NCT02702115

Brief Summary

The purpose of the study is to evaluate the safety, tolerability of ascending doses of SB-318. SB-318 is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the α-L-iduronidase (IDUA) gene into the Albumin locus in hepatocytes with the goal of lifelong therapeutic production of the IDUA enzyme.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
3

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2017

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

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

February 29, 2016

Completed
8 days until next milestone

First Posted

Study publicly available on registry

March 8, 2016

Completed
1.2 years until next milestone

Study Start

First participant enrolled

May 24, 2017

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 3, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 3, 2021

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

January 26, 2023

Completed
Last Updated

January 26, 2023

Status Verified

December 1, 2022

Enrollment Period

4.4 years

First QC Date

February 29, 2016

Results QC Date

November 3, 2022

Last Update Submit

January 6, 2023

Conditions

MPS I

Keywords

Mucopolysaccharidosis IMPS IHurler-Scheie syndromeGene TherapyGene EditingZinc FingerSB-318RareGeneticDNASangamoGenome editingEmpowersZFNHurlerGene Specific Targeted Insertion

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Treatment-Emergent Adverse Events

    Number of Participants with Treatment-Emergent Adverse Events

    Up to 36 months after the SB-318 infusion

Secondary Outcomes (3)

  • Effect of SB-318 on IDUA Activity

    Baseline and Month 36 after the SB-318 infusion

  • Effect of SB-318 on Urine Glycosaminoglycans (GAG) Levels

    Baseline and 24 months after the SB-318 infusion

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

    Up to 24 months after the SB-318 infusion

Study Arms (3)

Cohort 1: SB-318: Starting Dose 1.00E+13 vg/kg

EXPERIMENTAL

A single dose of each of the three components of SB-318 \[zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)\] administered via intravenous (IV) infusion.

Biological: SB-318

Cohort 2: SB-318 at Next Ascending Dose 5.00E+13 vg/kg

EXPERIMENTAL

A single dose of each of the three components of SB-318 \[zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)\] administered via intravenous (IV) infusion.

Biological: SB-318

Cohort 3: SB-318 at Next Ascending Dose 1.20E+14 vg/kg

EXPERIMENTAL

A single dose of each of the three components of SB-318 \[zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)\] administered via intravenous (IV) infusion.

Biological: SB-318

Interventions

SB-318BIOLOGICAL

A single dose of each of the three components of SB-318 \[zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)\] administered via intravenous (IV) infusion.

Cohort 1: SB-318: Starting Dose 1.00E+13 vg/kgCohort 2: SB-318 at Next Ascending Dose 5.00E+13 vg/kgCohort 3: SB-318 at Next Ascending Dose 1.20E+14 vg/kg

Eligibility Criteria

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

You may qualify if:

  • Male or female ≥ 5 years of age
  • Clinical diagnosis of attenuated MPS I deficiency (Hurler-Scheie, Scheie, or Hurlers status post-HSCT)

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

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Related Publications (2)

  • 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

  • Ou L, Przybilla MJ, Ahlat O, Kim S, Overn P, Jarnes J, O'Sullivan MG, Whitley CB. A Highly Efficacious PS Gene Editing System Corrects Metabolic and Neurological Complications of Mucopolysaccharidosis Type I. Mol Ther. 2020 Jun 3;28(6):1442-1454. doi: 10.1016/j.ymthe.2020.03.018. Epub 2020 Apr 8.

    PMID: 32278382DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis I

Condition Hierarchy (Ancestors)

MucopolysaccharidosesCarbohydrate Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLysosomal Storage DiseasesMucinosesConnective Tissue DiseasesSkin and Connective Tissue DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Limitations and Caveats

Continuous data will be summarized using the following descriptive statistics: the number of subjects (n), mean, standard deviation (SD), median, minimum and maximum, where appropriate. Categorial percentage (%) of subjects for each category, where appropriate.

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

February 29, 2016

First Posted

March 8, 2016

Study Start

May 24, 2017

Primary Completion

November 3, 2021

Study Completion

November 3, 2021

Last Updated

January 26, 2023

Results First Posted

January 26, 2023

Record last verified: 2022-12

Locations

US(1)