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Trial record 2 of 18 for:    sangamo

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

This study is currently recruiting participants.
Verified September 2017 by Sangamo Therapeutics
Sponsor:
ClinicalTrials.gov Identifier:
NCT02702115
First Posted: March 8, 2016
Last Update Posted: September 26, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Sangamo Therapeutics
  Purpose
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.

Condition Intervention Phase
MPS I Biological: SB-318 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Sangamo Therapeutics:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 9
Actual Study Start Date: May 24, 2017
Estimated Study Completion Date: January 2022
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
SB-318: Low Dose
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 2
SB-318: Medium Dose
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 3
SB-318: High Dose
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.

Detailed Description:
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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02702115


Contacts
Contact: Medical Monitor 510-307-7266 clinicaltrials@sangamo.com

Locations
United States, California
UCSF Benioff Children's Hospital Oakland Recruiting
Oakland, California, United States, 94609
Contact: Jill Nicholas    510-428-3885 ext 5241    JiNicholas@mail.cho.org   
Principal Investigator: Paul Harmatz, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Brenda Diethelm-Okita    612-625-1594    dieth001@umn.edu   
Principal Investigator: Chester B Whitley, PhD, MD         
United States, New York
NYU School of Medicine Recruiting
New York, New York, United States, 10016
Contact: Zahra Bakhtiar    212-263-6628    Zahra.Bakhtiar@nyumc.org   
Principal Investigator: Heather A Lau, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Laurie Bailey    513-636-4507    Laurie.Bailey@cchmc.org   
Principal Investigator: Nancy Leslie, M.D.         
Sponsors and Collaborators
Sangamo Therapeutics
Investigators
Study Director: Medical Monitor Sangamo Therapeutics
  More Information

Responsible Party: Sangamo Therapeutics
ClinicalTrials.gov Identifier: NCT02702115     History of Changes
Other Study ID Numbers: SB-318-1502
First Submitted: February 29, 2016
First Posted: March 8, 2016
Last Update Posted: September 26, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sangamo Therapeutics:
gene specific targeted insertion