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NCT03041324

Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II

Terminated Phase 1, PHASE2 Results posted Last updated 25 October 2022
What this trial tests

Phase 1, PHASE2 trial testing SB-913 in Mucopolysaccharidosis II in 9 participants. Terminated before completion.

Timeline
11 May 2017
Primary endpoint
7 May 2021
7 May 2021

Quick facts

Lead sponsorSangamo Therapeutics
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment9
Start date11 May 2017
Primary completion7 May 2021
Estimated completion7 May 2021
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Sangamo Therapeutics — full company profile →

Who can join

Adults 5 to 65, any sex, with Mucopolysaccharidosis II or MPS II. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg2
Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg2
Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg5
Effect of SB-913 on IDS Activity Secondary · Baseline and Month 33 after the SB-913 infusion

Change from baseline in clinical laboratory measurement of IDS activity measured in blood, at Month 33.

GroupValue95% CI
Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg-2.6600± 3.5213
Effect of SB-913 on Urine Glycosaminoglycans (GAG) Levels Secondary · Baseline and 36 months after the SB-913 infusion

Change from baseline in total GAG, Dermatan Sulfate GAG, and Heparan Sulfate GAG measured in urine at Month 36

Total GAG
GroupValue95% CI
Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg1.035± 0.03536
Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg-2.6± NA
Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg1.734± 1.58357
Dermatan Sulfate Urine
GroupValue95% CI
Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg-0.025± 1.18087
Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg-3.39± NA
Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg0.262± 0.6985
Heparan Sulfate Urine
GroupValue95% CI
Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg1.895± 2.39709
Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg-7.6± NA
Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg2.880± 2.91261
Annualized Frequency of Idursulfase (or Equivalent ERT) Administration. Secondary · Up to 36 months after the SB-913 infusion

Change from baseline in annualized frequency of idursulfase (or equivalent ERT)

GroupValue95% CI
Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg-2.8± NA
Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg9.9± 25.5
Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg-0.5± 6.13
AAV2/6 Clearance in Plasma, Saliva, Urine, Stool, and Semen Secondary · Up to 36 months after the SB-913 infusion

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.

GroupValue95% CI
Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg2
Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg2
Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg5

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data was collected from the subject's date of screening until their end of study visit which ranged from 24 to 36 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Experimental: Cohort 1 SB-913 Starting Dose 5.00E+12 vg/kg
Serious: 1/2 (50%)
Deaths: 0/2
Experimental: Cohort 2 SB-913 at Next Ascending Dose 1.00E+13 vg/kg
Serious: 1/2 (50%)
Deaths: 0/2
Experimental: Cohort 3 SB-913 at Next Ascending Dose 5.00E+13 vg/kg
Serious: 3/5 (60%)
Deaths: 0/5

Serious adverse events (10 terms)

ReactionSystemExperimental: Cohort 1 SB-…Experimental: Cohort 2 SB-…Experimental: Cohort 3 SB-…
Atrial FibrillationCardiac disorders
Incarcerated Umbilical HerniaGastrointestinal disorders
Intestinal ObstructionGastrointestinal disorders
PyrexiaGeneral disorders
BronchitisInfections and infestations
InfluenzaInfections and infestations
Spinal StenosisMusculoskeletal and connective tissue disorders
Lacunar StrokeNervous system disorders
Device DislocationProduct Issues
Respiratory FailureRespiratory, thoracic and mediastinal disorders
Other adverse events (155 terms — click to expand)

ReactionSystemExperimental: Cohort 1 SB-…Experimental: Cohort 2 SB-…Experimental: Cohort 3 SB-…
Ear CongestionEar and labyrinth disorders
NauseaGastrointestinal disorders
HepatomegalyHepatobiliary disorders
Upper Respiratory Tract InfectionInfections and infestations
Procedural PainInjury, poisoning and procedural complications
Alanine Aminotransferase IncreasedInvestigations
Aspartate Aminotransferase IncreasedInvestigations
Crystals Urine PresentInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
HypaesthesiaNervous system disorders
Nasal CongestionRespiratory, thoracic and mediastinal disorders
FlushingVascular disorders
HypoaesthesiaNervous system disorders
AnemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
SplenomegalyBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Aortic StenosisVascular disorders
CardiomegalyCardiac disorders
Left Atrial DilatationCardiac disorders
Lumbar Spinal StenosisMusculoskeletal and connective tissue disorders
Mitral Spinal StenosisCardiac disorders
PalpatationsCardiac disorders
TachycardiaCardiac disorders
TachypneaCardiac disorders
VertigoEar and labyrinth disorders
Vision BlurredEye disorders
Visual ImpairmentEye disorders
Abdomen Pain, UpperGastrointestinal disorders
Abdominal DiscomfortGastrointestinal disorders
Abdominal PainGastrointestinal disorders
Abdominal Pain, LowerGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrheaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
FlatulenceGastrointestinal disorders
Food PoisoningGastrointestinal disorders
GastritisGastrointestinal disorders
Gastroesophageal Reflux DiseaseGastrointestinal disorders
Jejunal StenosisGastrointestinal disorders

Most-reported serious reactions: Atrial Fibrillation, Incarcerated Umbilical Hernia, Intestinal Obstruction, Pyrexia, Bronchitis, Influenza, Spinal Stenosis, Lacunar Stroke.

Data from ClinicalTrials.gov NCT03041324 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Viral vector platforms within the gene therapy landscape.
    Bulcha JT, Wang Y, Ma H, Tai PWL, et al · · 2021 · cited 899× · PMID 33558455 · DOI 10.1038/s41392-021-00487-6
  2. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects.
    Li H, Yang Y, Hong W, Huang M, et al · · 2020 · cited 733× · PMID 32296011 · DOI 10.1038/s41392-019-0089-y
  3. High levels of AAV vector integration into CRISPR-induced DNA breaks.
    Hanlon KS, Kleinstiver BP, Garcia SP, Zaborowski MP, et al · · 2019 · cited 328× · PMID 31570731 · DOI 10.1038/s41467-019-12449-2
  4. Engineering the next generation of cell-based therapeutics.
    Bashor CJ, Hilton IB, Bandukwala H, Smith DM, et al · · 2022 · cited 271× · PMID 35637318 · DOI 10.1038/s41573-022-00476-6
  5. Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality.
    Hudry E, Vandenberghe LH. · · 2019 · cited 263× · PMID 30844402 · DOI 10.1016/j.neuron.2019.02.017
  6. Enabling Technologies for Personalized and Precision Medicine.
    Ho D, Quake SR, McCabe ERB, Chng WJ, et al · · 2020 · cited 241× · PMID 31980301 · DOI 10.1016/j.tibtech.2019.12.021
  7. CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy.
    Xu Y, Li Z. · · 2020 · cited 202× · PMID 33005303 · DOI 10.1016/j.csbj.2020.08.031
  8. The rapidly evolving view of lysosomal storage diseases.
    Parenti G, Medina DL, Ballabio A. · · 2021 · cited 168× · PMID 33459519 · DOI 10.15252/emmm.202012836

Verify or expand the search:

Other trials of SB-913

Trials testing the same drug.

Other recruiting trials for Mucopolysaccharidosis II

Currently open trials in the same condition.

Other Sangamo Therapeutics trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing