Nilotinib in Parkinson's Disease (NILO-PD)

July 21, 2020 updated by: Tanya Simuni, Northwestern University

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
76

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-0017
        • University of Alabama at Birmingham
    • Arizona
      • Sun City, Arizona, United States, 85013
        • Barrow Neurological Institute
    • California
      • Sacramento, California, United States, 95817
        • University of California Davis
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado at Denver
    • Florida
      • Gainesville, Florida, United States, 32607
        • University of Florida
      • Tampa, Florida, United States, 33620
        • University of South Florida
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21093
        • John Hopkins University
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • East Lansing, Michigan, United States, 48824
        • Michigan State University
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Cleveland Clinic - Las Vegas
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical College
      • New York, New York, United States, 10003
        • Beth Israel Medical Center
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • University of Pennsylvania
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia
    • Washington
      • Spokane, Washington, United States, 99202
        • Inland Northwest Research
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 79 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: Placebo
2 capsules taken once daily
ACTIVE_COMPARATOR: Cohort 2
Early/de novo Randomized 2:1
Drug: Placebo
2 capsules taken once daily
Drug: Cohort 2: Nilotinib Oral Capsules (dose to be determined from Cohort 1)
2 capsules taken once daily

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Tolerability of Nilotinib Over Placebo
Time Frame: 6 months
The count of study participants who completed the 6-month study treatment period while active on their original assigned dose
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.
The count of study participants who experienced any treatment-related SAE in each treatment group
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III is a motor examination in both practically defined medications OFF state (12 hrs post dose) and ON state (based on the participant/site investigator defined best ON and/or approximately 1 hour post dose). Measure Description: The part III subscale score ranges from 0-165. The Larger the value stands for more disability from PD.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Northwestern University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Iowa
University of Rochester
Michael J. Fox Foundation for Parkinson's Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 16, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 26, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 28, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 28, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 2, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 21, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NILO-PD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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