The 201 Trial: a placebo-controlled randomized phase 2 study of safety and tolerance of the c-Abl kinase inhibitor risvodetinib in untreated Parkinson’s disease
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: The nonreceptor Abelson (Abl) tyrosine kinases have been implicated as key drivers of initiation and progression in Parkinson's disease (PD). Risvodetinib, a potent, brain-penetrant, selective inhibitor of the nonreceptor Abl kinases c-Abl1 and c-Abl2/Arg (collectively, c-Abl), was evaluated in a randomized, double-blind, placebo-controlled phase 2a trial ('the 201 Trial') using once-daily 50 mg, 100 mg, 200 mg or placebo in 137 participants with early, untreated PD. The primary end points in safety and tolerability were met, with 95% of enrolled participants completing the 12-week dosing regimen and a 2-week safety follow-up. Both the average number of adverse events per person and the fraction of participants experiencing at least one treatment-emergent adverse event were similar between risvodetinib and placebo treatment groups, indicating that risvodetinib was safe and well tolerated. Although the trial was not powered to measure efficacy, 14 secondary end points evaluated motor and nonmotor features of disease in hierarchical order. The primary hierarchical secondary end point of the Movement Disorder Society revision to the Unified PD Rating Scale sum of Parts II + III did not reach statistical significance. The study findings indicate that risvodetinib is safe and well tolerated. Longer duration trials are needed to evaluate its potential clinical efficacy. ClinicalTrials.gov registration: NCT05424276 .
Source: Nature Aging
Authors: M. H. Werner, A. McGarry, C. Meyer, E. Mancino, C. Klint, J. Pellecchia, K. Kieburtz, T. Levine, B. Bellaire, C. Gibbons, R. Freeman, A. Ellenbogen, K. Klos, M. Ospina, R. A. Hauser, K. Shannon, H. Asaad, A. Park, P. McAllister, S. H. Isaacson, M. S. LeDoux, R. Dhall, D. Shpiner, P. Charles, P. Agarwal, E. Peckham, P. Mazzeo, M. Davis, R. Pahwa, M. Brodsky, M. Lew, L. Purino, S. Mantri, S. Parashos, W. Justiz, M. Chachar, B. Robottom, E. Budman, K. Blindauer, S. Bellows, J. Goudreau, S. Steen, C. W. Olanow
Institutions: Cooper Medical School of Rowan University, Cooper Norcross Health, Rowan University, Inhibikase Therapeutics (United States), Beth Israel Deaconess Medical Center, Harvard University, Quest Research Institute, University of South Florida, University of Wisconsin–Madison, The Ohio State University, University of Arkansas for Medical Sciences, University of Miami, Vanderbilt University Medical Center, Evergreen Health Medical Center, Central Texas Neurology Consultants, University of Kansas Medical Center, Oregon Health & Science University, University of Southern California, Raleigh Neurology Associates, Medical College of Wisconsin, Baylor College of Medicine, Michigan State University, Icahn School of Medicine at Mount Sinai
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funder: Rush University
OpenAlex ID: W7130655259