VY-AADC02 for Parkinson’s Disease with motor fluctuations

Voyager Therapeutics
Study Design: 
Voyager’s phase 2 study is randomized, placebo-controlled and double-blind, comparing one active dose of VY-AADC02 with a placebo of sham surgery involving a partial burr/twist hole without dura penetration.
Primary outcomes will measure both efficacy and safety. The safety criteria will be evaluated at 12 months and 30 day follow up. The efficacy measures will be taken at 12 months, with enzyme activity also assessed at 45 days. The outcome measures are: a. change in patient rated motor fluctuations; b. percent coverage within the putamen at time of administration of VY-AADC02; c. change in AADC enzyme activity (distribution); d. safety of VY-AADC02 as measured by: i. number of treatment emergent adverse events, ii. changes in vital signs, iii. physical examinations and routine clinical laboratory analysis, (hematology and clinical chemistry), iv. changes in findings on brain images, v. the Columbia-Suicide Severity Rating Scale (C-SSRS), vi. change in impulse control disorders. Secondary outcomes are all related to efficacy, as measured at the twelve-month timepoint by changes in: a. activities of daily living (UPDRS II); b. PD related quality of life (PDQ-39); c. time course response to levodopa (UPDRS III); d. clinical global function (CGI); e. overall non-motor symptoms (NMSS).
Voyager are recruiting patients at least four years since diagnosis, although there is no explicit requirement for the presence of motor complications, despite the study title. The choice of primary and secondary outcome measures has some interesting features. The primary efficacy outcome is a patient rating of motor fluctuations, with UPDRS measures only as secondary outcomes. The assessment of coverage of the putamen on administration and distribution of enzyme activity, both already validated in the phase 1b trial, will give a good indication of target engagement and change in biological activity. The combination of a good safety profile thus far; the change in biological activity leading to significant clinical change; and a favourable regulatory review, give cause for optimism with VY-AADC02.