Trial Outcomes & Findings for PTI-125 for Mild-to-moderate Alzheimer's Disease Patients (NCT NCT04079803)

NCT ID: NCT04079803

Last Updated: 2021-09-29

Results Overview

Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

64 participants

Primary outcome timeframe

Screening to Day 28

Results posted on

2021-09-29

Participant Flow

Participant milestones

Participant milestones
Measure	Simufilam (PTI-125), 100 mg Tablets Cohort Subjects administered simufilam 100 mg oral tablets twice daily (BID)	Simufilam (PTI-125), 50 mg Tablets Cohort Subjects administered simufilam 50 mg oral tablets twice daily (BID)	Placebo Cohort Subjects administered placebo oral tablets twice daily (BID)
Overall Study STARTED	21	21	22
Overall Study COMPLETED	21	20	22
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Simufilam (PTI-125), 100 mg Tablets Cohort Subjects administered simufilam 100 mg oral tablets twice daily (BID)	Simufilam (PTI-125), 50 mg Tablets Cohort Subjects administered simufilam 50 mg oral tablets twice daily (BID)	Placebo Cohort Subjects administered placebo oral tablets twice daily (BID)
Overall Study Withdrawal by Subject	0	1	0

Baseline Characteristics

The least impaired patients (11 or fewer errors, representing a ceiling effect) and patients with 54 or more errors (very poor performance suggesting not understanding the task) were removed from the analysis. Also removed were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Screening to Day 28

Population: As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample. This primary analysis includes one 50 mg subject who showed no detectable simufilam in plasma at return visits (their exclusion was not prespecified in the Statistical Analysis Plan).

Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid levels of Amyloid beta42

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=21 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=19 Participants simufilam 50 mg tablets BID for 28 days
Change From Baseline in CSF Abeta42	4.8 pg/mL Standard Deviation 30.9	12.5 pg/mL Standard Deviation 11.9	16.2 pg/mL Standard Deviation 21.1

PRIMARY outcome

Timeframe: Screening to Day 28

Change from Baseline (screening sample) to Day 28 in cerebrospinal fluid total tau.

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=21 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=19 Participants simufilam 50 mg tablets BID for 28 days
Change From Baseline in CSF Total Tau.	-3.2 pg/mL Standard Deviation 14.8	-18.7 pg/mL Standard Deviation 10.4	-14.6 pg/mL Standard Deviation 9.6

PRIMARY outcome

Timeframe: Screening to Day 28

Change from Baseline (screening) to Day 28 in cerebrospinal fluid P-tau181

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=21 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=19 Participants simufilam 50 mg tablets BID for 28 days
Change From Baseline in CSF P-tau181	-0.63 pg/mL Standard Deviation 1.8	-3.1 pg/mL Standard Deviation 1.7	-2.4 pg/mL Standard Deviation 1.6

PRIMARY outcome

Timeframe: Screening to Day 28

Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurogranin

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=21 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=19 Participants simufilam 50 mg tablets BID for 28 days
Change From Baseline in CSF Neurogranin	-50.5 pg/mL Standard Deviation 434	-648 pg/mL Standard Deviation 491	-527 pg/mL Standard Deviation 361

PRIMARY outcome

Timeframe: Screening to Day 28

Change from Baseline (screening) to Day 28 in cerebrospinal fluid neurofilament light chain

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=21 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=19 Participants simufilam 50 mg tablets BID for 28 days
Change From Baseline in CSF Neurofilament Light Chain	-10.0 pg/mL Standard Deviation 45	-76.3 pg/mL Standard Deviation 50.6	-49.7 pg/mL Standard Deviation 35.5

PRIMARY outcome

Timeframe: Screening to Day 28

Change from Baseline (screening) in cerebrospinal fluid YKL-40

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=21 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=19 Participants simufilam 50 mg tablets BID for 28 days
Change From Baseline in CSF YKL-40	-0.96 pg/mL Standard Deviation 24.2	-22.3 pg/mL Standard Deviation 11.7	-20.4 pg/mL Standard Deviation 17.4

SECONDARY outcome

Timeframe: Day 1 to Day 28

Population: The least impaired patients (11 or fewer errors, representing a ceiling effect) and patients with 54 or more errors (very poor performance suggesting not understanding the task) were removed from the analysis. Also removed were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.

Cognitive test assessing episodic memory. Boxes are displayed on the screen and are "opened" in a randomized order. One or more of them contains a pattern. The patterns are then displayed in the middle of the screen, one at a time and the participant must select the box in which the pattern was originally located. If the participant makes an error, the boxes are opened in sequence again to remind the participant of the locations of the patterns. The number of boxes increases progressively to a total of 8.

Outcome measures

Outcome measures
Measure	Placebo Cohort n=14 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=13 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=10 Participants simufilam 50 mg tablets BID for 28 days
Paired Associates Learning Test	-1.5 Change from Day 1 in total errors Standard Deviation 8.5	-4.5 Change from Day 1 in total errors Standard Deviation 17.7	-5.7 Change from Day 1 in total errors Standard Deviation 13.6

SECONDARY outcome

Timeframe: Day 1 to Day 28

Population: Removed from analysis were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.

Cognitive assessment of spatial working memory: A number of colored squares (boxes) are shown on the screen. By selecting the boxes and using a process of elimination, the subject should find one yellow 'token' in each of a number of boxes and use them to fill up an empty column on the right-hand side of the screen. The number of boxes is gradually increased to a total of 8 for the subjects to search. The colors and positions of the boxes are changed from trial to trial to discourage stereotyped search strategies.

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=18 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=17 Participants simufilam 50 mg tablets BID for 28 days
Spatial Working Memory Test	-0.41 Change from Day 1 in total errors Standard Deviation 7.54	-2.31 Change from Day 1 in total errors Standard Deviation 7.45	-3.35 Change from Day 1 in total errors Standard Deviation 4.86

SECONDARY outcome

Timeframe: Screening to Day 28

Population: Three subjects who had no detectable simufilam in plasma at return visits were removed from analyses (two in the 100 mg arm and one in the 50 mg arm). As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. One additional subject in the 50 mg arm was missing a Day 28 CSF sample.

Change from Baseline (screening sample) to Day 28 in secondary CSF biomarkers of neuroinflammation and blood-brain barrier integrity

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=19 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=18 Participants simufilam 50 mg tablets BID for 28 days
CSF IL-6, sTREM2, HMGB1, Albumin, IgG CSF sTREM2	-77.3 pg/mL; optical density for albumin & IgG Standard Deviation 510	-426 pg/mL; optical density for albumin & IgG Standard Deviation 274	-424 pg/mL; optical density for albumin & IgG Standard Deviation 386
CSF IL-6, sTREM2, HMGB1, Albumin, IgG CSF IL-6	-1.1 pg/mL; optical density for albumin & IgG Standard Deviation 2.0	-3.7 pg/mL; optical density for albumin & IgG Standard Deviation 1.8	-3.3 pg/mL; optical density for albumin & IgG Standard Deviation 1.9
CSF IL-6, sTREM2, HMGB1, Albumin, IgG CSF HMGB1	19.4 pg/mL; optical density for albumin & IgG Standard Deviation 172.3	-143 pg/mL; optical density for albumin & IgG Standard Deviation 51.3	-152 pg/mL; optical density for albumin & IgG Standard Deviation 50.1
CSF IL-6, sTREM2, HMGB1, Albumin, IgG CSF albumin	-240 pg/mL; optical density for albumin & IgG Standard Deviation 1620	-2292 pg/mL; optical density for albumin & IgG Standard Deviation 1760	-1245 pg/mL; optical density for albumin & IgG Standard Deviation 1735
CSF IL-6, sTREM2, HMGB1, Albumin, IgG CSF IgG	-574.8 pg/mL; optical density for albumin & IgG Standard Deviation 2518	-2350 pg/mL; optical density for albumin & IgG Standard Deviation 2517	-2444 pg/mL; optical density for albumin & IgG Standard Deviation 2097

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 28

Population: Three subjects who had no detectable simufilam in plasma at any return visit were removed from analyses (two in the 100 mg arm and one in the 50 mg arm). As noted in the Participant Flow, one subject in the 50 mg arm did not complete the study. Two additional subjects in the 50 mg arm were missing Day 1 blood samples.

FLNA linkages to these two receptors were assessed by densitometric quantitation of immunoblot bands of each receptor (detected by a specific antibody) in anti-FLNA precipitates. The measure is noted as a ratio to total FLNA.

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=19 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=17 Participants simufilam 50 mg tablets BID for 28 days
Target Engagement Assays: Change From Baseline in Filamin A (FLNA) Linkages to alpha7 Nicotinic Acetylcholine Receptor (alpha7nAChR) and Toll-like Receptor 4 (TLR4) in Subject Lymphocytes FLNA - alpha7nAChR linkage	-0.07 ratio to total FLNA Standard Deviation 0.19	-0.24 ratio to total FLNA Standard Deviation 0.16	-0.23 ratio to total FLNA Standard Deviation 0.13
Target Engagement Assays: Change From Baseline in Filamin A (FLNA) Linkages to alpha7 Nicotinic Acetylcholine Receptor (alpha7nAChR) and Toll-like Receptor 4 (TLR4) in Subject Lymphocytes FLNA - TLR4 linkage	-0.05 ratio to total FLNA Standard Deviation 0.18	-0.19 ratio to total FLNA Standard Deviation 0.14	-0.19 ratio to total FLNA Standard Deviation 0.11

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 28

Population: For plasma p-tau181 only: 4 subjects (1 in placebo, 2 in 50 mg and 1 in 100 mg arms) were removed because Coefficients of Variation (CVs) between duplicate measurements for either Day 1 or Day 28 samples were \>15% on repeat assay (both Day 1 \& Day 28 for a subject were repeated if CVs of either Day 1 or Day 28 were \>11%). Two outliers were removed (1 in placebo \[1.2 to 4.8 pg/ml\] and 1 in 100 mg \[2.1 to 5.1 pg/ml\] arms) for increases \>150% \& \> 2.5 pg/mL. Missing Day 1 blood samples: 2 in 50 mg.

Percent change in plasma P-tau181

Outcome measures

Outcome measures
Measure	Placebo Cohort n=20 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=17 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=15 Participants simufilam 50 mg tablets BID for 28 days
Plasma P-tau181	20.7 Percent change Standard Deviation 49	-16.5 Percent change Standard Deviation 29	-15.1 Percent change Standard Deviation 36

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 to Day 28

Population: One subject in the 50 mg arm and two subjects in the 100 mg arm were omitted because these subjects showed no detectable plasma simufilam at any return visit. Two additional subjects in the 50 mg group were missing baseline plasma samples.

SavaDx is a novel plasma biomarker

Outcome measures

Outcome measures
Measure	Placebo Cohort n=22 Participants Placebo tablets BID for 28 days	Simufilam (PTI-125), 100 mg Tablets Cohort n=19 Participants simufilam 100 mg tablets BID for 28 days	Simufilam (PTI-125), 50 mg Tablets Cohort n=17 Participants simufilam 50 mg tablets BID for 28 days
Percent Change From Baseline in SavaDx, a Novel Plasma Biomarker	-3.2 Percent change Standard Deviation 62	-47.8 Percent change Standard Deviation 19	-44.1 Percent change Standard Deviation 35

Adverse Events

Placebo Cohort

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Simufilam (PTI-125), 100 mg Tablets Cohort

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Simufilam (PTI-125), 50 mg Tablets Cohort

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Placebo Cohort n=22 participants at risk Subjects administered placebo tablets twice daily (BID) for 28 days.	Simufilam (PTI-125), 100 mg Tablets Cohort n=21 participants at risk Subjects administered simufilam 100 mg tablets twice daily (BID) for 28 days.	Simufilam (PTI-125), 50 mg Tablets Cohort n=21 participants at risk Subjects administered simufilam 50 mg tablets twice daily (BID) for 28 days.
Nervous system disorders Headache	13.6% 3/22 • Number of events 3 • 28 days	9.5% 2/21 • Number of events 2 • 28 days	4.8% 1/21 • Number of events 1 • 28 days
Metabolism and nutrition disorders Fatigue	9.1% 2/22 • Number of events 2 • 28 days	0.00% 0/21 • 28 days	4.8% 1/21 • Number of events 1 • 28 days
Gastrointestinal disorders Nausea	9.1% 2/22 • Number of events 2 • 28 days	4.8% 1/21 • Number of events 1 • 28 days	0.00% 0/21 • 28 days
General disorders Any adverse event	54.5% 12/22 • Number of events 20 • 28 days	42.9% 9/21 • Number of events 15 • 28 days	19.0% 4/21 • Number of events 9 • 28 days

Additional Information

Nadav Friedmann, PhD, MD, Chief Medical Officer

Cassava Sciences, Inc.

Phone: 512-501-1900

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Placebo Cohort n=22 Participants Subjects administered matching placebo tablets twice daily for 28 days.	Simufilam (PTI-125), 100 mg Tablets Cohort n=21 Participants Subjects administered 100 mg simufilam tablets twice daily for 28 days.	Simufilam (PTI-125), 50 mg Tablets Cohort n=21 Participants Subjects administered 50 mg simufilam tablets twice daily for 28 days.	Total n=64 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=22 Participants	0 Participants n=21 Participants	0 Participants n=21 Participants	0 Participants n=64 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=22 Participants	9 Participants n=21 Participants	6 Participants n=21 Participants	19 Participants n=64 Participants
Age, Categorical >=65 years	18 Participants n=22 Participants	12 Participants n=21 Participants	15 Participants n=21 Participants	45 Participants n=64 Participants
Age, Continuous	71.3 years STANDARD_DEVIATION 6.68 • n=22 Participants	69.3 years STANDARD_DEVIATION 5.47 • n=21 Participants	67.1 years STANDARD_DEVIATION 8.76 • n=21 Participants	69.2 years STANDARD_DEVIATION 6.97 • n=64 Participants
Sex: Female, Male Female	11 Participants n=22 Participants	12 Participants n=21 Participants	12 Participants n=21 Participants	35 Participants n=64 Participants
Sex: Female, Male Male	11 Participants n=22 Participants	9 Participants n=21 Participants	9 Participants n=21 Participants	29 Participants n=64 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=22 Participants	11 Participants n=21 Participants	11 Participants n=21 Participants	31 Participants n=64 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=22 Participants	10 Participants n=21 Participants	10 Participants n=21 Participants	33 Participants n=64 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=22 Participants	0 Participants n=21 Participants	0 Participants n=21 Participants	0 Participants n=64 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=22 Participants	0 Participants n=21 Participants	0 Participants n=21 Participants	0 Participants n=64 Participants
Race (NIH/OMB) Asian	1 Participants n=22 Participants	0 Participants n=21 Participants	0 Participants n=21 Participants	1 Participants n=64 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=22 Participants	0 Participants n=21 Participants	0 Participants n=21 Participants	0 Participants n=64 Participants
Race (NIH/OMB) Black or African American	2 Participants n=22 Participants	2 Participants n=21 Participants	4 Participants n=21 Participants	8 Participants n=64 Participants
Race (NIH/OMB) White	19 Participants n=22 Participants	19 Participants n=21 Participants	17 Participants n=21 Participants	55 Participants n=64 Participants
Race (NIH/OMB) More than one race	0 Participants n=22 Participants	0 Participants n=21 Participants	0 Participants n=21 Participants	0 Participants n=64 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=22 Participants	0 Participants n=21 Participants	0 Participants n=21 Participants	0 Participants n=64 Participants
CSF total tau/Aβ42 ratio	1.20 ratio STANDARD_DEVIATION 0.55 • n=22 Participants	1.08 ratio STANDARD_DEVIATION 0.50 • n=21 Participants	1.17 ratio STANDARD_DEVIATION 0.58 • n=21 Participants	1.15 ratio STANDARD_DEVIATION 0.54 • n=64 Participants
Mini-Mental State Exam (MMSE)	23.1 units on a scale STANDARD_DEVIATION 2.78 • n=22 Participants	23.0 units on a scale STANDARD_DEVIATION 2.66 • n=21 Participants	22.7 units on a scale STANDARD_DEVIATION 2.67 • n=21 Participants	22.9 units on a scale STANDARD_DEVIATION 2.70 • n=64 Participants
Taking cholinesterase inhibitor or memantine	8 Participants n=22 Participants	7 Participants n=21 Participants	5 Participants n=21 Participants	20 Participants n=64 Participants
Heterozygous APOE4	12 Participants n=22 Participants	14 Participants n=21 Participants	9 Participants n=21 Participants	35 Participants n=64 Participants
Homozygous APOE4	1 Participants n=22 Participants	1 Participants n=21 Participants	3 Participants n=21 Participants	5 Participants n=64 Participants
Paired Associates Learning total errors	35.5 errors STANDARD_DEVIATION 19.65 • n=14 Participants • The least impaired patients (11 or fewer errors, representing a ceiling effect) and patients with 54 or more errors (very poor performance suggesting not understanding the task) were removed from the analysis. Also removed were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.	31.0 errors STANDARD_DEVIATION 20.74 • n=13 Participants • The least impaired patients (11 or fewer errors, representing a ceiling effect) and patients with 54 or more errors (very poor performance suggesting not understanding the task) were removed from the analysis. Also removed were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.	36.1 errors STANDARD_DEVIATION 18.76 • n=10 Participants • The least impaired patients (11 or fewer errors, representing a ceiling effect) and patients with 54 or more errors (very poor performance suggesting not understanding the task) were removed from the analysis. Also removed were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.	34.2 errors STANDARD_DEVIATION 19.7 • n=37 Participants • The least impaired patients (11 or fewer errors, representing a ceiling effect) and patients with 54 or more errors (very poor performance suggesting not understanding the task) were removed from the analysis. Also removed were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes.
Spatial Working Memory total errors	19.0 errors STANDARD_DEVIATION 7.49 • n=22 Participants • Removed from analysis were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes	22.1 errors STANDARD_DEVIATION 5.88 • n=18 Participants • Removed from analysis were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes	22.3 errors STANDARD_DEVIATION 6.64 • n=17 Participants • Removed from analysis were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes	21.1 errors STANDARD_DEVIATION 6.67 • n=57 Participants • Removed from analysis were the 3 patients with no detectable drug in plasma, 2 patients with ≥25% non-compliance by pill counts, one patient with no baseline test and one who did not understand instructions per rater notes
CSF Aβ42	125 pg/mL STANDARD_DEVIATION 152 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	117 pg/mL STANDARD_DEVIATION 51.4 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	108 pg/mL STANDARD_DEVIATION 54.8 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	111 pg/mL STANDARD_DEVIATION 86.1 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF total tau	104 pg/mL STANDARD_DEVIATION 32 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	106 pg/mL STANDARD_DEVIATION 27.9 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	101 pg/mL STANDARD_DEVIATION 17.6 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	103.7 pg/mL STANDARD_DEVIATION 25.8 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF P-tau181	28.5 pg/mL STANDARD_DEVIATION 0.73 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	29.7 pg/mL STANDARD_DEVIATION 1.5 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	29.0 pg/mL STANDARD_DEVIATION 1.0 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	29.1 pg/mL STANDARD_DEVIATION 1.3 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF neurogranin	1200 pg/mL STANDARD_DEVIATION 365 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	1551 pg/mL STANDARD_DEVIATION 751 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	1352 pg/mL STANDARD_DEVIATION 614 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	1368 pg/mL STANDARD_DEVIATION 577 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF Neurofilament Light Chain	161 pg/mL STANDARD_DEVIATION 42.8 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	219 pg/mL STANDARD_DEVIATION 95.3 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	181 pg/mL STANDARD_DEVIATION 64.4 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	187 pg/mL STANDARD_DEVIATION 67.5 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF YKL-40	206 pg/mL STANDARD_DEVIATION 29.5 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	203 pg/mL STANDARD_DEVIATION 22.7 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	194 pg/mL STANDARD_DEVIATION 26.0 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	201 pg/mL STANDARD_DEVIATION 26.1 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF IL-6	32.5 pg/mL STANDARD_DEVIATION 1.2 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	33.6 pg/mL STANDARD_DEVIATION 1.8 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	33.6 pg/mL STANDARD_DEVIATION 1.7 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	33.2 pg/mL STANDARD_DEVIATION 1.6 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF sTREM2	878 pg/mL STANDARD_DEVIATION 435 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	861 pg/mL STANDARD_DEVIATION 421 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	882 pg/mL STANDARD_DEVIATION 476 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	874 pg/mL STANDARD_DEVIATION 444 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF HMGB1	424 pg/mL STANDARD_DEVIATION 48.0 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	446 pg/mL STANDARD_DEVIATION 67.3 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	454 pg/mL STANDARD_DEVIATION 70.6 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	441 pg/mL STANDARD_DEVIATION 62.0 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF/plasma albumin ratio	0.24 ratio STANDARD_DEVIATION 0.03 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.25 ratio STANDARD_DEVIATION 0.08 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.25 ratio STANDARD_DEVIATION 0.05 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.25 ratio STANDARD_DEVIATION 0.05 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
CSF/plasma IgG ratio	0.200 ratio STANDARD_DEVIATION 0.07 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.217 ratio STANDARD_DEVIATION 0.11 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.227 ratio STANDARD_DEVIATION 0.07 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.215 ratio STANDARD_DEVIATION 0.08 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
Lymphocyte filamin A - α7nAChR, Ratio to total filamin A	0.59 ratio STANDARD_DEVIATION 0.10 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.69 ratio STANDARD_DEVIATION 0.11 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.66 ratio STANDARD_DEVIATION 0.12 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.65 ratio STANDARD_DEVIATION 0.11 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.
Lymphocyte filamin A - TLR4, Ratio to total filamin A	0.55 ratio STANDARD_DEVIATION 0.10 • n=22 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.60 ratio STANDARD_DEVIATION 0.07 • n=19 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.58 ratio STANDARD_DEVIATION 0.11 • n=18 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.	0.58 ratio STANDARD_DEVIATION 0.09 • n=59 Participants • One subject is missing a CSF sample. Three others had no detectable simufilam in plasma and were excluded from analyses.