18 years of age 2. Pathogenic GLA mutation consistent with Fabry Disease 3. Confirmed diagnosis of classic or late-onset Fabry disease 4. 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 5. Agree to use highly effective contraception
Exclusion criteria
1. Presence of high titer neutralizing antibody to 4D-310 capsid, or presence of high antibody titer to AGA 2. eGFR \<45 mL/min/1.73 m2 3. Undergone kidney transplantation or currently on hemodialysis or peritoneal dialysis 4. HIV, active or chronic hepatitis B or C, 5. Evidence of liver disease, severe pulmonary disease or diabetes with poor glycemic control 6. History of stroke or transient ischemic attack within the last 12 months, or other significant thromboembolic disease history (e.g. pulmonary embolism) 7. Contraindication to systemic corticosteroid therapy or immunosuppressive therapy 8. Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within the last 12 months. 9. Moderately severe to severe cardiovascular disease or uncontrolled hypertension 10. Left ventricular ejection fraction of \<45% on echocardiogram (ECHO) 11. Currently receiving investigational drug, device or therapy or having ever received gene therapy 12. History of infusion related response to ERT or any adverse reaction leading to ERT discontinuation 13. History of cancer within 2 years (exceptions include non-melanoma skin cancer, localized prostate cancer treated with curative intent) 14. Pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events | 1 year | Safety and tolerability of 4D-310 following a single IV dose, as assessed by incidence and severity of adverse events, serious adverse events and dose limiting toxicities, including clinically significant changes from baseline to scheduled time points in safety parameters |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in serum AGA activity | 1 year | Change from baseline in serum AGA activity |
| Change from baseline serum globotriaosylsphingosine (lysoGb3) | 1 year | Change from baseline serum globotriaosylsphingosine (lysoGb3) |
Countries
United States
Outcome results
None listed