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

a study on MPS I

Summary

for people ages 18 years and up (full criteria)
at Oakland, California and other locations
study started
estimated completion
Paul Harmatz

Description

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.

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 Mucopolysaccharidosis I (MPS I)

Details

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.

Keywords

MPS Igene specific targeted insertionMucopolysaccharidosis IHurler-Scheie syndromeHurlerScheie syndromegene therapygene editingzinc fingerSB-318raregeneticDNASangamoScheieGenome editingEmpowersHurler syndromeMucopolysaccharidosesZinc

Eligibility

You can join if…

Open to people ages 18 years and up

  • Male or female >18 years of age
  • Clinical diagnosis of attenuated MPS I deficiency (Hurler-Scheie, Scheie, or Hurlers status post-HSCT)

You CAN'T join if...

  • 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)

Locations

  • UCSF Benioff Children's Hospital Oakland accepting new patients
    OaklandCalifornia94609United States
  • University of Minnesota accepting new patients
    MinneapolisMinnesota55455United States

Lead Scientist

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Sangamo Therapeutics
ID
NCT02702115
Phase
Phase 1
Study Type
Interventional
Last Updated