Dose-Ranging Study of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy in Subjects With Fabry Disease (STAAR)

A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects With Fabry Disease (STAAR)

This is the first in human treatment with ST-920, an adeno-associated virus (AAV2/6) vector encoding the complementary deoxyribonucleic acid (cDNA) for human a-Gal A. The purpose of this study is to evaluate the safety and tolerability of ascending doses of ST-920. ST-920 aims to provide stable, long-term production of α-Gal A at therapeutic levels in subjects with Fabry disease. The constant production of α-Gal A in humans should, importantly, enable reduction and potentially clearance of Fabry disease substrates Gb3 and lyso-Gb3. On Day 1, patients will be infused intravenously with a single dose of ST-920 and followed for a period of 52 weeks.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Biological: ST-920

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2E 7Z4
      • M.A.G.I.C. Clinic Ltd.
• Germany
  • Hamburg, Germany
    • University Medical Center Hamburg-Eppendorf
  • Würzburg, Germany
    • University hospital of Würzburg
• Italy
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Azienda Ospedaliero-Universitaria Careggi
• Taiwan
  • Taipei, Taiwan
    • National Taiwan University Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • London, United Kingdom
    • Royal Free Hospital
• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
  • Florida
    • Tampa, Florida, United States, 33620
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospital and Clinics
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mt. Sinai School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal and Rare Disorders Research and Treatment Center (LDRTC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years of age
• Documented diagnosis of Fabry disease
• One or more of the following symptoms: i) cornea verticillata, ii) acroparesthesia, iii) anhidrosis, iv) angiokeratoma
• Subject must be fully vaccinated (as per the Centers for Disease Control and Prevention (CDC) definition in the US and as per local guidelines in other countries) for Coronavirus Disease (COVID-19) at least one month prior to dosing

Additional Inclusion Criteria:

Renal Cohort:

• Screening estimated glomerular filtration rate (eGFR) value between 40-90 mL/min/1.73 m²
• Linear negative eGFR slope (estimated from at least 3 serum creatinine values within 18 months, including the value obtained during screening visit) of ≥ 2 mL/min/1.73m²/year

Cardiac Cohort:

• Left ventricular hypertrophy (LVH) in 2D echocardiography or cardiac magnetic resonance imaging (CMR) defined as an end diastolic septum and posterior wall thickness ≥12 mm with no other explanation for LVH, OR presentation with cardiac changes indicative of disease progression such as decreased global longitudinal strain on 2D strain echocardiography or low native T1 mapping on CMR

Exclusion Criteria:

• Neutralizing antibodies to AAV6
• eGFR < 40 ml/min/1.73m2
• New York Heart Association Class III or higher
• Active infection with hepatitis A, B or C, human immunodeficiency virus (HIV) or tuberculosis (TB)
• History of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, biliary disease within 6 months of informed consent; except for Gilbert's syndrome
• Elevated circulating serum alpha fetoprotein (AFP)
• Recent or recurrent hypersensitivity response to enzyme replacement therapy (ERT) within within 6 months prior to consent
• Current or history of systemic (IV or oral) immunomodulatory agents, or biologics or steroid use in the past 6 months prior to consent (topical treatment and inhaled allowed).
• Contraindication to use of corticosteroids
• History of malignancy except for non-melanoma skin cancer and localized prostate cancer treated with curative intent
• Recent history of alcohol or substance abuse
• Participation in investigational interventional drug or medical device study throughout the duration of this study and within previous 3 months prior to consent
• Prior treatment with a gene therapy product
• Known hypersensitivity to components of ST-920 formulation
• Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study including but not limited to risk of COVID-19 infection

Additional exclusion criteria for:

Renal cohort:

• History of renal dialysis or transplantation
• History of acute kidney insufficiency in the 6 months prior to screening
• Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or ARB dose in the 4 weeks prior to screening
• Urine protein to creatinine ratio (UPCR) > 0.5 g/g who are not being treated with an ACE inhibitor or ARB

Cardiac cohort:

• Significant cardiac fibrosis defined by late gadolinium enhancement on CMR
• Any contraindications to CMR as per local hospital/institution guidelines
• Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated within 4 weeks prior to screening or changed ACE inhibitor or ARB dose in the 4 weeks prior to screening
• New York heart association (NYHA) Class IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential dose escalation; ST-920 is administered as a single infusion: Cohort 1: 0.5e13 vg/kg; Cohort 2: 1.0e13 vg/kg; Cohort 3: 3.0e13 vg/kg; Cohort 4: 5.0e13 vg/kg	Biological: ST-920; Single dose of investigational product ST-920
Experimental: Expansion Cohorts; Anti Alpha-Gal A Antibody Positive Cohort; Anti Alpha-Gal A Antibody Negative Cohort; Female Cohort; Renal Cohort; Cardiac Cohort	Biological: ST-920; Single dose of investigational product ST-920

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-emergent Adverse Events (TEAEs) - All	All incidences of Treatment-Emergent Adverse Events (TEAEs) in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)	Up to 12 months after the ST-920 infusion
Incidence of Treatment-emergent Adverse Events (TEAEs) - Related to ST-920	Incidences of Treatment-Emergent Adverse Events (TEAEs) directly related to ST-920 in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)	Up to 12 months post ST-920 infusion
Incidence of Treatment-emergent Adverse Events (TEAEs) - Serious	All incidences of serious Treatment-Emergent Adverse Events (TEAEs) in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)	Up to 12 month post ST-920 infusion
Incidence of Treatment-emergent Adverse Events (TEAEs) - Any TEAEs Leading to Study Discontinuation or Withdrawal	All incidences of Treatment-Emergent Adverse Events (TEAEs) that lead to study discontinuation or withdrawal in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)	Up to 12 month post ST-920 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Assess Alpha Gal-A Activity in Plasma Over Time	Change in alpha Gal-A activity in plasma from baseline at specific time points over the 1-year study period. Two collections occurred during the baseline period and the latter of the two collections was used for the baseline value. The specific time points are Week 24 and Week 52/End of Study (EOS). Plasma α-Gal A activity was measured using a validated fluorometric enzyme activity assay.	up to 12 months post ST-920 infusion

Collaborators and Investigators

• Sponsor: Sangamo Therapeutics
• Investigators: Study Director: Medical Monitor, Sangamo Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): April 10, 2025
• Study Completion (Actual): April 10, 2025

Study Registration Dates

• First Submitted: August 1, 2019
• First Submitted That Met QC Criteria: August 2, 2019
• First Posted (Actual): August 6, 2019

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; Rare; Sangamo; Lysosomal Storage Disease
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Genetic Diseases, X-Linked; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Fabry Disease; Lysosomal Storage Diseases
• Other Study ID Numbers: ST-920-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No