Jim Baker, United Kingdom
Renishaw Neuro Solutions Ltd N/AAuthor Of 1 Presentation
PHASE I-II FIRST-IN-MAN CLINICAL TRIAL OF INTRAPUTAMENAL CDNF IN PARKINSON’S DISEASE: TOPLINE RESULTS OF THE 12-MONTH TREATMENT PERIOD
Abstract
Aims
Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that in preclinical models of Parkinson’s disease (PD) protects dopamine neurons via a unique multi-modal mechanism of action. In this first-in-man study, we assessed the safety and tolerability and explored the efficacy of intermittent bilateral intraputamenal monthly infusions of CDNF protein in subjects with moderately advanced PD.
Methods
A randomized, placebo-controlled, double-blind phase I-II trial in 17 patients with moderate PD, comprising placebo or incremental CDNF dosing for six-month followed by an active treatment six-month extension study. A drug delivery system (Renishaw) was implanted into putamina in all patients. Primary endpoint was safety and tolerability. Secondary and exploratory endpoints included UPDRS, dopamine transporter (DAT) PET, actigraphy and CSF biomarkers.
Results
At screening, the patients had on average disease duration of 10.6±2.6 years, H&Y 2.4±0.4 and >5 h daily off-time. Two patients discontinued in the first 6-month period due to serious adverse events (SAE) related to infusion procedures with the implanted device. Study drug-related AEs were mild to moderate. The primary endpoint was met. At the 12-month timepoint, the least square means change in UPDRS III (off) from baseline in all patients receiving CDNF was -2.2 points (p>0.05, repeated-measures ANCOVA). Increased DAT availability in the putamen was observed at 6 and 12-month timepoints in some patients that received CDNF.
Conclusions
Intraputamenal CDNF infusions were safe and well tolerated despite the AEs and SAEs related to the route of administration. Signs of potential clinical and biological response to the treatment were observed in some patients.