IGNITE-DMD: Phase I/II Ascending Dose Study of Single IV Infusion of SGT-001 Microdystrophin Gene Therapy for DMD-One Year Efficacy and Safety Results

Clinical Trials
61
Barry Byrne MD, PhD, Stephanie Salabarria BHSc, Julie Berthy DNP, Manuela Corti PT, PhD, Carl Morris PhD, Cathryn Clary MD, Joel Schneider PhD, Jeffry Lawrence MD, Sidney Spector MD, PhD, Susan Redican MS, RD, Courtney Shanks MS, Kristy Brown PhD, Patrick Gonzalez PhD
1. University of Florida, 2. University of Florida, 3. University of Florida, 4. University of Florida, 5. Solid Biosciences, 6. Solid Biosciences, 7. Solid Biosciences, 8. Solid Biosciences, 9. Solid Biosciences, 10. Solid Biosciences, 11. Solid Biosciences, 12. Solid Biosciences, 13. Solid Biosciences

IGNITE-DMD is an open-label Phase I/II ascending dose study investigating safety and efficacy of intravenous SGT-001, an AAV9 microdystrophin gene therapy for DMD. SGT-001 is designed to deliver a functional surrogate of the DMD gene, which uniquely includes the nNOS binding domain thought to protect muscle from ischemic damage. Primary outcomes in this study include safety evaluations and measurement of muscle biopsy microdystrophin expression by Western blot, as well as functional outcomes (NSAA; 6MWT). The initial dose Cohort A (5x1013 vg/kg; n=3) was followed by a 4-fold increase in dose administered to Cohort B (2x1014 vg/kg; n=3), after evaluation of microdystrophin expression. All subjects in Cohort B showed microdystrophin expression at Day 90 with an average level of approximately 10% of normal dystrophin. Immunofluorescence analyses demonstrated molecular function through membrane localization of microdystrophin and associated proteins, including β-sarcoglycan and nNOS, with 20-70% of muscle fibers positive for microdystrophin. The most common treatment emergent adverse events were nausea and emesis within 72 hours of dosing. Activation of the terminal pathway (C5b9) of the classical complement system occurred in all subjects resulting in two serious adverse events (SAEs); two other SAEs included an episode of transaminitis and hyperbilirubinemia 4 weeks post dosing which resolved after a transient increase of corticosteroids and one unrelated to SGT-001. Other adverse events included thrombocytopenia, elevation of d-dimer associated with microangiopathy, and acute kidney injury in two subjects. All SAEs are resolved. An update on the progress of the IGNITE-DMD clinical study will be provided, with functional outcomes, including preliminary results of NSAA, 6MWT, and timed function tests highlighted. Additional biomarker and outcomes will also be reported. These preliminary findings support the continued investigation of SGT-001 as a potential therapy for DMD.