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

Phase 1

Active, not recruiting

• Conditions: Fabry Disease
• Interventions: Biological: 4D-310

• Registration Number: NCT04519749
• 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.

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 Timeline

• Study First Submitted: 2020-08-14
• Study First Submitted QC: 2020-08-17
• Study First Posted: 2020-08-20
• Study Start: 2020-09-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-05
• Last Update Posted: 2024-04-08
• Primary Completion: 2026-01
• Study Completion: 2030-06

Recruitment & Eligibility

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

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
4D-310 Dose Expansion	4D-310	Dose expansion cohort of single IV administration of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients
4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B	4D-310	Single IV administration of 4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients
4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A	4D-310	Single IV administration of 4D-310 Dose Level 1 - AAV NAb Titer Group A patients
4D-310 Dose Level 1 - AAV NAb Titer Group B	4D-310	Single IV administration of 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	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 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 (4)

University of California at San Diego; 🇺🇸 La Jolla, California, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

Lysosomal & Rare Disorders Research & Treatment Center, Inc; 🇺🇸 Fairfax, Virginia, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States