Clinical trial NCT04046224: Dose-Ranging Study of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy in Subjects With Fabry Disease (STAAR)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Fabry Disease
Keywords: Sangamo
Rare
Lysosomal Storage Disease
Gene Therapy
Lead sponsor: Sangamo Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-08-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 12 months after the ST-920 infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: New York
country: United States
facility: Mt. Sinai School of Medicine
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Fairfax
country: United States
facility: Lysosomal and Rare Disorders Research and Treatment Center (LDRTC)
state: Virginia
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Calgary
country: Canada
facility: M.A.G.I.C. Clinic Ltd.
state: Alberta
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Würzburg
country: Germany
facility: University Hospital of Würzburg
city: Florence
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi
state: Tuscany
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Sangamo Therapeutics, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: