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

Sponsor

4D Molecular Therapeutics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT05629559

Collaborator

(none)

Enrollment

Locations

Arms

67.5

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Fabry Disease	Biological: 4D-310 Biological: 4D-310 Biological: 4D-310	Phase 1/Phase 2

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label, Phase 1/2a Trial of Gene Therapy 4D-310 in Adults With Fabry Disease and Cardiac Involvement

Actual Study Start Date :

Oct 16, 2022

Anticipated Primary Completion Date :

May 31, 2024

Anticipated Study Completion Date :

May 31, 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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