Study to Evaluate the Safety, Tolerability and Efficacy of CT1812 in Subjects With Mild to Moderate Dementia With Lewy Bodies

Study Overview
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Brief Summary
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Multi-center, randomized, double-blind, placebo-controlled, 6- month study in subjects with mild to moderate Dementia with Lewy Bodies.

Detailed Description
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The safety and efficacy of CT1812 at doses of 300 and 100mg will be evaluated over a 24 week double-blind treatment period in patient diagnosed with dementia with Lewy bodies. Patients will be randomized 1:1:1 to placebo, 100mg CT1812 or 300mg CT1812. Oral CT1812 will be taken daily. Subjects meeting eligibility requirement and signing informed consent will be assessed by repeated psychometric/neurologic testing, safety procedures and PK and PD sample collection at defined intervals throughout the study. Plasma and CSF biomarkers will also be followed.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase 2, 6-month Study to Evaluate the Safety, Tolerability and Exploratory Efficacy of CT1812 in Subjects With Mild to Moderate Dementia With Lewy Bodies

Conditions
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Dementia With Lewy Bodies

Intervention / Treatment
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* Drug: CT1812


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women 50-85 years of age (inclusive), meeting criteria for probable Dementia with Lewy Bodies (DLB). MRI, or CT scan due to contraindication of MRI if approved by medical monitor) obtained during screening consistent with the clinical diagnosis of DLB and without findings of significant exclusionary abnormalities. An historical MRI (or CT scan), up to 1 year prior to screening, may be used if there is no history of intervening neurologic disease or clinical events (such as a stroke, head trauma etc.) and the subject is without clinical symptoms or signs suggestive of such intervening events. MMSE 18-27 inclusive Exclusion Criteria: Any neurological condition that may be contributing to cognitive impairment above and beyond those caused by the subject's DLB, including any co-morbidities detected by clinical assessment or MRI (or CT scan due to contraindication of MRI, if approved by medical monitor) Screening MRI (or historical MRI or CT scan due to contraindication of MRI if approved by medical monitor) or historical MRI/CT scan, if applicable. of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct > 1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such as meningioma). If a small incidental meningioma is observed, the medical monitor may be contacted to discuss eligibility. Clinical, laboratory findings or medical history consistent with: Other primary degenerative dementia (fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.). Other neurodegenerative condition (amyotrophic lateral sclerosis, etc.). Seizure disorder. Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, other laboratory values etc.). Any major psychiatric diagnosis, including schizophrenia, bipolar disorder, and current major depressive disorder as per Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Clinically significant, advanced or unstable disease that may interfere with outcome evaluations.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CT1812 300 mg<br>CT1812 300 mg | Drug: CT1812<br>* Orally administered CT1812<br>|
| Active Comparator: CT1812 100 mg<br>CT1812 100 mg | Drug: CT1812<br>* Orally administered CT1812<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: CT1812<br>* Orally administered CT1812<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of CT1812 | Incidence and Severity of Adverse Events | Baseline, Day 1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 98, Day 126, Day 154, Day 182, Day 210 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal Cognitive Assessment Scale (MoCA) | MOCA is a dementia screening assessment with a 0-30 range with lower scores meaning more impairment | Baseline, 3 months, 6 months | 
| Epworth Sleepiness Scale (ESS) | The ESS is an assessment of subjective sleepiness over the prior two weeks. The scale is on 4 point scale (0 = no chance of dozing; 1 = slight chance of dozing; 2 = moderate chance of dozing; 3 = high chance of dozing) An ESS score > 10 is considered consistent with excessive daytime sleepiness | Baseline, 3 months, 6 months | 
| Clinician Assessment of Fluctuation (CAF) | Assessment of cognitive fluctuations, with range of 1-16, with higher scores representing more severe fluctuations | Baseline, 3 months, 6 months | 
| ADCS-Clinical Global Impression of Change (CGIC) | The ADCS-CGIC is a 7-point scale similar to other global change scales, where a higher score indicates marked improvement | Baseline, 3 months, 6 months | 
| ADCS - Activities of Daily Living (ADCS-ADL) | Assessment of functional impairment in activities of daily living. The total score range is from 0-78 with lower scores indicating greater functional impairment. | Baseline, 3 months, 6 months | 
| Movement Disorder Society - United Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III) | This exam covers 18 motor signs associated with parkinsonism covering bradykinesia, rigidity, tremor, and gait with a range of scores from 0-136, with higher scores supporting more severe symptoms. A score of 6 or greater suggest the presence of parkinsonism | Baseline, 3 months, 6 months | 
| Cognitive Drug Research Battery (CDR) | Computerized battery that captures reaction time, cognitive reaction time, vigilance, and power of attention | Baseline, 3 months, 6 months | 
| Neuropsychiatric Inventory (NPI) | Assessment of common behaviors associated with dementia | Baseline, 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia