An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- 4D Molecular Therapeutics
- Enrollment
- 18
- Locations
- 4
- Primary Endpoint
- Incidence and severity of adverse events
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
4D-310 Dose Expansion
Dose expansion cohort of single IV administration of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients
Intervention: 4D-310 (Biological)
4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B
Single IV administration of 4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients
Intervention: 4D-310 (Biological)
4D-310 Dose Level 1 - AAV NAb Titer Group B
Single IV administration of 4D-310 Dose Level 1 - AAV NAb titer Group B patients
Intervention: 4D-310 (Biological)
4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A
Single IV administration of 4D-310 Dose Level 1 - AAV NAb Titer Group A patients
Intervention: 4D-310 (Biological)
Outcomes
Primary Outcomes
Incidence and severity of adverse events
Time Frame: 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 Outcomes
- Change from baseline serum globotriaosylsphingosine (lysoGb3)(1 year)
- Change from baseline in serum AGA activity(1 year)