Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Dementia With Lewy Bodies

NCT04002674 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00000122
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Dementia with Lewy Bodies (DLB) is an alphasynucleinopathy and the second most common form of dementia in the elderly. DLB shares striking neuropathological and clinical similarities with both Parkinson's disease (PD) and Alzheimer's disease (AD). Nilotinib (Tasigna®, AMN107, Novartis, Switzerland) is approved by the FDA and is well tolerated for CML treatment at oral doses of 600-800mg daily. The Investigators propose to perform a phase II randomized, double blinded, placebo controlled study to evaluate the impact of Nilotinib in patients with DLB.

Conditions

Dementia With Lewy Bodies

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability: Occurrence of Adverse Events (AEs)

  The Investigators will determine safety and tolerability using the occurrence of adverse events (AEs) of interest as per Nilotinib Investigator Brochure (IB).

  6 Months

Secondary Outcomes (4)

• DLB Related CSF Biomarkers

  6 Months

• The Investigators Will Quantify Amyloid Burden Via Florbetaben PET Scan

  Baseline, 6 Months, and change between baseline and 6 months

• DLB Related CSF Biomarkers

  Changes from Baseline to 6 months

• DLB Related CSF Biomarkers

  6 months

Other Outcomes (10)

• Measure the Effects of Nilotinib on Cognition Using the Montreal Cognitive Assessment (MoCA)

  Change from Baseline in the Montreal Cognitive Assessment at 6 months

• Measure the Effects of Nilotinib on Cognition Using the Trail Making Test (TMT)

  Change from Baseline in the Trail Making Test at 6 months

• Measure the Effects of NIlotinib on Cognition Using the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog14).

  Change from Baseline in the Alzheimer's Disease Assessment Scale - cognitive at 6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Sixty (60) participants will be recruited and randomized into 2 arms (1:1). Thirty (30) patients in arm 1 will receive the matching placebo ("sugar pill") one (1) capsule orally (without food) once daily for 6 months (180 days).

Drug: Placebo oral capsule

200 mg Nilotinib

ACTIVE COMPARATOR

Sixty (60) participants will be recruited and randomized into 2 arms (1:1). Thirty (30) patients in arm 2 will receive the 200 mg of Nilotinib one (1) capsule orally (without food) once daily for 6 months (180 days).

Drug: Nilotinib Oral Capsule

Interventions

Placebo oral capsule DRUG

Thirty (30) patients in arm 1 will receive the matching placebo ("sugar pill") one (1) capsule orally (without food) once daily for 6 months (180 days).

Also known as: Placebo

Placebo

Nilotinib Oral Capsule DRUG

Thirty (30) patients in arm 2 will receive the 200 mg of Nilotinib one (1) capsule orally (without food) once daily for 6 months (180 days).

Also known as: Tasigna

200 mg Nilotinib

Eligibility Criteria

• Age: 25 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR).
• Clinical diagnosis of DLB according to McKeith et al (7) with both dementia MoCA≥18 and Parkinsonian defined as bradykinesia in combination with rest tremor, rigidity or both UPDRS I-III is less than 50 and/or UPDRS-III between 15 -40 on-state. Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD)
• ≥Hoehn and Yahr stage ≤3
• MDS-UPDRS-III 15-40 on-state (or up to 70 on the off state)
• Abnormal DaTScan
• Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI
• Patients between the age of 25-90 years, medically stable
• Must NOT be stable on mono-amine oxidase (MAO)-B inhibitors (Selegeline or rasagiline) for at least 4 weeks before enrollment and during Nilotinib treatment.
• Must be medically stable on less than or equal to 800mg Levodopa daily for at least 4 weeks
• QTc interval 350-460 ms, inclusive
• Participants must be willing to undergo LP at baseline and 6 months after treatment

You may not qualify if:

• Patients with hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥461 ms
• Concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infraction or cardiac failure, angina, arrhythmia
• History or presence of cardiac conditions including:
• Cardiovascular or cerebrovascular event (e.g. myocardial infarction, unstable angina, or stroke)
• Congestive heart failure
• First, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances
• Any history of Torsade de Pointes
• Treatment with any of the following drugs at the time of screening or the preceding 30 days, and/or planned use over the course of the trial:
• Treatment with Class IA or III antiarrhythmic drugs (e.g. quinidine)
• Treatment with QT prolonging drugs (www.crediblemeds.org)- excluding Selective Serotonin Reuptake Inhibitors (SSRIs) (e.g. Citalopram, Paxil, Zoloft, Cymbalta, Sertraline, etc...)
• Strong CYP3A4 inhibitors (including grapefruit juice). The concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) must be avoided. Grapefruit products may also increase serum concentrations of Nilotinib. Should treatment with any of these agents be required, therapy with Nilotinib should be interrupted.
• Anticoagulants, including Coumadin (warfarin), heparin, enoxaparin, daltiparin, xarelto, etc.
• St. John's Wort and the concomitant use of strong other CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) must be avoided since these agents may reduce the concentration of Nilotinib.
• Abnormal liver function defined as AST and/or ALT \> 100% the upper limit of the normal
• Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal

Sponsors & Collaborators

• Georgetown University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (1)

• Hebron ML, Lonskaya I, Moussa CE. Nilotinib reverses loss of dopamine neurons and improves motor behavior via autophagic degradation of alpha-synuclein in Parkinson's disease models. Hum Mol Genet. 2013 Aug 15;22(16):3315-28. doi: 10.1093/hmg/ddt192. Epub 2013 May 10.

  PMID: 23666528 RESULT

Related Links

• https://sites.google.com/a/georgetown.edu/moussa-lab/lab-members

MeSH Terms

Conditions

Lewy Body Disease

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Fernando Pagan
• Organization: Georgetown University Hospital

Fernando.L.Pagan@gunet.georgetown.edu

202-444-6087

Study Officials

• Fernando L Pagan, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomized by a Biostatistician by an internet based randomization module into two groups. The researchers include : Primary investigator , Sub-Investigators ,Clinical Coordinators, Nurse Practitioners , and Clinical Reseach unit staff.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Neurology Co-Director, Movement Disorders Program Director, NPF Center of Excellence Associate Professor, SOM Clinical Track

Model Details: Investigators will evaluate the effects of 200 mg of Nilotinib versus matching Placebo taken daily by mouth for 6 Months, followed by 1 Month wash-out period in individuals with DLB. Sixty (60) participants will be recruited and randomly assigned 1:1 to placebo (arm 1) or 200 mg Nilotinib (arm 2). Participants will be treated for 6 months and monitored every month (4 weeks) in a total of 9 visits that include screening, baseline, 1, 2, 3, 4, 5, 6 months follow up and 7-month washout.

Study Record Dates

• First Submitted: April 8, 2019
• First Posted: June 28, 2019
• Study Start: July 1, 2019
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: June 12, 2026
• Results First Posted: April 3, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)