Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I

January 6, 2023 updated by: Sangamo Therapeutics

A Phase I / 2, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-318, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis I (MPS I)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The objectives of the study are to provide long term expression of IDUA and improve the current clinical outcome of enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT) therapy in subjects with attenuated MPS I, a recessive lysosomal storage disorder that results from mutations in the gene encoding IDUA. SB-318 is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-318 is intended to function by placement of the corrective copy of the IDUA 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 iduronidase for the lifetime of an MPS I patient.

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Oakland, California, United States, 94609
        • UCSF Benioff Children's Hospital Oakland

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

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 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: SB-318: Starting Dose 1.00E+13 vg/kg
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
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.
Experimental: Cohort 2: SB-318 at Next Ascending Dose 5.00E+13 vg/kg
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
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.
Experimental: Cohort 3: SB-318 at Next Ascending Dose 1.20E+14 vg/kg
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
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events
Time Frame: Up to 36 months after the SB-318 infusion
Number of Participants with Treatment-Emergent Adverse Events
Up to 36 months after the SB-318 infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of SB-318 on IDUA Activity
Time Frame: Baseline and Month 36 after the SB-318 infusion
Change from baseline clinical laboratory in measurement of IDUA activity measured in leukocytes.
Baseline and Month 36 after the SB-318 infusion
Effect of SB-318 on Urine Glycosaminoglycans (GAG) Levels
Time Frame: Baseline and 24 months after the SB-318 infusion
Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 24
Baseline and 24 months after the SB-318 infusion
AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen
Time Frame: Up to 24 months after the SB-318 infusion
Subjects with AAV2/6 clearance in plasma, saliva, urine, stool, and semen by PCR by Week 24.
Up to 24 months after the SB-318 infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sangamo Therapeutics

Investigators

  • Study Director: Medical Monitor, Sangamo Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 24, 2017

Primary Completion (Actual)

November 3, 2021

Study Completion (Actual)

November 3, 2021

Study Registration Dates

First Submitted

February 29, 2016

First Submitted That Met QC Criteria

March 2, 2016

First Posted (Estimate)

March 8, 2016

Study Record Updates

Last Update Posted (Estimate)

January 26, 2023

Last Update Submitted That Met QC Criteria

January 6, 2023

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SB-318-1502

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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