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

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ClinicalTrials.gov Identifier: NCT02702115
Recruitment Status : Recruiting
First Posted : March 8, 2016
Last Update Posted : June 7, 2018
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics

February 29, 2016
March 8, 2016
June 7, 2018
May 24, 2017
January 2020   (Final data collection date for primary outcome measure)
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 months after the SB-318 infusion ]
Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in subjects who receive SB-318 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
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 ]
Complete list of historical versions of study NCT02702115 on ClinicalTrials.gov Archive Site
  • Effect of SB-318 on IDUA activity [ Time Frame: Up to 36 months after the SB-318 infusion ]
    Change from baseline clinical laboratory in measurement of IDUA activity measured in plasma and blood leukocytes.
  • Effect of SB-318 on urine glycosaminoglycans (GAG) levels [ Time Frame: Up to 36 months after the SB-318 infusion ]
    Change from baseline in total GAG, DS GAG, and HS GAG (/creatinine ratio) measured in urine.
  • AAV2/6 clearance in plasma, saliva, urine, stool, and semen [ Time Frame: Up to 36 months after the SB-318 infusion ]
    AAV2/6 clearance by measuring vector genomes in plasma, saliva, urine, stool, and semen by PCR.
  • 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 ]
Not Provided
Not Provided
 
Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I
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)
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.
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.
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
MPS I
Biological: SB-318
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.
  • Experimental: Cohort 1: SB-318: Starting Dose
    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.
    Intervention: Biological: SB-318
  • Experimental: Cohort 2: SB-318 at Next Ascending Dose
    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.
    Intervention: Biological: SB-318
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
9
Same as current
January 2022
January 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female >18 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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Medical Monitor 510-307-7266 clinicaltrials@sangamo.com
United States
 
 
NCT02702115
SB-318-1502
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Sangamo Therapeutics
Sangamo Therapeutics
Not Provided
Study Director: Medical Monitor Sangamo Therapeutics
Sangamo Therapeutics
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP