NCT03888222

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

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)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Georgetown University · Academic / Other
• Sex: All
• Age: 25 Years – 90 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Dementia With Lewy Bodies

Interventions

Type	Name	Description
DRUG	Placebo Oral Tablet	Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
DRUG	Bosutinib Oral Tablet	Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .

Timeline

• Start date: 2019-04-23
• Primary completion: 2021-08-27
• Completion: 2021-08-27
• First posted: 2019-03-25
• Last updated: 2022-04-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study