4D-310 in Adults With Fabry Disease and Cardiac Involvement
- Conditions
- Fabry Disease
- Interventions
- Biological: 4D-310
- Registration Number
- NCT05629559
- Lead Sponsor
- 4D Molecular Therapeutics
- 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 and cardiac involvement
- 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 and cardiac involvement
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 18
- Adult males and females
- Pathogenic GLA mutation consistent with Fabry Disease
- Confirmed diagnosis of classic or late-onset Fabry disease with cardiac involvement
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A 4D-310 4D-310 Dose Level 1 - AAV NAb Titer Group A patients 4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B 4D-310 4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients 4D-310 Dose Expansion 4D-310 Dose expansion cohort of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients 4D-310 Dose Level 1 - AAV NAb Titer Group B 4D-310 4D-310 Dose Level 1 - AAV NAb titer Group B patients
- Primary Outcome Measures
Name Time Method Incidence and severity of adverse events 1 year Incidence and severity of adverse events following a single IV dose of 4D-310
- Secondary Outcome Measures
Name Time Method 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)
Trial Locations
- Locations (3)
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Royal Perth Hospital
🇦🇺Perth, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Australia