AAV9- microdystrophin (Solid Biosciences- SGT-001 ) For Duchenne Muscular Dystrophy Treatment: Update on Clinical Studies
AAV9- microdystrophin (Solid Biosciences- SGT-001 )
Clinical Stage and Regulatory Timeline
SGT-001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein.(AAV9.CK.micro-dystrophin). Solid Biosciences is conducting phase 1/2 clinical study (IGNITE) to determine safety of SG-001 dose at 2e14 vg/kg dose.
Viral Vector and Gene Construct
AAV9.CK.micro-dystrophin gene construct consists of muscle specific CK promoter and drives the expression of the minidystrophin gene in the muscle tissue. AAV9 have shown to have high tropism for skeletal and cardiac muscle.
Solid Biosciences is currently conducting a Phase 2 (NCT03368742) nonrandomized clinical study to evaluate safety of the exogenous gene transfer in DMD subjects. The immunofluorescence staining of the muscle biospy showed the successful transfer and expression of microdystrophin in first three patients. The study was on clinical hold from July 2020 to October 2020 as a result of serious adverse event.
Clinical Trial hold and Resolution:
FDA enforced the clinical hold of IGNITE Study from July 2020 to October 2020 as a result of serious adverse event (SAE).Resolution:
Number of Participants in Phase 3 Study- 16
Primary Outcome Measures
- Change from baseline in microdystrophin protein in muscle biopsies (active treatment group)
- Incidence of adverse events
- Incidence of clinical laboratory abnormalities
Key Results from Phase 1/2
A single dose of up to 2e14 vg/kg AAV9.CK.microdystrophin was infused through a peripheral limb vein.
In the high does treatment cohort (n=3, 2e14vg/kg) showed increase in distribution of Dystrophin in muscle biopsy were observed by immunofluorescence staining.
SGT-001 administration results in dose-dependent, muscle wide microdystrophin expression in muscle biopsies collected 90 days post-SGT-001 administration. SGT-001-driven microdystrophin expression resulted in stabilization of dystrophin associated proteins. SGT-001-driven microdystrophin expression resulted in restored enzymatically active neuronal nitric oxide synthase (nNOS) at the sarcolemma.
Not available yet
Serious Adverse Events:
Antibody Response: Not Reported
T cell Response (ELISpot): Not Reported
Solid Biosciences Press Release
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