4D-310 in Adults With Fabry Disease and Cardiac Involvement

Phase 1

Recruiting

• 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

Study Timeline

• Study Start: 2022-10-16
• Study First Submitted: 2022-11-04
• Study First Submitted QC: 2022-11-17
• Study First Posted: 2022-11-29
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-19
• Last Update Posted: 2025-02-21
• Primary Completion: 2026-06
• Study Completion: 2030-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Male or female ≥ 18 to ≤65 years of age
2. Pathogenic GLA mutation consistent with Fabry Disease
3. Confirmed diagnosis of classic or late-onset Fabry disease with cardiac involvement
4. Intolerant of ERT, unable or unwilling to receive ERT, or progressive disease despite ERT or migalastat
5. Individuals receiving ERT, must be on a stable dose for at least 6 months
6. Agree to use highly effective contraception

Exclusion Criteria

1. Presence of pre-existing antibodies to 4D-310 capsid or to AGA
2. eGFR <65 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

Note: Other inclusion and exclusion criteria apply

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
4D-310 Dose Level -1	4D-310	Single IV administration of 4D-310 Dose Level -1
4D-310 Dose Level 2	4D-310	Single IV administration of 4D-310 Dose Level 2
4D-310 Dose Level 3	4D-310	Single IV administration of 4D-310 at Dose Level 3
4D-310 Dose Level 1 (No longer enrolling)	4D-310	No longer enrolling - Single IV administration of 4D-310 at Dose Level 1

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-310intravenous (IV) dose

Trial Locations

Locations (4)

Royal Melbourne Hospital; 🇦🇺 Melbourne, Australia

Royal Perth Hospital; 🇦🇺 Perth, Australia

Westmead Hospital; 🇦🇺 Westmead, Australia

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan