Gene Therapy for Fabry Disease

Not currently recruiting at 7 trial locations

Overseen By 4DMT 4DMT Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: 4D Molecular Therapeutics

Must be taking: ERT

Must not be taking: Chronic steroids

Disqualifiers: Kidney transplant, HIV, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment, 4D-310, to evaluate its safety and effectiveness for people with Fabry Disease, a genetic disorder that can cause pain, heart problems, and kidney issues. The trial administers a single IV dose of the treatment and includes different groups to test various dose levels. It seeks participants with a confirmed diagnosis of Fabry Disease who have been on stable enzyme replacement therapy (ERT) for at least six months. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on enzyme replacement therapy (ERT), you must be on a stable dose for at least 6 months before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 4D-310 has been tested for safety in people with Fabry disease. In one study, six adults received a single IV infusion of 4D-310, and the results indicated that the treatment was generally well-tolerated. Most side effects were mild, such as headaches and nausea. Importantly, no serious side effects related to the treatment were reported in these patients.

Additionally, early results from another study with three patients showed improvements in heart function and exercise ability after receiving 4D-310. This suggests that the treatment not only seems safe but might also help improve certain health outcomes.

Since this trial is in its early stages, more information is needed to fully understand the safety of 4D-310. However, the current findings are promising and suggest that the treatment is generally safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about 4D-310 for Fabry Disease because it represents a novel approach using gene therapy. Unlike the standard enzyme replacement therapies, which require frequent infusions and only temporarily address the symptoms, 4D-310 aims to provide a long-lasting solution by directly targeting the root cause of the disease—genetic mutations. This treatment utilizes an adeno-associated virus (AAV) vector to deliver a functional copy of the GLA gene, potentially correcting the enzyme deficiency at its source. With its unique single-dose administration, 4D-310 offers the potential for sustained therapeutic effects, reducing the need for ongoing treatment and improving quality of life for patients.

What evidence suggests that this trial's treatments could be effective for Fabry Disease?

Research has shown that 4D-310, a gene therapy, may help treat Fabry disease. In earlier studies, patients who received a single IV dose of 4D-310 experienced improved heart function, increased exercise capacity, and an overall enhancement in quality of life. Specifically, all three patients monitored for a year showed stronger heart pumping. Additionally, a heart tissue sample from one patient confirmed that the gene therapy successfully reached the heart. These early results suggest that 4D-310 might effectively address heart problems in people with Fabry disease. In this trial, participants will receive different dose levels of 4D-310, with some in specific AAV Neutralizing Antibody (NAb) titer groups, to further evaluate its effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Alan H Cohen, MD

Principal Investigator

4D Molecular Therapeutics

Are You a Good Fit for This Trial?

Adults with Fabry Disease can join this trial. They must have a confirmed diagnosis, be on stable enzyme replacement therapy if applicable, and not have severe diseases like liver or lung disease, recent strokes, or uncontrolled diabetes. Participants need to agree to use effective contraception and cannot be pregnant or breastfeeding.

Inclusion Criteria

I have been on the same dose of enzyme replacement therapy for at least 6 months.

Agree to use highly effective contraception

I have been diagnosed with classic or late-onset Fabry disease.

Exclusion Criteria

I do not have HIV or active/chronic hepatitis B or C.

I have severe liver, lung disease, or poorly controlled diabetes.

I haven't had cancer in the past 2 years, except for non-melanoma skin cancer or treated prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Single IV administration of 4D-310 at various dose levels to assess safety, tolerability, and pharmacodynamics

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in serum lysoGb3 and AGA activity

1 year

What Are the Treatments Tested in This Trial?

Interventions

• 4D-310

Trial Overview The trial is testing the safety and effects of a single IV dose of gene therapy called 4D-310 in adults with Fabry Disease. It's an open-label study where everyone knows they're getting the treatment, which will vary in dosage as researchers find the best level.

How Is the Trial Designed?

Group I: 4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B Experimental Treatment 1 Intervention

Single IV administration of 4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients

Group II: 4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A Experimental Treatment 1 Intervention

Single IV administration of 4D-310 Dose Level 1 - AAV NAb Titer Group A patients

Group III: 4D-310 Dose Level 1 - AAV NAb Titer Group B Experimental Treatment 1 Intervention

Single IV administration of 4D-310 Dose Level 1 - AAV NAb titer Group B patients

Group IV: 4D-310 Dose Expansion Experimental Treatment 1 Intervention

Dose expansion cohort of single IV administration of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients

Who Is Running the Clinical Trial?

4D Molecular Therapeutics

Lead Sponsor

Trials

9

Recruited

850+

Published Research Related to This Trial

Enzyme replacement therapy (ERT) for adults with Fabry disease showed a statistically significant decrease in left ventricular mass index (LVMI) and a reduction in the risk of proteinuria, indicating potential benefits in heart health and kidney function over time.

In children with Fabry disease, the study found no significant evidence of effectiveness from ERT, suggesting that the treatment may not have the same benefits for younger patients as it does for adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS-LSD cohort study. Anderson, LJ., Wyatt, KM., Henley, W., et al.[2022]

In a long-term study of 15 adults with Fabry disease, pegunigalsidase alfa, a new enzyme replacement therapy, demonstrated favorable safety with most side effects being mild to moderate, and no severe infusion reactions reported.

Patients showed significant reductions in plasma lyso-Gb3 levels over 60 months, indicating effective treatment, and maintained stable kidney and cardiac function, suggesting long-term benefits of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease. Hughes, D., Gonzalez, D., Maegawa, G., et al.[2023]

Citations

1. ir.4dmoleculartherapeutics.com ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4d-molecular-therapeutics-presents-interim-data-4d-310-inglaxa

Release Details All three patients with 12 months of follow-up demonstrated improvement on cardiac contractility, exercise capacity and quality of life endpoints.

2. 4dmt.gcs-web.com 4dmt.gcs-web.com/news-releases/news-release-details/4dmt-presents-interim-data-4d-310-inglaxa-phase-12-clinical

4DMT Presents Interim Data from 4D-310 INGLAXA Phase 1/2 ... Updated interim safety and efficacy data on six adults with Fabry disease cardiomyopathy treated with a single intravenous (IV) infusion of 4D-310.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05629559

4D-310 in Adults With Fabry Disease and Cardiac ... It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

4. fabrydiseasenews.com fabrydiseasenews.com/4d-310-fabry-disease/

4D-310 for Fabry disease For one patient who underwent a cardiac biopsy, results showed that the gene therapy effectively reached the heart without causing ...

5. firstwordpharma.com firstwordpharma.com/story/5884214

4DMT seeks to right its gene therapy ship after FDA lifts ... 4D Molecular Therapeutics (4DMT) has received a go-ahead from the FDA to resume testing its gene therapy for Fabry disease cardiomyopathy, ...

6. 4dmoleculartherapeutics.com 4dmoleculartherapeutics.com/wp-content/uploads/Thomas_02062025_4D-310Fabry_poster338.pdf

Phase 1/2 Clinical Trial 4D-310 in Adults with Fabry ... ‒ Interim analysis of clinical activity and safety outcomes included all study participants in dose cohort 1 (1×1013 vg/kg) with evaluable data ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04519749

An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in ... This is a prospective multicenter, open-label, dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of 4D-310 following a single IV ...