Trial Outcomes & Findings for Study to Evaluate the Safety, Tolerability and Efficacy of CT1812 in Subjects With Mild to Moderate Dementia With Lewy Bodies (NCT NCT05225415)

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).

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.

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

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.

MOCA is a dementia screening assessment with a 0-30 range with lower scores meaning more impairment

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

Assessment of cognitive fluctuations, with range of 1-16, with higher scores representing more severe fluctuations

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."

Assessment of functional impairment in activities of daily living. The total score range is from 0-78 with lower scores indicating greater functional impairment.

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

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.

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.