AzTrials
AzTrials

Dementia With Lewy BodiesPhase 2NCT03888222

Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies

A Phase 2 study testing Bosutinib Oral Tablet in people with Dementia With Lewy Bodies, run by Georgetown University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study evaluates the effect of Bosutinib (Bosulif,Pfizer®) in the treatment of patients with Dementia with Lewy Bodies. Half participants will receive 100 mg of Bosutinib , while the other half will receive placebo. Read more about this study

Who is it for?
Ages 25 to 90 years
Conditions the study is for
Dementia With Lewy Bodies
What is being tested?
Bosutinib Oral Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
26 participants
Where
1 siteUnited States
Study dates
23 Apr 2019to 27 Aug 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • Age of 25-90 years, medically stable
  • 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 ≤ 50 and UPDRS-III between 20-40.
  • Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD)
  • Abnormal DaTScan
Show all 11Show fewer
  • Stable on Levodopa no more than 800mg daily, acetylcholinesterase inhibitors, dopamine agonists for at least 6 weeks
  • Stable on monoamine oxidase inhibitors (MOA-B) for at least 4 weeks before enrollment
  • Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI
  • QTc interval 350-480 ms, inclusive
  • Participants must be willing to undergo LP at baseline and 3 months after treatment.

Who cannot join

  • Medical history of liver or pancreatic disease, GI ulcers and Chron's disease, kidney, GI, or blood problems
  • 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 or proteinuria
  • History of HIV, clinically significant chronic hepatitis, or other active infection
  • hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥480 ms or concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infarction or cardiac failure, angina, arrhythmia
  • History or presence of significant 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.
Show all 15Show fewer
  • 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 SSRIs (e.g. Citalopram, Escitalopram, Paroxetine, Sertraline, Duloxetine, Trazodone, 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. Should treatment with any of these agents be required, therapy with Bosutinib should be interrupted. Anticoagulants, including Coumadin (warfarin), heparin, enoxaparin, daltiparin, xeralto, 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 Bosutinib
  • Females must not be lactating, pregnant or with possible pregnancy
  • Clinical signs indicating syndromes other than DLB including, Alzheimer's Disease (AD) idiopathic PD, corticobasal degeneration, supranuclear gaze palsy, multiple system atrophy, chronic traumatic encephalopathy, signs of frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, Babinski sign
  • Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any active major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
  • Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory abnormality.
  • Active neoplastic disease, history of cancer five years prior to screening, including breast cancer (history of skin melanoma or stable prostate cancer are not exclusionary)
  • Contraindications to LP: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets < 100,000, use of Coumadin/warfarin, or history of a bleeding disorder.
  • Must not be on any immunosuppressant medications
  • Must not be enrolled as an active participant in another clinical study.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies (DLB)

This study evaluates the effect of Bosutinib (Bosulif,Pfizer®) in the treatment of patients with Dementia with Lewy Bodies. Half participants will receive 100 mg of Bosutinib , while the other half will receive placebo.

Read the detailed description

This proposal will evaluate the effects of Bosutinib (Bosulif, Pfizer®) treatment - an FDA-approved tyrosine kinase inhibitor that targets c-Abelson (Abl) and Src tyrosine kinases- in patients with DLB. Investigators have demonstrated safety and efficacy of this compound in pre-clinical animal models and others have shown similar benefits of Bosutinib on inflammation and neurotoxic protein clearance in neurodegeneration. Investigators have demonstrated that Bosutinib enters the brain (5% CSF:plasma ratio) and inhibits Abl at lower doses (5mg/kg) than the cancer dose (80mg/kg) in animals. Bosutinib also reduces the levels of neurotoxic proteins including alpha-synuclein, tau and beta-amyloid and improves motor and cognitive behavior in models of neurodegeneration. The use of Bosutinib is a novel strategy that promotes autophagy to clear neurotoxic protein aggregates in neurons. Bosutinib is FDA-approved for the treatment of chronic myelogenous leukemia (CML) at an oral dose of 400-600 mg daily. Based on our preclinical evidence, investigators used allometric conversion to extrapolate animal to human dose and estimated a human equivalent dose daily dose of 100mg Bosutinib in this clinical study to determine the safety and tolerability, pharmacokinetics and pharmacodynamics in patients with mild to moderate DLB.

Being tested
Placebo Oral Tablet, Bosutinib Oral Tablet
Medical subject headings
Lewy Body Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Placebo Oral TabletDrug

    Also called Placebo

    Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .

  • Bosutinib Oral TabletDrug

    Also called Bosutinib(Bosulif®, SKI-606, Pfizer)

    Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .

Study groups in NCT03888222
Study groupRoleWhat they receive
PlaceboPlacebo comparatorThirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Receives: Drug: Placebo Oral Tablet
100 mg of BosutinibActive comparatorThirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Receives: Drug: Bosutinib Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.

    We will determine safety and tolerability using the occurrence of adverse events (AEs) of interest, including myelosuppression, urinary, pancreatic and hepatic disorders, QTc prolongation as per Bosutinib IB.

    Measured: 12 weeks

Secondary outcomes (9)
  1. Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases

    Phospho-ABL(PanTyr) and phospho-SRC(Y416) are critical drivers in the pathogenesis of various neurodegenerative diseases. We will examine the changes in CSF and Plasma phospho-ABL(PanTyr) and phospho-SRC(Y416) absorbance (ABS) levels at baseline and 3 months. The magnitude of the absorbance is proportional to the quantity of tyrosine-phosphorylated protein.

    Measured: Change between baseline (BSL) and Week-12

  2. Determine the Maximum Concentration (Cmax) (ng/ml) of Bosutinib in the CSF and Plasma.

    To determine the Cmax (ng/ml), we will measure Bosutinib in both the CSF and Plasma using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)

    Measured: 12 weeks

  3. Determine the Maximum Concentration (Cmax) (nM) of Bosutinib in the CSF and Plasma.

    To determine the Cmax (nM), we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)

    Measured: 12 weeks

  4. Determine the Maximum Time (Tmax) Bosutinib Peaks in CSF and Plasma.

    To determine the Tmax, we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)

    Measured: 12 weeks

  5. Determine the Area Under the Curve (AUC) (ng/ml*Hours) for Bosutinib in CSF and Plasma.

    To determine the AUC (ng/ml*hours) , we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)

    Measured: 12 weeks

  6. Determine the Area Under the Curve (AUC) (nM*Hours) for Bosutinib in CSF and Plasma.

    To determine the AUC (nM*hours) , we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)

    Measured: 12 weeks

  7. Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers

    We will examine the changes in CSF and Plasma Abeta40, Abeta42, total tau, ptau181 and total and oligomeric alpha-synuclein at baseline, week-12, and the change between baseline and week-12.

    Measured: Change between baseline (BSL) and Week-12

  8. Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers

    We will examine the ratio changes in CSF and Plasma AB42 to AB40, ptau(181 )to AB42, pTau(181) to tTau, aggregated a-syn to total a-syn at baseline, 12 weeks, and between baseline and week-12.

    Measured: 12 weeks

  9. Measure HVA and DOPAC in CSF and Plasma

    We will measure the levels of DOPAC AND Homovanillic Acid (HVA) using liquid-liquid extraction and Liquid chromatography-tandem mass spectrometry (LC-MS/MS) in CSF and plasma samples at baseline (BSL), 12 weeks, and between baseline and 12 weeks (WK12).

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Mar 2019
  2. Study start23 Apr 2019
  3. Primary completion27 Aug 2021
  4. Study completion27 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
We will evaluate the effects of 100 mg Bosutinib versus matching placebo taken daily by mouth for 12 weeks, followed by a 4 week wash-out period in individuals diagnosed with DLB. We will perform physiologically-based population pharmacokinetics (popPK) using a seamless random single dose (RSD) of Bosutinib, where participants (n=30) will be randomized to 3 groups (n=10) and take a single oral dose of 100mg, 200mg, Bosutinib or placebo (1;1;1) open label. Lumbar puncture will be performed between 1-4 hours after dosing. Participants will then be randomized double-blinded into 2 groups 1;1 using placebo(n=15) and 100mg (n=15) for 3 months. Randomization and Registration will be performed by an internet based randomization module. Randomization of the subjects to the 2 treatment groups will be performed in a stratified manner. The chance for randomization to the groups is 1:1 for placebo: 100 mg Bosutinib.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03888222
Sponsor's protocol ID
IRB#: STUDY00000017
Status last verified
Jun 2026
First submitted
13 Mar 2019
Last updated
10 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hebron ML, Lonskaya I, Olopade P, Selby ST, Pagan F, Moussa CE. Tyrosine Kinase Inhibition Regulates Early Systemic Immune Changes and Modulates the Neuroimmune Response in alpha-Synucleinopathy. J Clin Cell Immunol. 2014 Sep 30;5:259. doi: 10.4172/2155-9899.1000259.

    PubMed 25635231

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bosutinib Oral Tablet in people with Dementia With Lewy Bodies, run by Georgetown University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03888222, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in