Objective:

To evalute the safety, tolerability, clinical benefit and protein pathology status following risvodetinib (IkT-148009) treatment in participants with untreated Parkinson’s disease.

Background: RIsvodetinib is an oral, selective potent inhibitor of the non-receptor Ableson Tyrosine Kinases, aka a c-Abl inhibitor.  It has been evaluated in long-term dosing studies of progressive, alpha-synuclien-dependent animal studies of Parkinson’s-like disease.  Once daily therapeutic treatment blocked neural degeneration, rescued lost function and cleared alpha-synuclein pathology.  Risvodetinib also suppressed neuroinflammation in the CNS by a unique mechanism of action.  These studies advanced risvodetinib into multiple clinical trials.

Method:

Risvodetinib is given once daily at 50, 100 or 200 mg or with placebo to 120 participants with untreated Parkinson’s disease.  Participants will be randomized 1:1:1:1 across the three doses or placebo for 12 weeks and then roll into a planned 12 month extension study with the placebo group moving onto the top therapeutic dose. Safety and tolerability will be measured by evaluation of frequency and severity of treatment-emergent adverse events, measures of cardiovascular safety, standard laboratory analyses and monitoring for changes in vision. A hierarchy of 15 secondary endpoints will evaluate the potential benefit of risvodetinib on measures of motor and non-motor function in the Central and Enteric Nervous Systems. Biomarker analysis using CSF/plasma assessments by seed-amplification assay and skin biopsy complement functional assessments.

Results:

As of this writing, the trial is ongoing with 65 participants randomized, 21 potential participants in medical screening and 56 potential participants being evaluated to initiate medical screening.   As of this writing, 15 mild and 2 moderate adverse events have been reported that could possibly have a relationship to treatment.  By the time this presentation will be made public, it is anticipated that the trial will be fully enrolled and blinded or unblinded data evaluating treatment benefit, safety/tolerability of risvodetinib (IkT-148009) over 12 weeks of once daily dosing and protein pathology status will be presented.

Conclusion: Data from a 12 week double-blinded, placebo controlled trial will be presented providing a first look into whether a treatment validated in models of heritable and sporadic PD can impact disease in human Parkinson’s.

References: Werner and Olanow, Mov. DIsorders 37, 6-15 (2022)
Karuppagounder, et al., (2023), DOI: 10.1126/scitranslmed.abp9352
Werner et al., (2024) J. Parkinson’s Dis DOI: 10.3233/JPD-230319

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-201-trial-in-untreated-parkinsons-disease/