Study of the Efficacy and Safety of Various Anti-inflammatory Agents in Participants With Mild Cognitive Impairment or Mild Alzheimer's Disease

Total Neuropsychological Test Battery memory composite score is a "memory function" score composed of the NTB RAVLT immediate and delayed scores.

For each component a raw score was converted to z-score that indicates the number of standard deviations away from the mean. Total Z-score was derived by averaging the two resulting z-scores. A change from baseline was calculated as post-baseline z-score minus pre-treatment z-score. A zero Z-score means no cognitive change, a negative value indicates decline, and a positive value means improvement.

The total Neuropsychological Test Battery executive function composite score is an "executive function" score composed of the NTB Wechsler Memory Scale Digit Span, COWAT, and CFT.

For each component a raw score was converted to z-score that indicates the number of standard deviations away from the mean. Total Z-score was derived by averaging the two resulting z-scores. A change from baseline was calculated as post-baseline z-score minus pre-treatment z-score. A zero Z-score means no cognitive change, a negative value indicates decline, and a positive value means improvement.

The DSST is an attention-demanding component of the Wechsler Adult Intelligence Scale-IV.

The DSST score is the number of digits coded correctly in a fixed amount of time. The DSST has a minimum of "0" correct responses and does not have a maximum; a higher number on the DSST represents better performance

The test was administered using CANTAB web based testing

Neuropsychiatric Inventory (NPI) total score is globally recognized and the most frequently used assessment of neuropsychiatric symptoms in AD trials. NPI covers twelve neuropsychiatric domains. For each domain there are four scores, frequency (rated 1-4), severity (rated 1-3), domain total score (frequency x severity) and caregiver distress score (rated 0-5).

The NPI total score was calculated by adding 12 domain total scores together, and ranges from 0 to 144, with higher values indicating greater severity.

Neuropsychiatric Inventory (NPI) total score is globally recognized and the most frequently used assessment of neuropsychiatric symptoms in AD trials. NPI covers twelve neuropsychiatric domains. For each domain there are four scores, frequency (rated 1-4), severity (rated 1-3), domain total score (frequency x severity) and caregiver distress score (rated 0-5).

The caregiver distress score (NPI-D) was calculated by adding together the scores of the 12 individual NPI distress questions, and ranges from 0 to 60, with higher values indicating greater severity.

Neuropsychiatric Inventory (NPI) total score is globally recognized and the most frequently used assessment of neuropsychiatric symptoms in AD trials. NPI covers twelve neuropsychiatric domains. For each domain there are four scores, frequency (rated 1-4), severity (rated 1-3), domain total score (frequency x severity) and caregiver distress score (rated 0-5).

The eNeuropsychiatric at-home assessment was calculated the same way as the in-clinic NPI by adding the12 domain total scores together. The eNeuropsychiatric at-home assessments were completed more frequently than the single time-point in-clinic NPI assessment and the scores averaged. It ranges from 0 to 144, with higher values indicating greater severity.

Everyday Cognition (ECog) scale measures cognitively-relevant everyday abilities and is comprised of 39 items covering six cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. Each item is scored on a 4 point scale (1=better or no change compared to 10 years earlier, 2=questionable/occasionally worse, 3=consistently a little worse, 4=consistently much worse). An "I don't know" response is also included, in that case the item is not included in the calculation.

The total ECog score is calculated as the sum of all 39 items, and ranges from 0 to 156. Lower total ECog scores indicate better performance.

Spatial Working Memory (SWM) is a test of the subject's ability to retain spatial information and to manipulate remembered items in working memory. A trial begins with several colored squares (boxes) being shown on the screen. The overall aim is that the subject should find a blue 'token' in each of the boxes and use them to fill up an empty column. The subject must touch each box in turn until one opens with a blue 'token' inside (a search). Returning to an empty box already sampled on this search is an error.

SWM between errors is the number of times the subject incorrectly revisits a box in which a token has previously been found. It starts at 0 without a maximum limit with higher scores indicating a worse outcome.

Spatial Working Memory (SWM) is a test of the subject's ability to retain spatial information and to manipulate remembered items in working memory. A trial begins with several colored squares (boxes) being shown on the screen. The overall aim is that the subject should find a blue 'token' in each of the boxes and use them to fill up an empty column. The subject must touch each box in turn until one opens with a blue 'token' inside (a search). Returning to an empty box already sampled on this search is an error.

SWM Strategy is the number of times a subject begins a new search pattern from the same box they started with previously. If they always begin a search from the same starting point, we infer that the subject is employing a planned strategy for finding the tokens. SMW strategy ranges from 3 to 26, a low score indicates high strategy use, they always begin the search from the same box, and a high score indicates that they are beginning their searches from many different boxes.

Match to Sample Visual Search (MTS) assesses attention and visual searching, with a speed accuracy trade-off. The participant is shown a complex visual pattern in the middle of the screen. After a brief delay, a varying number of similar patterns are shown in a circle of boxes around the edge of the screen. Only one of these patterns matches the pattern in the center of the screen, and the participant must indicate which it is by selecting it.

MTS proportional slowing 8-2 patterns is the difference in mean time between presentation of the response stimulus options and the subject selecting the correct box on their first attempt on the 8 pattern assessment trials compared to the 2 pattern assessment trials. It starts at 0 without a maximum limit, and with higher scores indicating a worse outcome.

Pair associated learning (PAL): tests participants' visual memory/new learning using patterns randomly displayed in boxes on a screen. Participants are to touch the box where patterns first appeared.

PAL first attempt memory score is the number of times a subject choses the correct box on their first attempt when recalling the pattern locations. Ranges from 0 to 20 with higher score indicates a better outcome.

Positron-Emission Tomography-Translocator Protein 18kDa-microglia activation (PET TSPO) is considered a marker of central inflammation (a marker for activated microglia and astrocytes) and the signal strength has been shown to correlate with worsening clinical severity in participants with MCI or AD, measures of cognition and various clinical scores. Relative % change from baseline in volume of distribution (Vt) of the radio tracer for TSPO after treatment.

Since only one participant completed day 85 PET TSPO, no data is reported here in order to protect and maintain participant privacy/confidentiality.

Serum pharmacokinetic pre-dose concentrations of CanakinumabConcentrations below the LLOQ were reported as "zero".

Serum and CSF samples were obtained and evaluated for total target concentrations (the sum of free and drug-bound target) as a pharmacodynamic (PD) marker for target engagement.

Number of participants with anti-agent antibodies in serum. Immunogenicity (IG) was assessed in serum of all participants treated with biotherapeutic drug.

Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram findings and other safety assessments were recorded as adverse events if the findings meet the defined criteria for adverse events.

AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5. For CTCAE, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE