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

Fabry Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04519749
• Other study ID #: 4D-310-C001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 1, 2020
• Est. completion date: June 2030

Study information

• Verified date: April 2024
• Source: 4D Molecular Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: June 2030
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Biological:
• 4D-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).

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Lysosomal & Rare Disorders Research & Treatment Center, Inc	Fairfax	Virginia
United States	University of California at San Diego	La Jolla	California
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
4D Molecular Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events	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	1 year
Secondary	Change from baseline in serum AGA activity	Change from baseline in serum AGA activity	1 year
Secondary	Change from baseline serum globotriaosylsphingosine (lysoGb3)	Change from baseline serum globotriaosylsphingosine (lysoGb3)	1 year