Objective: To report secondary and exploratory analysis of efficacy of nilotinib in moderate/advanced Parkinson’s disease (PD) participants enrolled in NILO-PD study.

Background: Previously completed studies reported significant symptomatic and quality of life effects of nilotinib in participants with moderately advanced PD.

Method: We completed a Phase 2a randomized, double-blind, placebo-controlled, parallel group study (NILO-PD) in moderate to advanced PD. The study enrolled 76 participants randomized 1:1:1 to placebo:150:300 mg nilotinib in matching capsules once daily for 6 months. The primary outcomes were safety and tolerability of nilotinib (results have been previsouly reported). Secondary and exploratory clinical outcomes included change in PD disability (MDS-UPDRS OFF/ON), cognitive function, and quality of life.

Results: The study enrolled 76 participants (39% screen failure) between November 2017 and December 2018 from 25 sites in US. Mean (standard deviation) age was 64.6 years (7.5), disease duration 9.9 years (4.7), MDS-UPDRS OFF score 66.4(19.3) and ON score 48.4(16.2), MOCA score 27.1(2.2). The 300 mg group had transitory worsening of MDS-UPDRS-3 ON at 1 month (p<0.01), which resolved by 6 months. There was no difference in the change of MDS-UPDRS-3 OFF (p=0.17), PDQ-39 (p=0.21), clinician and patient global impression of change from baseline to 6 months between the groups (p=0.61 and p = 0.31, respectively).  In regard to safety and tolerability, there were more premature withdrawals due to adverse events in the nilotinib 300mg group. The most common reasons for dose reduction or temporary suspension were increase in lipase and /or amylase with no imbalance between the groups and no associated clinical symptoms. There was lower incidence of infections in both nilotinib groups compared to placebo (300 vs placebo: p<0.01; 150 vs placebo: p=0.22) but higher incidence of increase in amylase and lipase and nausea.

Conclusion: There was no evidence of any symptomatic effect of nilotinib. This study was not powered or designed to assess disease modifying effect of nilotinib. However, poor CSF penetration of the drug and failure to alter any of monoamine biomarkers, do not warrant further development of nilotinib as a potential disease modifying agent in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/nilo-pd-a-phase-2a-study-of-nilotinib-in-patients-with-moderately-advanced-parkinsons-disease-exploratory-efficacy-outcomes/