Houari Abdesselem (Qatar)
Hamad Bin Khalifa University Qatar Biomedical Research Institute (QBRI)Author Of 1 Presentation
PHASE 1 FIRST-IN-MAN CLINICAL TRIAL OF INTRAPUTAMENAL CDNF IN PARKINSON’S DISEASE
Abstract
Aims
To assess the safety and tolerability and to explore biological response to intermittent intraputamenal infusions of cerebral dopamine neurotrophic factor (CDNF) in subjects with moderately advanced Parkinson’s disease (PD).
Methods
A randomized, placebo-controlled, double-blind phase 1 trial in 17 patients with moderate PD, comprising placebo or incremental CDNF dosing (once a month) for six months followed by an active treatment six-month extension study. A drug delivery system (Renishaw) was implanted into putamina in all patients. Primary endpoints were safety and tolerability (drug and device). Secondary and exploratory endpoints included UPDRS, dopamine transporter (DAT) PET, actigraphy and CSF biomarkers. Immunoassays and mass spec-based proteomics were used to assess 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. Study drug-related AEs were mild to moderate and primary endpoint for was met. At group level, there were no significant differences in clinical scores (UPDRS, PDQ-39). Increased DAT availability in the putamen was observed at 6 and 12-month timepoints in some patients that received CDNF. Levels of CSF a-synuclein species did not show consistent changes in response to treatment. Three candidate biomarkers were identified in CSF that changed significantly in subjects after receiving CDNF infusions but remained unchanged during the placebo period.
Conclusions
Intraputamenally infused CDNF was 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 individual patients. Candidate biomarkers for monitoring treatment response were identified in the CSF.