NCT03041324

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
9

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2017

Longer than P75 for phase_1

Geographic Reach
1 country

5 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 13, 2017

Completed
20 days until next milestone

First Posted

Study publicly available on registry

February 2, 2017

Completed
3 months until next milestone

Study Start

First participant enrolled

May 11, 2017

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 7, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 7, 2021

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

September 27, 2022

Completed
Last Updated

October 25, 2022

Status Verified

October 1, 2022

Enrollment Period

4 years

First QC Date

January 13, 2017

Results QC Date

May 7, 2022

Last Update Submit

October 21, 2022

Conditions

Mucopolysaccharidosis IIMPS II

Keywords

MPS llMucopolysaccharidosis IIHunter syndromeGene EditingGene therapyZinc FingerZFNSB-913RareGeneticDNASangamoGenome editingChampionsHunterGene Specific Targeted Insertion

Outcome Measures

Primary Outcomes (1)

  • Number of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 Months After the SB-913 Infusion

    Number of participants with 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)

    Up to 36 months after the SB-913 infusion

Secondary Outcomes (4)

  • Effect of SB-913 on IDS Activity

    Baseline and Month 33 after the SB-913 infusion

  • Effect of SB-913 on Urine Glycosaminoglycans (GAG) Levels

    Baseline and 36 months after the SB-913 infusion

  • Annualized Frequency of Idursulfase (or Equivalent ERT) Administration.

    Up to 36 months after the SB-913 infusion

  • AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen

    Up to 36 months after the SB-913 infusion

Study Arms (3)

Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg

EXPERIMENTAL

A single dose of each of the three components of SB-913 \[zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)\] administered via intravenous (IV) infusion.

Biological: SB-913

Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg

EXPERIMENTAL

A single dose of each of the three components of SB-913 \[zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)\] administered via intravenous (IV) infusion.

Biological: SB-913

Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg

EXPERIMENTAL

A single dose of each of the three components of SB-913 \[zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)\] administered via intravenous (IV) infusion.

Biological: SB-913

Interventions

SB-913BIOLOGICAL

Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor

Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kgCohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kgCohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg

Eligibility Criteria

Age5 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female 5 years to 65 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

NYU School of Medicine, Neurogenetics Division

New York, New York, 10016, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

  • Harmatz P, Prada CE, Burton BK, Lau H, Kessler CM, Cao L, Falaleeva M, Villegas AG, Zeitler J, Meyer K, Miller W, Wong Po Foo C, Vaidya S, Swenson W, Shiue LH, Rouy D, Muenzer J. First-in-human in vivo genome editing via AAV-zinc-finger nucleases for mucopolysaccharidosis I/II and hemophilia B. Mol Ther. 2022 Dec 7;30(12):3587-3600. doi: 10.1016/j.ymthe.2022.10.010. Epub 2022 Oct 25.

    PMID: 36299240DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis IISudden Infant Death

Condition Hierarchy (Ancestors)

X-Linked Intellectual DisabilityIntellectual DisabilityNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesGenetic Diseases, X-LinkedGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHeredodegenerative Disorders, Nervous SystemMucopolysaccharidosesCarbohydrate Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsLysosomal Storage DiseasesMucinosesConnective Tissue DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesDeath, SuddenDeathPathologic ProcessesPathological Conditions, Signs and SymptomsInfant Death

Limitations and Caveats

Due to the limited sample size of 9 subjects, the primary and secondary endpoints could not be analyzed, and this study could not report any conclusions.

Results Point of Contact

Title
Medical Monitor
Organization
Sangamo Therapeutics, Inc.
clinicaltrials@sangamo.com
(510) 307-7266

Study Officials

  • Medical Monitor

    Sangamo Therapeutics

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 13, 2017

First Posted

February 2, 2017

Study Start

May 11, 2017

Primary Completion

May 7, 2021

Study Completion

May 7, 2021

Last Updated

October 25, 2022

Results First Posted

September 27, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

Locations

US(5)