Trial Outcomes & Findings for Impact of Nilotinib on Safety, Tolerability, Pharmacokinetics and Biomarkers in Dementia With Lewy Bodies (NCT NCT04002674)

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

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

Pharmacodynamics: Determine the effects of Nilotinib on primary biomarkers

Quantification of brain amyloid burden via Florbetaben PET at baseline and 6 months (end of treatment)

Pharmacodynamics: Determine the effects of Nilotinib on CSF levels of Homavanillic Acid (HVA) between baseline and 6 months.

Pharmacodynamics: Determine the effects of Nilotinib on the ratio change of phospho-Tau(181)/Abeta42 (pTau(181)/Ab42) in DLB patients

The MoCA is designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains, including attention and concentration, executive functions, memory, language, visuo-constructional skills, conceptual thinking, calculations and orientation. Scores range between 0 and 30; a score of 26 or higher is generally considered normal, while lower scores indicate impairment.

The Trail Making Test (TMT) is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning. The time to complete the test is measured in seconds. Lower times indicate better executive function, while higher scores suggest impairment.

The 14-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog14) measures cognitive impairment, with higher scores (0-90) indicating greater disability.

ADCS-ADL is an activity of daily living inventory to assess functional performance. Using a structured interview format, study partners are queried as to whether participants attempted each item in the inventory during the prior 4 weeks and their level of performance. The ADCS-ADL includes some items from traditional basic ADL tests as well as instrumental (complex) activities of daily living. It is a 23 item scale that provide a total score from 0-78 with a lower score indicating greater severity.

The Neuropsychiatric Inventory (NPI) is a test widely used, clinician-administered tool that evaluates 12 behavioral domains in dementia patients (e.g., agitation, depression, delusions). Each item is scored by multiplying frequency (1-4) by severity (1-3), resulting in a maximum total score of 144, with higher scores indicating greater neuropsychiatric symptoms, often aligning with disease progression. Minimum Score is 0 (no behavioral symptoms present); maximum Score is 144 (highest severity and frequency across all 12 domains). Higher scores indicate a higher frequency and greater severity of neuropsychiatric symptoms (such as delusions, agitation, or apathy) while lower scores indicate few or no behavioral and psychiatric symptoms.

The CAF consists of seven items of confusional behavior (falls, fluctuation, drowsiness, attention, disorganized thinking, altered level of consciousness, communication), scores for which are summed to provide a severity score for fluctuating confusion ranging from 0 to 21. Higher scores indicate more severe fluctuations while lower scores indicate less severe fluctuations.

The IAS measures apathy and irritability in patients with dementia. The IAS is a 14-item self-administered questionnaire collecting information about different aspects of irritability and apathy utilizing a 0-3 scale for each item to indicate severity (0 (absent) to 3 (maximum intensity) per question). Total Range is 0-42; a higher total score indicates more severe symptoms, which are often associated with greater morbidity and worse functional outcomes while a lower score indicates lower severity.

PBA-s is a structured interview in which a trained interviewer rates the frequency and severity of neuropsychiatric symptoms through observation and the reporting of the Subject and Study Partner. Symptoms rated include depressed mood, suicidal ideation, anxiety, irritability, angry or aggressive behavior, apathy, perseverative thinking or behavior, obsessive-compulsive behaviors, delusional or paranoid thinking, hallucinations, and disoriented behavior. Each behavioral problem is rated for both severity and frequency on a 0-4- point scale; severity and frequency ratings are then multiplied to provide an overall score for each symptom. Minimum score is 0 (symptom is absent); maximum score is 176 (11 items × maximum severity 4 × maximum frequency 4). Higher scores indicate increased frequency or severity of behavioral issues while lower scores indicate decreased severity and frequency.

UPDRS-I-III is used to follow the longitudinal course of Parkinson's disease. The UPDRS is made up of these sections: Part I: evaluation of mentation, behavior, and mood. Part II: self-evaluation of the activities of daily life (ADLs) Part III: clinician-scored monitored motor evaluation. Part IV: complications of therapy. Part V: Hoehn and Yahr staging of severity of Parkinson's disease. The minimum possible score on the UPDRS is 0, which indicates no disability or no symptoms of Parkinson's disease. The scale, used to assess severity, typically ranges from 0 to 199 (total) (199 being the maximum) or 0 to 108 (motor section, Part III) (108 being maximum). Higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) Parts I-III indicate increased severity of disease, greater disability, and more significant impairment, while lower scores signify better function.

Timed Up and Go (TUG) is an assessment of mobility, balance, walking ability, and fall risk. It measures the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down. This assessment is measured in seconds. A score of less than 10 seconds is normal, 14-20 seconds indicates a high fall risk or frailty, and over 30 seconds suggests significant mobility impairment.