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

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. Identifier: NCT03041324
Recruitment Status : Recruiting
First Posted : February 2, 2017
Last Update Posted : September 3, 2018
Information provided by (Responsible Party):
Sangamo Therapeutics

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.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis II MPS II Biological: SB-913 Phase 1

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Sequential 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-913, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis II (MPS II)
Actual Study Start Date : May 11, 2017
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2022

Arm Intervention/treatment
Experimental: Cohort 1
Single IV infusion of SB-913 at low dose
Biological: SB-913
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor

Experimental: Cohort 2
Single IV infusion of SB-913 at medium dose
Biological: SB-913
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor

Experimental: Cohort 3
Single IV infusion of SB-913 at high dose
Biological: SB-913
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor

Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 months after the SB-913 infusion ]
    Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in subjects who receive SB-913 as assessed by Common Terminology Criteria for Adverse Events (CTCAE)

Secondary Outcome Measures :
  1. Effect of SB-913 on IDS activity [ Time Frame: Up to 36 months after the SB-913 infusion ]
    Change from baseline in clinical laboratory measurement of IDS activity measured in plasma.

  2. Effect of SB-913 on urine glycosaminoglycans (GAG) levels [ Time Frame: Up to 36 months after the SB-913 infusion ]
    Change from baseline in total GAG, DS GAG, and HS GAG (/creatinine ratio) measured in urine.

  3. AAV2/6 clearance in plasma, saliva, urine, stool, and semen [ Time Frame: Up to 36 months after the SB-913 infusion ]
    AAV2/6 clearance by measuring vector genomes in plasma, saliva, urine, stool, and semen by PCR.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male >18 years of age
  • Clinical diagnosis of attenuated MPS II (based on evidence of hepatosplenomegaly, dysostosis multiplex by X-ray, valvular heart disease, or obstructive airway disease)

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 II)
  • Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B or hepatitis C or HIV 1/2
  • Lack of tolerance to idursulfase 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)

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 identifier (NCT number): NCT03041324

Contact: Medical Monitor send email

United States, California
UCSF Benioff Children's Hospital Oakland Recruiting
Oakland, California, United States, 94609
Contact: Jill Nicholas    510-428-3885 ext 5241   
Principal Investigator: Paul Harmatz, MD         
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Rachel Katz    312-227-6764   
Contact: Carolyn Ries    312-227-6004   
Principal Investigator: Barbara Burton, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Patricia Grover    612-672-5151   
Principal Investigator: Chester Whitley, MD, PhD         
United States, New York
NYU School of Medicine, Neurogenetics Division Recruiting
New York, New York, United States, 10016
Contact: Sara Rodriguez    212-263-0139   
Principal Investigator: Heather A. Lau, M.D.         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Heather Preiss, RN    919-842-5731   
Principal Investigator: Joesph Muenzer, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Laurie Bailey    513-636-4507   
Principal Investigator: Carlos E Prada, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Genevieve Nesom    267-426-1368   
Principal Investigator: Can Ficicioglu, MD         
Sponsors and Collaborators
Sangamo Therapeutics
Study Director: Medical Monitor Sangamo Therapeutics

Responsible Party: Sangamo Therapeutics Identifier: NCT03041324     History of Changes
Other Study ID Numbers: SB-913-1602
First Posted: February 2, 2017    Key Record Dates
Last Update Posted: September 3, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Sangamo Therapeutics:
MPS ll
Hunter syndrome
gene editing
gene therapy
zinc finger
Genomic editing

Additional relevant MeSH terms:
Mucopolysaccharidosis II
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System