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History of Changes for Study: NCT03041324
Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II
Latest version (submitted August 30, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 31, 2017 None (earliest Version on record)
2 February 6, 2017 Arms and Interventions, Study Status and Study Design
3 April 21, 2017 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 July 24, 2017 Contacts/Locations and Study Status
5 July 26, 2017 Study Status
6 September 2, 2017 Study Status and Contacts/Locations
7 September 14, 2017 Contacts/Locations and Study Status
8 October 18, 2017 Study Status and Contacts/Locations
9 December 6, 2017 Study Status and Contacts/Locations
10 February 5, 2018 Outcome Measures, Conditions and Study Status
11 February 27, 2018 Contacts/Locations and Study Status
12 April 12, 2018 Study Status and Arms and Interventions
13 June 5, 2018 Contacts/Locations and Study Status
14 August 30, 2018 Contacts/Locations and Study Status
15 November 20, 2018 Eligibility, Arms and Interventions, Study Status, Contacts/Locations, Outcome Measures and Study Design
16 January 25, 2019 Study Status and Contacts/Locations
17 June 28, 2019 Recruitment Status, Arms and Interventions, Study Status, Contacts/Locations, Study Design, Outcome Measures, Conditions and Study Identification
18 November 4, 2019 Contacts/Locations and Study Status
19 December 4, 2019 Study Status and Contacts/Locations
20 March 1, 2021 Study Status
21 June 3, 2021 Recruitment Status and Study Status
22 May 7, 2022
Quality Control Review has not concluded Returned: June 3, 2022
Outcome Measures, Arms and Interventions, Study Status, Eligibility, Document Section
23 June 17, 2022
Quality Control Review has not concluded Returned: July 12, 2022
Outcome Measures, Document Section, Study Status and Baseline Characteristics
24 August 30, 2022 Study Status, Outcome Measures
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Study NCT03041324
Submitted Date:  January 31, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: SB-913-1602
Brief Title: Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II
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)
Secondary IDs:
Open or close this module Study Status
Record Verification: January 2017
Overall Status: Not yet recruiting
Study Start: April 2017
Primary Completion: February 2021 [Anticipated]
Study Completion: February 2022 [Anticipated]
First Submitted: January 13, 2017
First Submitted that
Met QC Criteria:
January 31, 2017
First Posted: February 2, 2017 [Estimate]
Last Update Submitted that
Met QC Criteria:
January 31, 2017
Last Update Posted: February 2, 2017 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Sangamo Therapeutics
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.
Open or close this module Conditions
Conditions: Mucopolysaccharidosis II
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 9 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Cohort 1
SB-913: Low Dose
Genetic: 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
Genetic: 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
Genetic: SB-913
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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:
1. Change from baseline over time in urine total GAG
[ Time Frame: Up to 36 months after the SB-913 infusion ]

2. Change from baseline over time in urine DS GAG
[ Time Frame: Up to 36 months after the SB-913 infusion ]

3. Change from baseline over time in urine HS GAG
[ Time Frame: Up to 36 months after the SB-913 infusion ]

4. Change from baseline over time in AAV2/6 clearance in plasma
[ Time Frame: Up to 36 months after the SB-913 infusion ]

5. Change from baseline over time in AAV2/6 clearance in saliva
[ Time Frame: Up to 36 months after the SB-913 infusion ]

6. Change from baseline over time in AAV2/6 clearance in urine
[ Time Frame: Up to 36 months after the SB-913 infusion ]

7. Change from baseline over time in AAV2/6 clearance in stool
[ Time Frame: Up to 36 months after the SB-913 infusion ]

8. Change from baseline over time in AAV2/6 clearance in semen
[ Time Frame: Up to 36 months after the SB-913 infusion ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Male
Gender Based:
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)
Open or close this module Contacts/Locations
Central Contact Person: Medical Monitor
Email: clinicaltrials@sangamo.com
Study Officials: Medical Monitor
Study Director
Sangamo Therapeutics
Locations:
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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