The Parkinson Alliance

The Parkinson Alliance is using its 2017 distribution to fund:

Phase IIa Safety and Tolerability Trial of Nilotinib in People with Parkinson’s Disease

PROJECT TITLE:  Phase IIa Safety and Tolerability Trial of Nilotinib in People with Parkinson’s Disease

Investigator/Author:  Tanya Simuni, MD, Chief of Movement Disorders at Northwestern University Feinberg School of Medicine

Objective:  The Phase IIa trial aims to expand on preliminary safety findings and assess potential side effects to better understand the implications of nilotinib’s long-term use in Parkinson’s. The study also will further explore nilotinib’s potential to treat symptoms or to slow or stop disease progression.

Background:  Previous research has shown higher levels of the c-Abl protein are activated in the brains of people with Parkinson’s disease (PD), and studies have linked c-Abl to pathways associated with the disease. Impeding the activity of this protein could potentially slow or stop the progression of PD, making it an emerging therapeutic target. While much work remains to understand the role of this protein in Parkinson’s, it showed early promise as a potential therapeutic target. A small open-label Phase I clinical trial evaluated the safety and tolerability of nilotinib, a c-Abl inhibitor, in people with Parkinson’s and preliminary data showed potential benefit.

Methods/Design:  In The Michael J. Fox Foundation’s multicenter, randomized, double-blind, placebo-controlled Phase IIa trial, 75 people with moderate to advanced PD will be randomized to receive 150 mg of nilotinib, 300 mg of nilotinib or placebo daily for six months. Neither patients nor clinicians will know what therapy each person receives until the end of the trial. After six months, all treatments will be stopped and patients will be monitored for another 10 weeks. Results will be analyzed to determine if the drug is safe and tolerable, and which of the drug doses appears to be the maximum tolerated.

If outcomes provide conclusive safety data, a second funded trial will test the highest tolerated dose of nilotinib vs. placebo, again for safety and tolerability, in 60 people with early-stage Parkinson’s. Neither patients nor investigators will be aware of which treatment is being administered. After 12 months of daily dosing, therapy will be stopped and participants will be monitored for an additional 10 weeks.  

Study leadership is working to secure in-kind donation of drug and placebo for use in the trial.

Relevance to Treatment of Parkinson’s Disease:  The study aims to help researchers determine if nilotinib is safe for use in Parkinson’s disease. The study will also explore nilotinib’s potential to treat symptoms, or to slow or stop disease progression (something no current PD treatment has been proven to do).

Next Steps for Development: Recruitment will begin at clinical sites across the United States in September 2017.

September 2018 Project Update:

The study is being conducted at 25 Parkinson Study Group (PSG) sites in the US. The first participant was recruited in November 2017 and as of July 2018 half of the participants have been randomized into one of the treatment or placebo arms. Recruitment is expected to be completed in late fall 2018 after which participants will be followed through spring/summer 2019.  More details about the trial can be found at www.clinicaltrials.gov (NCT03205488).

September 2019 Project Update:

The study is being conducted at 25 Parkinson Study Group (PSG) sites in the US. The first participant was recruited in November 2017 and as of August 2019 all participants have completed their study visits with top lines results to be reviewed by study leadership in late 2019.

More details about the trial can be found at www.clinicaltrials.gov (NCT03205488).