There are two parts to this phase 1/2 study. The first is an open-label phase where three escalating dose levels will be tested. The second phase will take the optimal dose from part one into a randomized, double-blind phase in which patients will receive either active AXO-Lenti-PD or an imitation surgical procedure (ISP).
Primary outcomes are all related to safety at the three-month time point, as measured by: a. incidence of treatment emergent adverse events and serious adverse events; b. changes in clinical laboratory analysis; c. changes in vital signs; d. changes in brain MRI findings; e. changes in physical examination. Secondary outcomes are all related to efficacy, as measured at the six-month timepoint by changes in: a. the Unified Parkinson’s Disease Rating Scale (UPDRS) scores compared to baseline in defined “OFF” and “ON” medication states; b. motor fluctuations compared to baseline as assessed by patient diaries; c. the dyskinesia rating scale from baseline.
Axovant are recruiting patients at a relatively advanced stage of Parkinson’s, with at least five years since diagnosis and a Hoehn and Yahr stage of 3 or 4 in the OFF state. The patients must also be experiencing motor complications. Results from the first cohort using the lowest dose of AXO-Lenti-PD in two patients, were announced in March 2019 , showing efficacy greater than the highest dose of ProSavin® used in previous studies. No serious adverse events were reported. Clearly, caution must be applied given the number of patients and further results are awaited.