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

Fabry Disease Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04046224
• Other study ID #: ST-920-201
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: July 23, 2019
• Est. completion date: September 2025

Study information

• Verified date: May 2024
• Source: Sangamo Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is the first in human treatment with ST-920, a recombinant AAV2/6 vector encoding the 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 34
• Est. completion date: September 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 COVID-19 at least one month prior to dosing

Additional Inclusion Criteria:

Renal Cohort:

• Screening 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 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, HIV or 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 AFP

• Recent or recurrent hypersensitivity response to 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

• NYHA Class IV

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Biological:
• ST-920
Single dose of investigational product ST-920

Locations

Country	Name	City	State
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Canada	M.A.G.I.C. Clinic Ltd.	Calgary	Alberta
Germany	University Medical Center Hamburg-Eppendorf	Hamburg
Germany	University Hospital of Würzburg	Würzburg
Italy	Azienda Ospedaliero-Universitaria Careggi	Florence	Tuscany
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Royal Free Hospital	London
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Lysosomal and Rare Disorders Research and Treatment Center (LDRTC)	Fairfax	Virginia
United States	University of Iowa Hospital and Clinics	Iowa City	Iowa
United States	University of California, Irvine	Irvine	California
United States	University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Mt. Sinai School of Medicine	New York	New York
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sangamo Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Italy,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) 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