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Nilotinib in Parkinson's Disease (NILO-PD)

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ClinicalTrials.gov Identifier: NCT03205488
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : January 18, 2018
Sponsor:
Collaborators:
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Cohort 1:Nilotinib Oral Capsules (150mg or 300mg) Drug: Cohort 2: Nilotinib Oral Capsules (dose to be determined from Cohort 1) Drug: Placebo Phase 2

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).


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 16, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Nilotinib
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Cohort 1
Moderate to Advanced PD Population Randomized 1:1:1
Drug: Cohort 1:Nilotinib Oral Capsules (150mg or 300mg)
2 capsules taken once daily
Drug: Cohort 2: Nilotinib Oral Capsules (dose to be determined from Cohort 1)
2 capsules taken once daily
Active Comparator: Cohort 2
Early/de novo Randomized 2:1
Drug: Cohort 2: Nilotinib Oral Capsules (dose to be determined from Cohort 1)
2 capsules taken once daily
Drug: Placebo
2 capsules taken once daily


Outcome Measures

Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Cohort 1 = 6 months, Cohort 2 = 12 months ]
    the frequency of treatment-related serious adverse events across all groups within each cohort

  2. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Cohort 1 = 6 months, Cohort 2 = 12 months ]
    The ability to complete the study on the assigned dose


Secondary Outcome Measures :
  1. Motor Function [ Time Frame: 6 months ]
    Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (motor function) will be evaluated to determine if Nilotinib has the potential to reduce the MDS-UPDRS motor score.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 79 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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

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 or suicidal ideations
  4. History of schizophrenia or schizophrenia spectrum disorders
  5. History of hypokalemia or hypomagnesaemia, or laboratory evidence of such on screening
  6. History of cardiac arrhythmia, long QT syndrome, or a corrected QT interval (QTc) ≥450ms at baseline
  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, first, 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 Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) > 2 times the upper limit of the normal
  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
  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
  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. Treatment with MAO-B inhibitors 60 days prior to randomization and for the duration of the study
  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

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, dopamine agonists and MAO-B inhibitors)

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03205488


Contacts
Contact: Tina Ward, MS 877-483-1834 NILO_STUDY@chet.rochester.edu

  Show 25 Study Locations
Sponsors and Collaborators
Northwestern University
University of Rochester
University of Iowa
Michael J. Fox Foundation for Parkinson's Research
Investigators
Principal Investigator: Tanya Simuni, MD Northwestern University
More Information

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT03205488     History of Changes
Other Study ID Numbers: NILO-PD
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: January 18, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Northwestern University:
Northwestern
Nilotinib
USA
NILO-PD
Parkinson Disease

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases