Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I
MPS I
About this trial
This is an interventional treatment trial for MPS I focused on measuring Mucopolysaccharidosis I, MPS I, Hurler-Scheie syndrome, Gene Therapy, Gene Editing, Zinc Finger, SB-318, Rare, Genetic, DNA, Sangamo, Genome editing, Empowers, ZFN, Hurler, Gene Specific Targeted Insertion
Eligibility Criteria
Inclusion Criteria:
- Male or female ≥ 5 years of age
- Clinical diagnosis of attenuated MPS I deficiency (Hurler-Scheie, Scheie, or Hurlers status post-HSCT)
Exclusion Criteria:
- Known to be unresponsive to ERT
- Neutralizing antibodies to AAV 2/6
- Serious intercurrent illness or clinically significant organic disease (unless secondary to MPS I)
- Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B or hepatitis C or HIV 1/2
- Lack of tolerance to laronidase treatment with significant IARs or occurrence of anaphylaxis
- Markers of hepatic dysfunction
- Creatinine ≥ 1.5 mg/dL
- Contraindication to the use of corticosteroids for immunosuppression
- Current treatment with systemic (IV or oral) immunomodulatory agent or steroid use (topical treatment allowed)
- Participation in prior investigational drug or medical device study within the previous 3 months
- Prior treatment with a gene therapy product
- Elevated or abnormal circulating α-fetoprotein (AFP)
- Weight <20 kg at Screening Visit
Sites / Locations
- UCSF Benioff Children's Hospital Oakland
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Cohort 1: SB-318: Starting Dose 1.00E+13 vg/kg
Cohort 2: SB-318 at Next Ascending Dose 5.00E+13 vg/kg
Cohort 3: SB-318 at Next Ascending Dose 1.20E+14 vg/kg
A single dose of each of the three components of SB-318 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.
A single dose of each of the three components of SB-318 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.
A single dose of each of the three components of SB-318 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion.