Dementia With Lewy Bodies
Conditions
Keywords
Dementia
Brief summary
Multi-center, randomized, double-blind, placebo-controlled, 6- month study in subjects with mild to moderate Dementia with Lewy Bodies.
Detailed description
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.
Interventions
DRUGCT1812
Orally administered CT1812
Sponsors
Cognition Therapeutics
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-blind, placebo-controlled
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
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: 1. Other primary degenerative dementia (fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.). 2. Other neurodegenerative condition (amyotrophic lateral sclerosis, etc.). 3. Seizure disorder. 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Up to 210 Days | All adverse events (AE) summaries were restricted to TEAEs, which were defined as those AEs that occurred on or after the date of first dose and those existing AEs that worsened during the study. If it could not be determined whether the AE was treatment-emergent due to a partial onset date, then it was counted as such. Verbatim terms were mapped to System Organ Class (SOC) and preferred terms using MedDRA version 24.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Montreal Cognitive Assessment Scale (MoCA) | Baseline, Day 28, Day 98, and Day 182 | MOCA is a dementia screening assessment with a 0-30 range with lower scores meaning more impairment |
| Epworth Sleepiness Scale (ESS) | Baseline, Day 28, Day 98, and Day 182 | 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) Total score sums up all sub-scores and can range from 0 to 24. A higher score is associated with increased sleepiness. An ESS score ≥10 is considered abnormal and consistent with excessive daytime sleepiness An ESS score \> 10 is considered consistent with excessive daytime sleepiness |
| Clinician Assessment of Fluctuation (CAF) | Baseline, Day 28, Day 98, and Day 182 | Assessment of cognitive fluctuations, with range of 1-16, with higher scores representing more severe fluctuations |
| Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) | Day 28, Day 98, and Day 182 | The ADCS-CGIC is a 7-point scale similar to other global change scales, where a higher score indicates marked improvement. The 7 responses and corresponding numeric scores for each response of the ADCS-CGIC are: Marked improvement (1), Moderate improvement (2), Minimal improvement (3), No change (4), Minimal worsening (5), Moderate worsening (6), Marked worsening (7). The observed scores at each visit were summarized. A responder was defined as a participant who responded as "Marked improvement, Moderate improvement, Minimal improvement, No change" and non-responder was defined as a participant who responded as "Minimal worsening, Moderate worsening, Marked worsening." |
| ADCS - Activities of Daily Living (ADCS-ADL) | Baseline, Day 28, Day 98, and Day 182 | Assessment of functional impairment in activities of daily living. The total score range is from 0-78 with lower scores indicating greater functional impairment. |
| Movement Disorder Society - United Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III) | Baseline, Day 28, Day 98, and Day 182 | 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 |
| Change From Baseline in the Power of Attention Composite Score of the Cognitive Drug Research (CDR) System Battery | Baseline and Day 182 | The CDR tests are designed to evaluate the effects of novel compounds on the quality of cognitive functioning which includes tests of attention (simple and choice reaction time, digit vigilance), working memory (spatial and numeric) and episodic memory (word recognition, picture recognition).Power of Attention is a composite score derived from the CDR that measures the intensity of concentration (i.e., the ability to focus attention). Faster responses indicate that greater cognitive processing resources are being applied to the task. Power of Attention is calculated as the sum of three cognitive function speed tests: simple reaction time, choice reaction time, and digit vigilance. Scores range from 450 milliseconds (msec) to 61,500 msec. Lower scores reflect faster reaction times and greater intensity of concentration. An increase from baseline, resulting in higher values, indicates worsening compared to the baseline assessment. |
| Neuropsychiatric Inventory (NPI-12) - Domain: Total Score A-L (Frequency x Severity) | Baseline, Day 28, Day 98, Day 182 | The Neuropsychiatric Inventory (NPI) was used to assess common neuropsychiatric symptoms associated with dementia. A structured caregiver interview was conducted to evaluate 12 behavioral domains, including delusions, hallucinations, dysphoria, euphoria, anxiety, agitation/aggression, apathy, irritability/lability, disinhibition, aberrant motor behavior, sleep disturbances, and appetite/eating disorders. Symptom frequency was rated on a 4-point scale (1 = occasionally, 2 = often, 3 = frequently, 4 = very frequently), and symptom severity was rated on a 3-point scale (1 = mild, 2 = moderate, 3 = marked). Domain scores were calculated as the product of frequency and severity ratings. The total NPI score was calculated as the sum of all domain scores and ranges from 0 to 144 (12 domains, each with a maximum score of 12). Increases from baseline (higher scores) indicate worsening of symptoms. |
Countries
United States
Contacts
STUDY_DIRECTORAnthony Caggiano, MD
Cognition Therapeutics Inc.
Participant flow
Recruitment details
Thirty-one sites were selected in the United States: Arizona (2), California (2), Colorado (2), Connecticut (1), Florida (6), Illinois (1), Indiana (1), Kansas (1), Kentucky (1), Massachusetts (1), Minnesota (1), New York (1), North Carolina (1), Ohio (2), Oregon (2), Pennsylvania (1), Texas (1), Virginia (2), and Washington (2).
Pre-assignment details
130 participants met inclusion criteria and were randomized to treatment. The safety population included all participants in the intent-to-treat (ITT) population who received at least one dose of study drug. All 130 randomized participants were included in the ITT population. Participant 113-002, (CT1812 300 mg group), permanently discontinued from the study before study treatment administration due to withdrawal by participant and was not included in the safety population.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 72.8 years STANDARD_DEVIATION 6.69 |
| BMI | 26.5 kg/m^2 STANDARD_DEVIATION 4.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 119 Participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 2 / 43 | 1 / 42 |
| other Total, other adverse events | 42 / 44 | 40 / 43 | 37 / 42 |
| serious Total, serious adverse events | 4 / 44 | 5 / 43 | 8 / 42 |
Outcome results
None listed