Clinical Trial: Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-913, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccha

Brief Summary: The purpose of the study is to evaluate the safety, tolerability and effect on leukocyte and plasma Iduronate 2-Sulfatase (IDS) enzyme activity of ascending doses of SB-913. SB-913 is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the IDS gene into the Albumin locus in hepatocytes with the goal of lifelong therapeutic production of the IDS enzyme.

Detailed Summary: The objectives of the study are to provide long term expression of IDS and improve the current clinical outcome of enzyme replacement therapy (ERT) in subjects with MPS II, a recessive lysosomal storage disorder that results from mutations in the gene encoding IDS. SB-913 is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-913 is intended to function by placement of the corrective copy of IDS transgene into the genome of the subject's own hepatocytes, under the control of the highly expressed endogenous albumin locus, and is expected to provide permanent, liver-specific expression of Iduronate 2-Sulfatase for the lifetime of an MPS II patient.
Sponsor: Sangamo Therapeutics

Current Primary Outcome: Treatment related Adverse Events in subjects who received SB-913 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 36 months after the SB-913 infusion ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change from baseline over time in urine total GAG [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in urine DS GAG [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in urine HS GAG [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in plasma [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in saliva [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in urine [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in stool [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in semen [ Time Frame: Up to 36 months after the SB-913 infusion ]


Original Secondary Outcome: Same as current

Information By: Sangamo Therapeutics

Dates:
Date Received: January 13, 2017
Date Started: April 21, 2017
Date Completion: February 2022
Last Updated: April 21, 2017
Last Verified: April 2017