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Trial record 22 of 49 for:    Hunter Syndrome

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

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ClinicalTrials.gov Identifier: NCT03041324
Recruitment Status : Recruiting
First Posted : February 2, 2017
Last Update Posted : January 29, 2019
Sponsor:
Information provided by (Responsible Party):
Sangamo Therapeutics

Tracking Information
First Submitted Date  ICMJE January 13, 2017
First Posted Date  ICMJE February 2, 2017
Last Update Posted Date January 29, 2019
Actual Study Start Date  ICMJE May 11, 2017
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 5, 2018)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
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 ]
Change History Complete list of historical versions of study NCT03041324 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2018)
  • 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.
  • 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.
  • Annualized frequency of idursulfase (or equivalent ERT) administration. [ Time Frame: Up to 36 months after the SB-913 infusion ]
    Change from baseline in annualized frequency of idursulfase (or equivalent ERT)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II
Official Title  ICMJE 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)
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Mucopolysaccharidosis II
  • MPS II
Intervention  ICMJE Biological: SB-913
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor
Study Arms  ICMJE
  • Experimental: Low Dose Group
    Single IV infusion of SB-913
    Intervention: Biological: SB-913
  • Experimental: Medium Dose Group
    Single IV infusion of SB-913
    Intervention: Biological: SB-913
  • Experimental: High Dose Group
    Single IV infusion of SB-913
    Intervention: Biological: SB-913
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2018)
23
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2017)
9
Estimated Study Completion Date  ICMJE February 2022
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female ≥ 5 years of age
  • Clinical diagnosis of MPS II (based on evidence of hepatosplenomegaly, dysostosis multiplex by X-ray, valvular heart disease, or obstructive airway disease) IDS deficiency confirmed by gene sequencing.

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)
  • Weight < 20 kg at Screening Visit
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Monitor send email clinicaltrials@sangamo.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03041324
Other Study ID Numbers  ICMJE SB-913-1602
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sangamo Therapeutics
Study Sponsor  ICMJE Sangamo Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Sangamo Therapeutics
PRS Account Sangamo Therapeutics
Verification Date January 2019

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