We conducted a single-center, phase 2, randomized, double-blind, placebo-controlled study. 43 participants were randomized 1:1 into nilotinib, 200mg, or matching placebo groups. Study drug was taken orally once daily for 6 months followed by one-month wash-out. We hypothesized that nilotinib is safe and can improve cognitive and/or behavioral features in DLB.

Of the forty-three (43) individuals enrolled, fourteen (14) were women (33%), age (mean±SD) was 73±8.5 years. Nilotinib was safe and well-tolerated and more adverse events were noted in the placebo (74) vs nilotinib (37) groups (95% CI, 0.98 to 2.32, p=.054). The number of falls were reduced in the nilotinib (six) compared to placebo (21) group (95% CI, 1.30 to 10.12, p=0.006). ADAS-cognition 14 scores improved by 2.8pts (ADAS-Cog14; 95% CI, 0 to 6.34, p=0.037) in nilotinib versus placebo. Psychiatric features, irritability and cognitive fluctuations were worse in placebo compared to nilotinib. No differences were observed in MDS-UPDRS part II and III, but part I (cognition) improved (0.9 pts, 95% CI, 0 to - 2, p=0.044) in nilotinib compared to placebo. Other cognitive and functional scores, including MoCA (1.5pts, 95% CI, 95% CI, 0 to - 3, p=0.061) and ADCS-ADL, (-3.3 pts, 95% CI, -5 to - 1, p=0.084) trended towards an improvement. CSF HVA as a marker of dopamine level was increased (98.53nM, 5% CI, 27.81 to 169.3, p=0.004). The CSF ratio of pTau181/Aβ42 was reduced (Fig. 3E, -0.13nM, 5% CI, -0.27 to 0.01, p=0.034).

Nilotinib has shown favorable safety and efficacy in patients with LBD supporting a multi-center phase 3 trial for individuals with DLB or advanced Parkinson’s disease with dementia.