Gene Therapy for Fabry Disease

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

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

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 the gene therapy treatment 4D-310 safe for humans?

Preclinical studies of a similar gene therapy, FLT190, in animals showed no related toxicities or adverse events, suggesting it may be safe. Additionally, another gene therapy, ST-920, demonstrated a good safety profile in animal studies. ^{1 2 3 4 5}

How does the treatment 4D-310 for Fabry disease differ from other treatments?

4D-310 is a gene therapy approach for Fabry disease, which uses a viral vector to deliver a functional copy of the GLA gene to the patient's cells, potentially providing a long-lasting solution by enabling the body to produce its own enzyme. This differs from the current standard enzyme replacement therapy, which requires regular infusions of the enzyme. ^{3 5 6 7 8}

What data supports the effectiveness of the treatment 4D-310 for Fabry Disease?

Research on similar gene therapy approaches, like the AAV2/6 vector in mice, shows increased enzyme activity and reduced harmful substances in the body, suggesting potential effectiveness for treatments like 4D-310 in Fabry Disease. ^{2 3 5 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. United States pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS-LSD cohort study. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Gene therapy for fabry disease: a review of the literature. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

AAV2/6 Gene Therapy in a Murine Model of Fabry Disease Results in Supraphysiological Enzyme Activity and Effective Substrate Reduction. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of pegunigalsidase alfa: A multicenter 6-year study in adult patients with Fabry disease. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Multicomponent nanoparticles as nonviral vectors for the treatment of Fabry disease by gene therapy. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34+ Cells for Correction of Fabry Disease. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Therapeutic strategy for Fabry disease by intravenous administration of adeno-associated virus 2 or 9 in α-galactosidase A-deficient mice. [2023]