A Phase I/II Study to Assess the Safety and Tolerability of ST-920, a rAAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects with Fabry Disease
- Conditions
- Fabry Disease (X-linked lysosomal storage disease)MedDRA version: 20.0 Level: PT Classification code 10016016 Term: Fabry's disease System Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2019-000667-24-GB
- Lead Sponsor
- Sangamo Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 30
Subjects must meet all of the following criteria to be included in the study:
1) Subjects with documented diagnosis of classical Fabry disease as defined by <5% a-Gal A activity in either plasma or leukocytes and one or more of the following symptomatic characteristics of classical Fabry disease: i) cornea verticillata, ii) acroparesthesia, iii) anhidrosis, iv) angiokeratoma.
For subjects who do not have a documented diagnostic a-Gal A activity level, a blood sample should be taken to measure a-Gal A activity levels (in plasma and/or leukocytes).
For those subjects who are on ERT, this blood draw must be taken at least 13 days after their last ERT infusion (trough).
i. If the subject’s level of a-Gal A activity is > 5% and the subject is on ERT, this level of enzyme activity may be due to residual a-Gal A activity from the last ERT infusion. In this case, the diagnosis of classical Fabry disease may be confirmed if the following three criteria are fulfilled:
a. two or more of the following documented symptomatic characteristics of classical Fabry: cornea verticillata, acroparesthesia, anhidrosis, angiokeratoma. If there is documented clustered periumbilicial angiokeratoma, this symptom alone is sufficient as it is a pathognomonic sign of classical Fabry disease;
b. a mutation that is indicative of classical Fabry (i.e. listed in a database, such as http://dbfgp.org); and
c. the a-Gal A activity at trough is below the lower limit of the normal range of the assay.
2. Subjects who are on ERT (14 days [± 3 days] regimen); or are ERT-naïve; or are ERT-pseudo-naïve (defined as not having received ERT treatment in the 6 months prior to consent).
3. For subjects receiving ERT, ERT must have been administered at a stable dose for at least 6 months (defined as not having missed more than 3 doses of ERT during the 6 months prior to consent) and regimen (14 days ± 3 days for at least 3 months prior to enrollment).
4. Male subjects = 18 years of age
5. Sexually mature subjects must agree to use a condom and refrain from sperm donation from the time of ST-920 administration until a minimum of 3 consecutive semen samples are negative for rAAV2/6 after administration of ST-920 and a minimum of 90 days after ST-920 administration
6. Signed, written informed consent of the subject
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Subjects who meet any of the following criteria will be excluded from participating in the study:
1. Known to be unresponsive to ERT in the opinion of the Site Investigator and Medical Monitor (e.g., no documented substrate level decrease on ERT)
2. Current treatment with migalastat (Galafold™) or prior treatment within 3 months of informed consent
3. Positive neutralizing antibody response to AAV6
4. Intercurrent illness expected to impair evaluation of safety or efficacy during the observation period of the study in the opinion of the Site Investigator or Medical Monitor
5. eGFR = 60 ml/min/1.73m^2
6. New York Heart Association Class III or higher
7. Active infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) or an infection with tuberculosis (TB)
8. History of liver disease such as secondary steatosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, cholangitis or biliary disease within 6 months of informed consent; except for Gilbert’s syndrome
9. Abnormal circulating AFP
10. For subjects receiving ERT, recent or continued hypersensitivity response to ERT treatment within 6 months prior to consent, as manifested by significant infusion reaction to ERT in the opinion of the Site Investigator and Medical Monitor
11. One or more of the following: i. Albumin = 3.5 g/dL ii. Total bilirubin > upper limit of normal (ULN) and direct bilirubin = 0.5 mg/dL iii. Alkaline phosphatase (ALP) > 2.0 x ULN iv. Alanine aminotransferase (ALT) > 1.5 x ULN
12. Current or history of systemic (IV or oral) immunomodulatory agent or steroid use in the past 6 months (topical treatment is allowed, e.g. asthma or eczema). Occasional use of systemic steroid may be allowed after discussion with the Medical Monitor.
13. Contraindication to use of corticosteroids for immunosuppression 14. History of malignancy except for non-melanoma skin cancer
15. History of alcohol or substance abuse
16. Participation in prior investigational interventional drug or medical device study within the last 3 months prior to consent (with the exception of implantable loop recorders as in the RaILRoAD trial)
17. Prior treatment with a gene therapy product
18. Known hypersensitivity to components of ST-920 formulation
19. Any other reason that, in the opinion of the Site Investigator or Medical Monitor, would render the subject unsuitable for participation in the study
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method