MPS IPhase 1/2NCT02702115
Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I
A Phase 1/2 study testing SB-318 in people with MPS I, run by Sangamo Therapeutics at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- MPS I
- What is being tested?
- SB-318
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 24 May 2017to 3 Nov 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female ≥ 5 years of age
- Clinical diagnosis of attenuated MPS I deficiency (Hurler-Scheie, Scheie, or Hurlers status post-HSCT)
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609
About this study
Official title: 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.
Read the 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.
- Conditions
- MPS I
- Being tested
- SB-318
- Keywords
- Mucopolysaccharidosis I, MPS I, Hurler-Scheie syndrome, Gene Therapy, Gene Editing, Zinc Finger, SB-318, Rare, Genetic, DNA, Sangamo, Genome editing, Empowers, ZFN, Hurler, Gene Specific Targeted Insertion
- Medical subject headings
- Mucopolysaccharidosis I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: SB-318 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events
Number of Participants with Treatment-Emergent Adverse Events
Measured: Up to 36 months after the SB-318 infusion
Secondary outcomes (3)
Effect of SB-318 on IDUA Activity
Change from baseline clinical laboratory in measurement of IDUA activity measured in leukocytes.
Measured: Baseline and Month 36 after the SB-318 infusion
Effect of SB-318 on Urine Glycosaminoglycans (GAG) Levels
Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 24
Measured: Baseline and 24 months after the SB-318 infusion
AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen
Subjects with AAV2/6 clearance in plasma, saliva, urine, stool, and semen by PCR by Week 24.
Measured: Up to 24 months after the SB-318 infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2016 (estimated)
- Study start24 May 2017
- Primary completion3 Nov 2021
- Study completion3 Nov 2021
Why it stopped: All three subjects dosed in the study have rolled over to the Long-Term Follow-up Study IVPRP-LT01 (NCT04628871)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MPS IStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sangamo Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Sangamo Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02702115
- Sponsor's protocol ID
- SB-318-1502
- Status last verified
- Dec 2022
- First submitted
- 29 Feb 2016
- Last updated
- 26 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36299240Ou 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.
PubMed 32278382
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02702115
- Acronym / sponsor ID
- SB-318-1502
- Conditions
- MPS I
- Keywords
- Mucopolysaccharidosis I, MPS I, Hurler-Scheie syndrome, Gene Therapy, Gene Editing, Zinc Finger, SB-318, Rare
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: All three subjects dosed in the study have rolled over to the Long-Term Follow-up Study IVPRP-LT01 (NCT04628871)
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Sangamo TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 24 May 2017 (actual)
- Primary completion
- 3 Nov 2021 (actual)
- Study completion
- 3 Nov 2021 (actual)
- First posted
- 8 Mar 2016 (estimated)
- Results
- Posted 26 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: SB-318: Starting Dose 1.00E+13 vg/kg | Experimental | Biological: SB-318A 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 2: SB-318 at Next Ascending Dose 5.00E+13 vg/kg | Experimental | Biological: SB-318A 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 3: SB-318 at Next Ascending Dose 1.20E+14 vg/kg | Experimental | Biological: SB-318A single dose of each of the three components of SB-318 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Male or female ≥ 5 years of age
- Clinical diagnosis of attenuated MPS I deficiency (Hurler-Scheie, Scheie, or Hurlers status post-HSCT)
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SB-318A 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 | Cohort 1: SB-318: Starting Dose 1.00E+13 vg/kg, Cohort 2: SB-318 at Next Ascending Dose 5.00E+13 vg/kg, Cohort 3: SB-318 at Next Ascending Dose 1.20E+14 vg/kg |
Primary outcome
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
3 secondary outcomes
Effect of SB-318 on IDUA Activity
Time frame: 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
AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen
Time frame: Up to 24 months after the SB-318 infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36299240Harmatz 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.
- Derived from this study: PubMed 32278382Ou 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Sangamo Therapeutics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SB-318 in people with MPS I, run by Sangamo Therapeutics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (time frame: Up to 36 months after the SB-318 infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02702115, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2023.