Clinical Trial: Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I

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-318, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccha

Brief Summary: The purpose of the study is to evaluate the safety, tolerability of ascending doses of SB-318. SB-318 is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the α-L-iduronidase (IDUA) gene into the Albumin locus in hepatocytes with the goal of lifelong therapeutic production of the IDUA enzyme.

Detailed Summary: The objectives of the study are to provide long term expression of IDUA and improve the current clinical outcome of enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT) therapy in subjects with attenuated MPS I, a recessive lysosomal storage disorder that results from mutations in the gene encoding IDUA. SB-318 is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-318 is intended to function by placement of the corrective copy of the IDUA 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 iduronidase for the lifetime of an MPS I patient.
Sponsor: Sangamo Therapeutics

Current Primary Outcome: Treatment related Adverse Events in subjects who received SB-318 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 36 months after the SB-318 infusion ]

Assessment of treatment related Adverse Events in subjects who received SB-318 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)


Original Primary Outcome: Treatment related Adverse Events in subjects who received SB-318 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 36 months after the SB-318 infusion ]

Current Secondary Outcome:

  • Effect of SB-318 on urine glycosaminoglycans (GAG) levels [ Time Frame: Up to 36 months after the SB-318 infusion ]
    Measurement of effect of SB-318 on urine glycosaminoglycans (GAG) levels
  • AAV2/6 clearance in plasma, saliva, urine, stool, and semen [ Time Frame: Up to 36 months after the SB-318 infusion ]
    Measurement of AAV2/6 clearance in plasma, saliva, urine, stool, and semen


Original Secondary Outcome:

  • Effect of SB-318 on leukocyte IDUA activity [ Time Frame: Up to 36 months after the SB-318 infusion ]
  • Effect of SB-318 on plasma IDUA activity [ Time Frame: Up to 36 months after the SB-318 infusion ]
  • Effect of SB-318 on liver biopsy for measurement of IDUA [ Time Frame: Up to 36 months after the SB-318 infusion ]
  • Effect of SB-318 on liver biopsy for measurement of glycosaminoglycans (GAG) [ Time Frame: Up to 36 months after the SB-318 infusion ]


Information By: Sangamo Therapeutics

Dates:
Date Received: February 29, 2016
Date Started: May 2017
Date Completion: January 2022
Last Updated: May 2, 2017
Last Verified: May 2017