Mucopolysaccharidosis IIPhase 1/2NCT03041324
Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II
A Phase 1/2 study testing SB-913 in people with Mucopolysaccharidosis II and MPS II, run by Sangamo Therapeutics at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 65 years
- Conditions the study is for
- Mucopolysaccharidosis II, MPS II
- What is being tested?
- SB-913
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 5 sitesUnited States
- Study dates
- 11 May 2017to 7 May 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 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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 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
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
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of North Carolina
Chapel Hill, North Carolina, 27514
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
NYU School of Medicine, Neurogenetics Division
New York, New York, 10016
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-913, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis II (MPS II)
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.
Read the 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.
- Conditions
- Mucopolysaccharidosis II, MPS II
- Being tested
- SB-913
- Keywords
- MPS ll, Mucopolysaccharidosis II, Hunter syndrome, Gene Editing, Gene therapy, Zinc Finger, ZFN, SB-913, Rare, Genetic, DNA, Sangamo, Genome editing, Champions, Hunter, Gene Specific Targeted Insertion
- Medical subject headings
- Mucopolysaccharidosis II, Sudden Infant Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB-913Biological
Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: SB-913 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Up to 36 months after the SB-913 infusion
Secondary outcomes (4)
Effect of SB-913 on IDS Activity
Change from baseline in clinical laboratory measurement of IDS activity measured in blood, at Month 33.
Measured: Baseline and Month 33 after the SB-913 infusion
Effect of SB-913 on Urine Glycosaminoglycans (GAG) Levels
Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 36
Measured: Baseline and 36 months after the SB-913 infusion
Annualized Frequency of Idursulfase (or Equivalent ERT) Administration.
Change from baseline in annualized frequency of idursulfase (or equivalent ERT)
Measured: Up to 36 months after the SB-913 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.
All the subjects had AAV2/6 clearance in all the samples assessed (i.e., plasma, saliva, urine, stool, and semen) by week 24.
Subjects were only tested until Week 24 because, by that time, they all had 3 consecutive negative tests in all body fluids.
Measured: Up to 36 months after the SB-913 infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2017 (estimated)
- Study start11 May 2017
- Primary completion7 May 2021
- Study completion7 May 2021
Why it stopped: All nine 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 (1)Papers the sponsor has linked to this study.
- Other trials for Mucopolysaccharidosis IIStudies 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
- 9 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
- NCT03041324
- Sponsor's protocol ID
- SB-913-1602
- Status last verified
- Oct 2022
- First submitted
- 13 Jan 2017
- Last updated
- 25 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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 36299240
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. 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-913, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis II (MPS II)
- ClinicalTrials.gov ID
- NCT03041324
- Acronym / sponsor ID
- SB-913-1602
- Conditions
- Mucopolysaccharidosis II, MPS II
- Keywords
- MPS ll, Mucopolysaccharidosis II, Hunter syndrome, Gene Editing, Gene therapy, Zinc Finger, ZFN, SB-913
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: All nine subjects dosed in the study have rolled over to the Long-Term Follow-up Study IVPRP-LT01 \[NCT04628871\]
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Sangamo TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 11 May 2017 (actual)
- Primary completion
- 7 May 2021 (actual)
- Study completion
- 7 May 2021 (actual)
- First posted
- 2 Feb 2017 (estimated)
- Results
- Posted 27 Sep 2022
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 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.
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-913 Starting Dose 5.00E+12 vg/kg | Experimental | Biological: SB-913A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion. |
| Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg | Experimental | Biological: SB-913A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion. |
| Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg | Experimental | Biological: SB-913A single dose of each of the three components of SB-913 [zinc finger nucleases (ZFN1, ZFN2, and hIDUA Donor)] administered via intravenous (IV) infusion. |
Who may qualify
- Ages
- 5 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
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 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
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-913Single dose of each of the 3 components of SB-913: ZFN1, ZFN2 and hIDS Donor | Biological | Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg, Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg, Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg |
Primary outcome
Number of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 Months After the SB-913 Infusion
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)
4 secondary outcomes
Effect of SB-913 on IDS Activity
Time frame: Baseline and Month 33 after the SB-913 infusion
Effect of SB-913 on Urine Glycosaminoglycans (GAG) Levels
Time frame: Baseline and 36 months after the SB-913 infusion
Annualized Frequency of Idursulfase (or Equivalent ERT) Administration.
Time frame: Up to 36 months after the SB-913 infusion
AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen
Time frame: Up to 36 months after the SB-913 infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
- 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.
- Individual participant dataSharing planned: No
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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
5 sites 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-913 in people with Mucopolysaccharidosis II and MPS II, run by Sangamo Therapeutics at 5 sites 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 25 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 27 Sep 2022). 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 Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 36 Months After the SB-913 Infusion (time frame: Up to 36 months after the SB-913 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 NCT03041324, which also lists 1 linked publication.
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 25 Oct 2022.