Nilotinib in Parkinson's Disease

NCT ID: NCT03205488

Last Updated: 2020-07-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-16
• Study Completion Date: 2019-09-28

Brief Summary

This study will assess the safety and tolerability of daily oral administration of nilotinib (150-300mg once daily) in Parkinson's Disease.

Detailed Description

The purpose of this study is to determine if nilotinib is safe, if it can be tolerated by patients with Parkinson's disease (PD) and to learn if nilotinib has the possibility of effectively treating PD symptoms. Nilotinib has been approved by the Food and Drug Administration (FDA) to treat certain types of cancer (leukemia) but is considered investigational in this study because it has not been approved for treating PD. Twenty-five sites will enroll participants into 2 cohorts,approximately 75 in Cohort 1 and 60 in Cohort 2. Participants with moderate to advanced PD symptoms will be enrolled in Cohort 1, randomly assigned to take nilotinib (150 mg or 300mg) or placebo, and will complete 13 in-person study visits over 8.5 months.

The results from Cohort 1 will determine if either dose of nilotinib (150mg or 300 mg) is safe and tolerable enough to move forward and evaluate in Cohort 2. If either dose is found to be safe and tolerable, participants with early PD will be enrolled into Cohort 2.

Participants in Cohort 2 will be randomly assigned to either nilotinib (dose to be determined from Cohort 1 results) or placebo and will complete 17 in-person visits over 14.5 months. For both cohorts, the study visits will include clinical assessment of motor, neuropsychiatric and cognitive testing as well as collection of blood and cerebral spinal fluid, collected by lumbar puncture.

This study will also evaluate if nilotinib can help improve motor symptoms associated with PD. All participants in Cohort 1 and participants in Cohort 2 who have started PD medications will have an assessment of the motor exam (Part III) in a practically defined OFF state (12 hours post dose) and ON state (at least one-hour post dose).

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Cohort 1

Moderate to Advanced PD Population Randomized 1:1:1

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DRUG

2 capsules taken once daily

Placebo

Intervention Type: DRUG

2 capsules taken once daily

Cohort 2

Early/de novo Randomized 2:1

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DRUG

2 capsules taken once daily

Placebo

Intervention Type: DRUG

2 capsules taken once daily

Interventions

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

2 capsules taken once daily

Intervention Type: DRUG

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

2 capsules taken once daily

Intervention Type: DRUG

Placebo

2 capsules taken once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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)

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

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

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

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

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Rochester

OTHER

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Tanya Simuni

Director, Parkinson's disease and Movement Disorders Center Northwestern University Feinberg School of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tanya Simuni, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Barrow Neurological Institute

Sun City, Arizona, United States

University of California Davis

Sacramento, California, United States

University of Colorado at Denver

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

University of South Florida

Tampa, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

John Hopkins University

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Michigan State University

East Lansing, Michigan, United States

Cleveland Clinic - Las Vegas

Las Vegas, Nevada, United States

Albany Medical College

Albany, New York, United States

Beth Israel Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Baylor College of Medicine

Houston, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Inland Northwest Research

Spokane, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Joshi D, Kulkarni M, Parekh P, Shah S, Greig NH, Acharya S. Targeting protein kinases in Parkinson's disease: the emerging role of phytoconstituents. Nutr Neurosci. 2025 Jul 18:1-32. doi: 10.1080/1028415X.2025.2531356. Online ahead of print.

Reference Type: DERIVED

PMID: 40680102 (View on PubMed)

Simuni T, Fiske B, Merchant K, Coffey CS, Klingner E, Caspell-Garcia C, Lafontant DE, Matthews H, Wyse RK, Brundin P, Simon DK, Schwarzschild M, Weiner D, Adams J, Venuto C, Dawson TM, Baker L, Kostrzebski M, Ward T, Rafaloff G; Parkinson Study Group NILO-PD Investigators and Collaborators. Efficacy of Nilotinib in Patients With Moderately Advanced Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2021 Mar 1;78(3):312-320. doi: 10.1001/jamaneurol.2020.4725.

Reference Type: DERIVED

PMID: 33315105 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

NILO-PD

Identifier Type: -

Identifier Source: org_study_id