Fabry Disease
Conditions
Keywords
Sangamo, Rare, Lysosomal Storage Disease, Gene Therapy
Brief summary
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.
Interventions
BIOLOGICALST-920
Single dose of investigational product ST-920
Sponsors
Sangamo Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-emergent Adverse Events (TEAEs) - All | Up to 12 months after the ST-920 infusion | All incidences of Treatment-Emergent Adverse Events (TEAEs) in subjects who receive ST-920 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) |
| Incidence of Treatment-emergent Adverse Events (TEAEs) - Related to ST-920 | Up to 12 months post ST-920 infusion | 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) |
| Incidence of Treatment-emergent Adverse Events (TEAEs) - Serious | Up to 12 month post ST-920 infusion | 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) |
| Incidence of Treatment-emergent Adverse Events (TEAEs) - Any TEAEs Leading to Study Discontinuation or Withdrawal | Up to 12 month post ST-920 infusion | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess Alpha Gal-A Activity in Plasma Over Time | up to 12 months post ST-920 infusion | 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. |
Countries
Australia, Canada, Germany, Italy, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Monitor
Sangamo Therapeutics, Inc.
Participant flow
Pre-assignment details
After participants completed screening and were deemed eligible, they moved into a baseline period with additional assessment and testing. Thirty-six participants completed screening but three participants were withdrawn during the baseline period and were never dosed with ST-920. One participant was withdrawn due to not completing baseline assessments while the other two participants were withdrawn but the site investigator due to results received during baseline.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Alpha Gal-A Activity in Plasma | 0.769 nmol/h/mL STANDARD_DEVIATION 1.0875 |
| alpha Gal-A antibodies Negative | 1 Participants |
| alpha Gal-A antibodies Positive | 5 Participants |
| Body Mass Index | 25.71 kg/m^2 STANDARD_DEVIATION 4.338 |
| Enzyme replacement therapy (ERT) status ERT naive | 0 Participants |
| Enzyme replacement therapy (ERT) status ERT pseudo-naive | 6 Participants |
| Enzyme replacement therapy (ERT) status on ERT | 18 Participants |
| Estimated glomerular filtration rate (eGFR) | 109.70 mL/min/1.73m2 STANDARD_DEVIATION 11.738 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 173.3 centimeters STANDARD_DEVIATION 10.28 |
| Migalastat status at screening Migalastat naive | 2 Participants |
| Migalastat status at screening On Migalastat | 1 Participants |
| Migalastat status at screening Previously on Migalastat | 1 Participants |
| Neutralizing antibodies to adeno-associated virus (AAV2/6) Negative | 2 Participants |
| Neutralizing antibodies to adeno-associated virus (AAV2/6) Positive | 0 Participants |
| Plasma Lyso-Gb3 | 75.63 ng/ml STANDARD_DEVIATION 67.162 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment Australia | 5 participants |
| Region of Enrollment Canada | 0 participants |
| Region of Enrollment Germany | 0 participants |
| Region of Enrollment United Kingdom | 0 participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 2 Participants |
| Time (day) from Migalastat last dose to ST-920 infusion | 265.0 Days STANDARD_DEVIATION 284.18 |
| Weight | 73.60 kilograms STANDARD_DEVIATION 13.499 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 3 | 0 / 2 | 0 / 5 | 0 / 5 | 0 / 2 | 0 / 7 | 0 / 5 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 3 / 3 | 2 / 2 | 5 / 5 | 5 / 5 | 2 / 2 | 7 / 7 | 5 / 5 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 1 / 3 | 0 / 2 | 0 / 5 | 0 / 5 | 1 / 2 | 1 / 7 | 1 / 5 |
Outcome results
None listed