Nilotinib in Parkinson's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03205488
• Date of registration: 28/06/2017
• Prospective Registration: Yes
• Primary sponsor: Northwestern University
• Public title: Nilotinib in Parkinson's Disease NILO-PD
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Phase IIa, Parallel Group, Two Cohort Study to Define the Safety, Tolerability, Clinical and Exploratory Biological Activity of the Chronic Administration of Nilotinib in Participants With Parkinson's Disease
• Date of first enrolment: October 16, 2017
• Target sample size: 76
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03205488
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Tanya Simuni, MD
• Affiliation: Northwestern University

Key inclusion & exclusion criteria

Inclusion Criteria; Cohort 1 and 2:

1. Idiopathic PD based on the UK Brain Bank diagnostic criteria.

2. Any race and either gender, age 40-79

3. Able to read and understand English with the capacity to provide voluntary informed
consent by signing the informed consent form (ICF)

4. Willing to comply with all study procedures including multiple lumbar punctures (LP)

5. Must be on a stable regimen of central nervous system acting medications (if
applicable) for at least 30 days prior to the baseline visit (e.g., benzodiazepines,
antidepressants, hypnotics)

Inclusion criteria specific for Cohort 1:

6a. Diagnosis of PD duration > 5 year 7a. Hoehn & Yahr scale (H&Y) stage > 2 and < 4 in the
ON state 8a. Must be on a stable regimen of PD medications, that includes levodopa, for at
least 30 days prior to the screening visit

a. Treatment with monoamine oxidase B (MAO-B) inhibitors will be allowed provided the dose
has been stable for 60 days prior to baseline

Inclusion criteria specific for Cohort 2:

6b. Diagnosis of PD duration < 3 years 7b. H&Y stage = 2 8b. Participants who are currently
NOT receiving symptomatic therapy (ST) (levodopa,dopamine agonists and monoamine oxidase B
(MAO-B) inhibitors) and NOT projected to require ST for at least 3 months from enrollment.

a. Treatment with amantadine or an anticholinergic agent will be allowed provided the dose
has been stable for 30 days prior to screening and will remain stable for the duration of
the study

Exclusion Criteria; Cohorts 1 and 2:

1. Diagnosis of atypical parkinsonism

2. History of bipolar disorder or major depression, or presence of active depression
defined as a Beck Depression Inventory II (BDI-II) score >17

3. History of a suicide attempt within the last 5 years or active suicidal ideations

4. History of schizophrenia or schizophrenia spectrum disorders

5. History of uncontrolled hypokalemia or hypomagnesaemia, or laboratory evidence of such
on screening

6. History of cardiac arrhythmia, long QT syndrome, or a corrected QT interval (QTcF)
=450ms at screening visit 1

7. Treated within 30 days prior to randomization, or planned use during the trial with
any of the following classes of Concomitant drugs:

1. Class IA or III antiarrhythmic drugs

2. QT prolonging drugs

3. Strong CYP3A4 inhibitors or inducers

4. Anticoagulants

5. Proton pump inhibitors

8. A clinical history, or the active presence of a cardiovascular condition including:

1. Myocardial infarction, known cardiac ischemia, or angina

2. Cerebrovascular event (e.g. embolic stroke)

3. Congestive heart failure, symptomatic first degree atrioventricular (AV) block or
PR interval > 220msec and all second and third degree AV block, second- or
third-degree atrioventricular block, sick sinus syndrome, or other serious
cardiac rhythm disturbances

4. History of Torsade de Pointes

5. Other cardiovascular history that, in the opinion of the Site Investigator, will
preclude study participation

9. History of hepatic disease, including abnormal liver function defined as Total
Bilirubin > 1.5 times upper limit, Aspartate Aminotransferase (AST) and/or Alanine
Aminotransferase (ALT) > 2 times the upper limit of the normal, or coagulopathy with
INR > 1.4

10. History of epilepsy or a seizure within the last 6 months

11. Active malignancy, or history of a neoplasm in the prior 5 years (excluding
basal/squamous cell carcinoma)

12. Prior history of pancreatitis or total gastrectomy or evidence of abnormal pancreatic
function defined as elevated amylase and/or lipase > 2 times upper limit of normal

13. Diagnosis of human immunodeficiency virus (HIV), clinically significant chronic
hepatitis such as hepatitis B (HBV) or hepatitis C (HCV), or clinical history or signs
of an active infection

14. History of drug or alcohol abuse = 5 years

15. Active medical or psychiatric condition that in the opinion of the Site Investigator
should preclude study participation

16. Previous surgical management for PD

17. Participants participating in any drug or device clinical investigation concurrently
or within 30 days prior to screening for this study

18. Severe lactose and galactose intolerance

19. Participants with evidence of other significant laboratory abnormalities which in the
opinion of the site investigator or clinical monitor should preclude study
participation

20. Known hypersensitivity or contraindication to study drugs (nilotinib or matching
placebo) or their components.

21. Female participants of child-bearing potential. Female participants must be
post-menopausal, post-hysterectomy, or have a documented infertility based on a known
medical or surgical condition

22. Participants with a history of bone marrow suppression or evidence of persistent
myelosuppression defined as absolute neutrophil count <1.8 X 109/L, significant
anemia, or thrombocytopenia defined as platelet count < 100 X 109/L

Exclusion criteria specific for Cohort 1:

22a. Diagnosis of dementia based on the clinician's assessment, or a Montreal Cognitive
Assessment (MoCA) score < 21 at baseline

Exclusion criteria specific for Cohort 2:

22b.MoCA score < 26 at baseline 23b. Treated within 60 days prior to randomization or
expected to require treatment within 3 months from randomization with any ST (including
levodopa and dopamine agonists )

a. Treatment with amantadine or an anticholinergic agent will be allowed provided the dose
has been stable for 30 days prior to screening and will remain stable for the duration of
the study



Age minimum: 40 Years
Age maximum: 79 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Drug: Cohort 2: Nilotinib Oral Capsules (dose to be determined from Cohort 1)

Drug: Cohort 1:Nilotinib Oral Capsules (150mg or 300mg)

Drug: Placebo

Primary Outcome(s)

Tolerability of Nilotinib Over Placebo [Time Frame: 6 months]

Safety of Nilotinib [Time Frame: We assessed adverse events that were collected from the first dose of study drug until 60 days after the participant's last dose.]

Secondary Outcome(s)

Change in MDS-UPDRS Part III [Time Frame: The MDS-UPDRS Part III ON state was collected at baseline, day 14, day 30, month 3, month 6, 30 and 60 days post treatment. The OFF state was collected at baseline, month 3, month 6, 30 and 60 days post treatment.]

Secondary ID(s)

NILO-PD

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Iowa

University of Rochester

Michael J. Fox Foundation for Parkinson's Research

Results

• Results available: Yes
• Date Posted: 22/07/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03205488