Gene Therapy for Fabry Disease

Recruiting at 20 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sangamo Therapeutics

Must not be taking: Immunomodulators, Biologics, Steroids

Disqualifiers: Liver disease, Malignancy, Alcohol abuse, others

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

Compensation: Varies

Number of Visits: 53

Duration: 1 day

33 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on systemic immunomodulatory agents, biologics, or steroids, you may need to stop as their use in the past 6 months is an exclusion criterion. Also, changes to ACE inhibitor or ARB therapy within 4 weeks prior to screening are not allowed.

Is gene therapy for Fabry disease, including ST-920, generally safe in humans?

Research on the gene therapy ST-920 for Fabry disease in mice showed a good safety profile, meaning it did not cause harmful effects in the study. This provides a basis for its development for human use. ^{1 2 3 4 5}

How is the treatment ST-920 for Fabry disease different from other treatments?

ST-920 is a gene therapy that uses an adeno-associated viral vector to deliver a functional copy of the GLA gene, which helps produce the enzyme alpha-galactosidase A. Unlike the current standard enzyme replacement therapy that requires lifelong biweekly infusions, ST-920 aims to provide a more long-lasting solution by enabling the body to produce the enzyme itself, potentially reducing the need for frequent treatments. ^{1 5 6 7 8}

What is the purpose of this trial?

This trial tests ST-920, a treatment using a virus to deliver a gene that helps produce an important enzyme in patients with Fabry disease. The goal is to help these patients by continuously making the enzyme to reduce harmful substances in their bodies. ST-920 is a gene therapy treatment for Fabry disease, which aims to deliver a gene to produce the enzyme alpha-galactosidase A, addressing the enzyme deficiency central to the disease.

Research Team

Medical Monitor

Principal Investigator

Sangamo Therapeutics, Inc.

Eligibility Criteria

Adults with Fabry disease can join this trial. For the cardiac group, they need heart changes like left ventricular hypertrophy or other signs of worsening disease. The renal group requires specific kidney function levels and a history of declining function. All participants must be COVID-19 vaccinated at least one month before treatment.

Inclusion Criteria

My heart shows signs of thickening or disease progression.

I have symptoms like vision changes, pain in hands/feet, less sweating, or skin spots.

I have been diagnosed with Fabry disease.

Exclusion Criteria

You have had problems with alcohol or drugs in the recent past.

You had a bad reaction to ERT in the last 6 months.

My heart condition severely limits my daily activities.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of ST-920

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Regular visits over 52 weeks

Treatment Details

Interventions

• ST-920

Trial Overview The trial is testing ST-920, a gene therapy designed to produce the enzyme α-Gal A in people with Fabry disease. It's given as a single intravenous dose, aiming to reduce or clear harmful substances in the body caused by the disease over a 52-week period.

Participant Groups

Group I: Sequential dose escalation Experimental Treatment 1 Intervention

ST-920 is administered as a single infusion: 1. Cohort 1: 0.5e13 vg/kg 2. Cohort 2: 1.0e13 vg/kg 3. Cohort 3: 3.0e13 vg/kg 4. Cohort 4: 5.0e13 vg/kg

Group II: Expansion Cohorts Experimental Treatment 1 Intervention

1. Anti Alpha-Gal A Antibody Positive Cohort 2. Anti Alpha-Gal A Antibody Negative Cohort 3. Female Cohort 4. Renal Cohort 5. Cardiac Cohort

Who Is Running the Clinical Trial?

Sangamo Therapeutics

Lead Sponsor

Trials

29

Recruited

950+

Findings from Research

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]

References

1. 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]

2. 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]

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

Raised HDL cholesterol in Fabry disease: response to enzyme replacement therapy. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Using CRISPR/Cas9-Mediated GLA Gene Knockout as an In Vitro Drug Screening Model for Fabry Disease. [2021]

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

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

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

Alpha-galactosidase A-Tat fusion enhances storage reduction in hearts and kidneys of Fabry mice. [2021]

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

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

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]