Category: Parkinson’s Disease: Clinical Trials
Objective: To assess the safety and tolerability and to explore the preliminary efficacy of intermittent intraputamenal monthly infusions of CDNF in subjects with advanced idiopathic Parkinson’s disease (PD).
Background: CDNF is an unconventional neurotrophic factor shown to protect dopaminergic neurons and improve both motor and non-motor functions in rodent and primate models of PD via a unique multi-modal mechanism of action.
Method: A phase I-II clinical trial in 17 patients with idiopathic PD of moderate to advanced severity divided in a placebo-controlled, double-blind six-month study (the main study) followed by an active treatment six-month extension study. The Drug Delivery System (by cosponsor Renishaw) was implanted for intermittent intraputamenal drug delivery to all patients. Patients were randomized to placebo (n=6) or incremental CDNF dosage (n=6 for low-mid dose and n=5 for low-mid-high dose) groups and received doses every four weeks. Primary endpoint was safety and tolerability. Secondary endpoints explored the efficacy of CDNF on PD-related outcomes using validated clinical rating scales and tools including UPDRS. Exploratory endpoints included PET imaging using a DAT tracer, actigraphy and analysis of CSF samples for CDNF levels, α-synuclein and proteomic biomarkers.
Results: At screening, patients with idiopathic PD had on average 10.6±2.6 years disease duration, Hoehn & Yahr 2.4±0.4, off-state UPDRS part III 33.1±7.0, and 5.1±1.4 h daily off-time. Two patients discontinued the main study due to serious adverse events related to infusion procedures with the implanted device. Study drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. Thus, the primary endpoint was met. Initial analysis suggests there were no significant changes between placebo and the two CDNF treatment groups in UPDRS scores between baseline and end of main study. Encouraging signals were observed in DAT PET imaging in the putamen of a few patients that received CDNF but not placebo.
Conclusion: Intraputamenal CDNF infusions were safe and well tolerated. A number of adverse events related to surgical procedures, implanted device or the drug-device combination were recorded, and all have been resolved. The extension study will read out in August 2020.
To cite this abstract in AMA style:
S. Booms, H. Huttunen, J. Koskinen, M. Sjögren, M. Saarma, M. Woolley, B. Murphy, P. Fielder, J. Baker, P. Skinner, J. Rinne, A. Varrone, M. Andreasson, G. Paul-Visse, R. Kivisaari, H. Bjartmarz, G. Lind, P. Almqvist, F. Scheperjans, H. Widner, P. Svenningsson. Phase I-II first-in-human clinical trial of intraputamenal CDNF in Parkinson’s disease: Topline results of the six-month double-blind placebo-controlled main study and the six-month active treatment extension study [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/phase-i-ii-first-in-human-clinical-trial-of-intraputamenal-cdnf-in-parkinsons-disease-topline-results-of-the-six-month-double-blind-placebo-controlled-main-study-and-the-six-month-active-tre/. Accessed May 16, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/phase-i-ii-first-in-human-clinical-trial-of-intraputamenal-cdnf-in-parkinsons-disease-topline-results-of-the-six-month-double-blind-placebo-controlled-main-study-and-the-six-month-active-tre/