Neflamapimod

The number and proportion of participants experiencing adverse events (AEs) and serious adverse events (SAEs) during the study period, categorized by severity and relationship to the study intervention.

The FMMS test has a maximum upper motor score of 66, maximum lower motor score of 34, and a maximum total score of 212, where an increase indicates improved motor function while a decrease indicates worsening impairment.

The TUG test is recorded in seconds. The test has no minimum or maximum value, and an increase in the time required to complete the TUG is a worse outcome.

Scores for the NIHSS range from 0 to 42 where higher scores indicate greater impairment/worsening.

The safety and tolerability of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via the incidence of treatment-emergent Adverse events (AEs) and Serious adverse events (SAEs) during 24 weeks of treatment

The safety and tolerability of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via the incidence of elevations in amino-alanine transferase (ALT) and/or aspartate amino-transferase (AST) ≥ three times the upper limit of normal during 24 weeks of treatment

The maximum plasma concentration (Cmax) of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via mean (with 95% confidence interval) plasma drug concentration at steady state during 24 weeks of treatment with neflamapimod 80mg BID.

The trough plasma concentration (Ctrough) of 80 mg neflamapimod given twice daily in patients with dementia with lewy bodies will be evaluated via mean (with 95% confidence interval) plasma drug concentration at steady state during 24 weeks of treatment with neflamapimod 80mg BID.

Evaluate the efficacy of neflamapimod, compared to placebo, as a treatment for DLB, as assessed by the CDR-SB scale. CDR-SB scores range from 0 to 18 with a higher score indicating worsening of cognitive impairment.

Change from Baseline to Week 4, Week 8, and Week 16 in the composite z-score of a study-specific Neuropsychological Test Battery (NTB) that included the following six tests: Cogstate Detection test (DET), Cogstate Identification test (IDN), Cogstate One Card Learning test (OCL), Cogstate One Back test (ONB), Letter Fluency Test, and Category Fluency Test (CFT). Each score on the individual tests was converted to a z-score, and then a total z-score for the composite was calculated, in which each test is weighted equally. As the analysis is based on z-scores, there is no minimum or maximum value. A z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A positive change in z-score indicate an improvement in cognition, i.e., a better outcome; and a negative change in z-score indicates a worsening in cognition, i.e., a worse outcome.

Combined change from baseline in z-scores of total and delayed recall on the Hopkins Verbal Learning Test - Revised (HVLT-R) in neflamapimod-treated subjects compared to placebo. The primary endpoint was analyzed using Mixed Model for Repeated Measures (MMRM) with fixed effects for treatment, background AD-specific therapy, CDR-Global Score of 0.5 versus 1.0, scheduled visit (nominal) and scheduled visit by treatment interaction, random effect for subject and baseline Z-score as a covariate. For baseline total and delayed recall, a z-score for each subject is defined by z=(x-m)/s where x is the subject's recall at baseline, and m and s are the overall mean and overall standard deviation of recall at baseline across all subjects. A composite baseline z-score for each subject is calculated using equal weighting in the following way: Z=0.5\*z-score for total recall at baseline + 0.5\*z-score for delayed recall at baseline. For HVLT-R, higher score indicates improvement.

Percent change in global cortical amyloid specific PET signal (BPND)

Number of patients meeting protocol pre-specified definition of response: \> 7% reduction in global cortical BPND

Cytokines: Of nine cytokines assessed, only CSF IL-8 quantifiable at all time points. And so, only IL-8 levels are being reported herein. The analysis was exploratory and no statistical analysis was performed.