- ClinicalTrials.gov ID: NCT05518188
- Recruiting participants (Starts Dec. 19, 2022)
- Not accepting healthy volunteers
- UTSW Principal Investigator: SUSAN THERESA IANNACCONE
summary
AAV9-based AP4M1 gene therapy has promise to treat SPG50 disease, but as with any other new modality, it has some development challenges. Preclinical safety studies in mice, rats, and NHPs demonstrate a favorable safety profile of MELPIDA, at up to twice the proposed human dose of 1E15 vg (doses extrapolated across species by CSF volume, Table 2). Pharmacology studies in the AP4M1 KO mouse model demonstrated a dose-dependent benefit of MELPIDA, with the greatest benefit seen at a dose of 5E11 vg in mice (scaled to approximately 1E15 to 2E15 vg in humans by CSF volume). Importantly, the safety concerns noted in the toxicology studies are balanced against the severe unmet medical need of this patient population and the potential benefit of intrathecal administration of MELPIDA.
objective
Primary outcome: determination of the safety and tolerability of MELPIDA in patients with SPG50, based on development of toxicity Secondary outcome: preliminary exploration of efficacy