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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Sangamo Therapeutics
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics
ClinicalTrials.gov Identifier:
NCT03041324
First received: January 13, 2017
Last updated: April 21, 2017
Last verified: April 2017
  Purpose
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 Intervention Phase
Mucopolysaccharidosis II
Biological: SB-913
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: No masking
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)

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-913 as assessed by Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Up to 36 months after the SB-913 infusion ]

Secondary Outcome Measures:
  • Change from baseline over time in urine total GAG [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in urine DS GAG [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in urine HS GAG [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in plasma [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in saliva [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in urine [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in stool [ Time Frame: Up to 36 months after the SB-913 infusion ]
  • Change from baseline over time in AAV2/6 clearance in semen [ Time Frame: Up to 36 months after the SB-913 infusion ]

Estimated Enrollment: 9
Actual Study Start Date: April 21, 2017
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
SB-913: Low Dose
Biological: SB-913
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor
Experimental: Cohort 2
SB-913: Medium Dose
Biological: SB-913
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor
Experimental: Cohort 3
SB-913: High Dose
Biological: SB-913
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor

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.
  Eligibility

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

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03041324

Contacts
Contact: Medical Monitor send email clinicaltrials@sangamo.com

Locations
United States, North Carolina
Chapel Hill, NC Recruiting
Chapel Hill, North Carolina, United States, 27514
Sponsors and Collaborators
Sangamo Therapeutics
Investigators
Study Director: Medical Monitor Sangamo Therapeutics
  More Information

Responsible Party: Sangamo Therapeutics
ClinicalTrials.gov Identifier: NCT03041324     History of Changes
Other Study ID Numbers: SB-913-1602
Study First Received: January 13, 2017
Last Updated: April 21, 2017
Individual Participant Data  
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis II
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
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

ClinicalTrials.gov processed this record on May 25, 2017