Objective: To assess the safety and tolerability of nilotinib (150-300 mg QD) in moderate/advanced and early/de novo Parkinson disease (PD) participants.

Background: Studies in cell and animal models of PD suggest that nilotinib reduces alpha-synuclein pathology. Nilotinib is a c-Abl inhibitor with regulatory approval for certain types of leukemia. A small open-label pilot study tested the safety/tolerability of nilotinib in PD and it was reported that there were positive, though exploratory, signs of efficacy.

Methods: We have initiated a Phase 2a randomized, double-blind, placebo-controlled, parallel group, two cohort study. See Figure 1 for study design. The study will enroll 75 participants with moderate to advanced PD in Cohort 1. The participants will be randomized 1:1:1 to a once daily dose of nilotinib or placebo (150 mg : 300 mg : placebo) for 6 months. Assuming one or more doses are determined to be safe in Cohort 1, Cohort 2 will enroll 60 de novo PD participants randomized 2:1 to a once daily dose of nilotinib or placebo (the highest tolerated and safe dose from cohort 1: placebo) for 12 months. The primary outcome for both cohorts is safety and tolerability. A key secondary objective for Cohort 1 is a futility analysis of the change in the MDS-UPDRS part III score, based on the magnitude of the change observed in the previously completed pilot study (ClinicalTrials.gov NCT02281474). Additional secondary and exploratory outcomes include assessment of symptomatic effect of nilotinib; impact of nilotinib on progression of PD disability (MDS-UPDRS OFF/ON); cognitive function (DRS-2); and quality of life measures. The study also includes a comprehensive battery of serum and spinal fluid biomarkers, measures of serum pharmacokinetics and levels of nilotinib in cerebrospinal fluid. [figure1]

Results: The study is conducted at 25 Parkinson Study Group (PSG) sites in US. The first participant was recruited November 2017. Recruitment for Cohort 1 is expected to be completed in spring 2018, with follow-up continuing through late 2018.

Conclusions: This study will provide further information on safety/tolerability, dose selection and biomarkers profile of Nilotinib as a potential novel therapy to slow PD progression and determine if it is warranted to proceed with the future efficacy studies.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/a-phase-2a-study-of-nilotinib-in-patients-with-advanced-and-early-parkinsons-disease-study-design/