A phase 1/2 study to evaluate the safety and tolerability of SB-913, a rAAV2/6-based gene therapy in patients with Mucopolysaccharidosis II (MPS II)
- Conditions
- Mucopolysaccharidosis type II (MPS II)MedDRA version: 20.1 Level: PT Classification code 10056889 Term: Mucopolysaccharidosis II System Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2018-000192-33-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
- 32
Inclusion Criteria
Subjects must meet all of the following criteria to be included in the study:
1. Signed informed consent.
2. =5 years of age:
a. Adult cohorts 1 through 4: = 18 years of age;
b. Pediatric cohorts 5 and 6: 12 to 17 years of age; and
c. Pediatric cohorts 7 and 8: 5 to 11 years of age.
3. Clinical diagnosis of MPS II (based on evidence of hepatosplenomegaly, dysostosis multiplex by X-ray, valvular heart disease, or obstructive airway disease); IDS deficiency confirmed by gene sequencing.
4. Sexually mature subjects must agree to use a barrier contraceptive method for prevention of AAV transfer as follows: for female subjects this means that the subjects’ partners must use a condom from dosing with SB-913 and until at least 3 consecutive plasma samples after administration of SB-913 are negative for AAV2/6; for male subjects this means that the subjects must use a condom and must refrain from sperm donation from the time of SB-913 administration until at least 3 consecutive semen samples after administration of SB-913 are negative for AAV2/6. In addition, female participants of child-bearing potential must consent to use a highly effective method of contraception.
5. MRI negative for liver mass as read by a radiologist
Are the trial subjects under 18? yes
Number of subjects for this age range: 7
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from participating in the study
1. Known to be unresponsive to ERT.
2. Neutralizing antibodies in serum (immune response) to AAV2/6.
3. Serious intercurrent illness or clinically significant organic disease (unless secondary to MPS II) such as cardiovascular, hepatic, pulmonary, neurologic, or renal disease.
4. Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B (HBV DNA positive or HBV surface antigen positive) or hepatitis C (HCV RNA viral load) or human immunodeficiency virus (HIV)-1/2 (HIV RNA viral load or HIV antibody positive); to be considered negative for hepatitis C after treatment of an active HCV infection, viral assays in 2 samples collected at least 6 months apart must be negative.
5. Lack of tolerance to idursulfase treatment with significant infusion-associated reactions (IARs) or occurrence of anaphylaxis.
6. Polymorphisms in the ZFN-targeted region of the albumin locus.
7. Liver fibrosis score of 3 or 4 on a 0 to 4 point scale (Desmet et al. 1994) if subject has had a liver biopsy within 2 years of Screening.
8. Markers of hepatic dysfunction as evidenced by one or more of the following:
a) Platelet count <100,000/µL
b) Albumin =3.2 g/dL
c) Total bilirubin >1.5 x upper limit of normal (ULN) and direct bilirubin =0.5 mg/dL
d) Alkaline phosphatase >2.0 x ULN
e) ALT or AST >2.0 x ULN
9. Creatinine = 1.5 mg/dL
10. Weight < 20 kg at Screening visit.
11. Pregnant or breastfeeding female.
12. Contraindication to the use of corticosteroids.
13. Current treatment with systemic (IV or oral) immunomodulatory agent or steroid use (topical treatment allowed, e.g., for asthma or eczema).
14. History of active malignancy in past 5 years (non-melanoma skin cancer or cervical cancer in situ permitted).
15. Participation in prior investigational drug or medical device study within the previous 3 months.
16. Prior treatment with a gene therapy product.
17. History of alcohol or substance abuse that in the opinion of the Principal Investigator may interfere with study compliance.
18. History of therapeutic non-adherence.
19. Elevated or abnormal circulating AFP.
20. Any other reason that, in the opinion of the Principal 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