Conditions: Mild to Moderate Alzheimer's Disease
Keywords: Alzheimer's Disease
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 153
Healthy volunteers: no

Brief summary:
This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's Disease (AD).

Detailed description:
This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's Disease (AD).

This Phase 2 study is designed to evaluate the safety of two doses of CT1812 administered once daily for 6 months in adults aged 50 to 85 who have been diagnosed with mild to moderate Alzheimer's disease. Randomized participants will receive 100 mg of CT1812, 300 mg of CT1812, or placebo once daily for 182 days. Exploratory endpoints that evaluate the effect of CT1812 on biomarkers are also included.

Arms:
arm 1: CT1812 at a dose of 100 mg arm 2: CT1812 at a dose of 300mg arm 3: Placebo

Interventions: intervention 1: CT1812 intervention 2: Placebo
Intervention descriptions: intervention 1: Active Study Drug intervention 2: Non-active study drug

Protocol document:
Prot_000.pdf: 
 
 
     Cognition Therapeutics, Inc. 
 
 
2500 Westchester Avenue Suite 220 
Purchase, NY 10577 
 
 
412-481-2210 
 
 
  
 Document: Redacted Protocol COG0201 
 
  
Official Title:  A 
Randomized, 
Double-Blind, 
Placebo-
Controlled, Parallel-Group, Phase 2 Study to Evaluate the 
Safety and Efficacy of CT1812 in Subjects With Mild to 
Moderate Alzheimer's Disease. 
  
ClinicalTrials.gov ID (NCT number): NCT03507790  
  
Protocol Date : Version 6.0_12 June 2023 
  
 

































































































































































































SAP_001.pdf: 
 
 
     Cognition Therapeutics, Inc. 
 
 
2500 Westchester Avenue Suite 220 
Purchase, NY 10577 
 
 
412-481-2210 
 
 
 
  
 Document: Redacted SAP COG0201 
 
  
Official Title:  A 
Randomized, 
Double-Blind, 
Placebo-
Controlled, Parallel-Group, Phase 2 Study to Evaluate the 
Safety and Efficacy of CT1812 in Subjects With Mild to 
Moderate Alzheimer's Disease. 
  
ClinicalTrials.gov ID (NCT number): NCT03507790  
  
Statistical Analysis Plan Date: 23May2024 
  
 


AD-ST-33.05  Effective date: 22-Jan-2018
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Page 1 of 37
   Statistical Analysis Plan
Sponsor
Cognition Therapeutics, Inc.
Protocol Title:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-
Group, Phase 2 Study to Evaluate the Safety and Efficacy of 
CT1812 in Participant
Disease
Protocol Number:
COG0201
Document Version:
Final 2.0
Document Date: 
23May2024
Approvals
Role
Signatures
Date (dd-Mmm-yyyy)
Biostatistician
Print Name: 
Sign Name:
Senior Reviewer
Print Name:
Sign Name:
Cognition 
Therapeutics, Inc.
Representative
Print Name:
Sign Name:


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 2 of 37
Document History
Final V1.0
18-Dec-2019 Initial version
Final V2.0
Updated throughout to align with V6.0 of the protocol.
Removal of Per-Protocol Population, addition of Completers Population and PK 
Population throughout.
Section 2.1.3 (Exploratory Objectives) was updated from "To identify and assess 
metabolites of CT1812 in plasma" to "To characterize the PK profile of CT1812 
in plasma". 
Section 2.2.3 (Pharmacokinetic/Pharmacodynamic Endpoints) was updated to
remove one of the PK endpoints "Plasma CT1812 metabolites".
Section 3.1 (Overall Design) was updated to add the definition of Part A, Part B 
and Part C.
Section 3.2 (Sample Size and Power) was updated to include 48 active-dosed 
participants in sample size.
Section 3.7 (SOE) was updated to align with Protocol Amendment 6.0.
Section 5 (Analysis Populations) was updated to include definition for All 
Subjects population, Completers Population and PK Population.
Section 6 (General Issues for Statistical Analysis) was updated to include a 
section on the subgroups of interest. The previously defined subgroup based on 
CT1812 CSF concentration was removed. A statement was added to document 
that tables and figures will present data for each individual CT1812 dose group as 
well as a combined CT1812 dose group (100 mg + 300 mg together).
Section 6.1.1 (Baseline) was updated to include the day of first dose in the 
definition of Baseline.
Section 6.1.3 (Multiple Comparisons) was updated to include text that had 
previously been included in Section 8.3 (ADAS-Cog 14).
Section 6.1.4 (Handling of Dropouts or Missing Data) was updated to clarify that 
only missing data for endpoints assessed at post baseline timepoints may be 
imputed using LOCF.
Section 6.1.8 (Derived Variables) was updated to remove derivation of MMSE 
Total Score, added derivation of Modified Hachinski total score, ADCS-ADL 
total score, Number Cancellation total score and ADAS 13 total score. And 
updated definition of TEAE to include AEs with an onset date/time on the first 
dose of study drug.
Section 6.1.9 (Data Adjustments/Handling/Conventions) was updated to include


Statistical Analysis Plan, 
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Protocol Number COG0201
PCN Number COGN187880
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Page 3 of 37
imputation for missing AE dates.
Section 6.1.10 was added to define subgroups.
Section 7.1 (Disposition of Participants and Withdrawals) was updated to remove 
summary of treatment discontinuation.
Section 7.3 (Demographics and Other Baseline Characteristics) was updated to 
inlcude ApoE4 Status, ApoE Genotype, and Mini Mental State Exam (MMSE) 
Total Score in baseline characteristics summary. Also added clarification that 
demographic table for mITT population will be produced when mITT population 
is different from the Safety population.
Section 8 (Efficacy Analysis) was updated to include details on which efficacy 
endpoints would be summarized using the Completers Population and the types 
of figures to be produced.
Section 8.8 (Biomarker changes) was significantly updated to reflect the planned 
analyses for the final study analysis. Added rules for subgroup analyses. Added 
figures to be produced at final analysis.
Section 9 (Safety and Tolerability Analysis) was updated throughout to include 
the visits at which by-visit summaries of safety data would be summarized
(Section 9.3 Vital Signs, Section 9.4 ECGs and Section 9.5 PE).
Section 9.2 (Clinical Laboratory Evaluations) was updated to include clarification 
to data sources from both local lab and central lab.
Section 9.6 (C-SSRS) was updated to clarify the listing of suicidality data will 
only include data for participants with at least one occurrence of suicidal ideation 
or behavior during treatment.
Section 9.7 (Prior and Concomitant Medications) was updated to include the
definition of prior medications.
Section 10 (Changes from Planned Analysis) was updated to include the All 
Subjects, mITT, Completers, and PK Populations and to document the removal of 
the Per-Protocol Population. Also added changes from protocol: composite z-
score scales are added as one of the efficacy endpoints.
Section 11.1 (PK and PD Analysis) was updated to remove the reference to 
exploratory biomarkers, as this information is already contained in Section 8.8 
(Biomarker changes).
Section 12 (References) was updated to remove references 4 and 5.


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 4 of 37
Table of Contents
Approvals........................................................................................................................................ 1
Document History........................................................................................................................... 2
Table of Contents............................................................................................................................ 4
List of Tables .................................................................................Error! Bookmark not defined.
List of Figures................................................................................Error! Bookmark not defined.
1.
Overview............................................................................................................................. 6
2.
Study Objectives and Endpoints......................................................................................... 6
2.1.
Study Objectives ........................................................................................................... 6
2.1.1. Primary Objective......................................................................................................... 6
2.1.2. Secondary Objective..................................................................................................... 6
2.1.3. Exploratory Objectives ................................................................................................. 6
2.2.
Study Endpoints............................................................................................................ 7
2.2.1. Safety Endpoints........................................................................................................... 7
2.2.2. Efficacy Endpoints........................................................................................................ 7
2.2.3. Pharmacokinetic/Pharmacodynamic Endpoints............................................................ 7
3.
Overall Study Design and Plan........................................................................................... 8
3.1.
Overall Design .............................................................................................................. 8
3.2.
Sample Size and Power................................................................................................. 9
3.3.
Study Population........................................................................................................... 9
3.4.
Treatments Administered.............................................................................................. 9
3.5.
Method of Assigning Participants to Treatment Groups .............................................. 9
3.6.
Blinding and Unblinding............................................................................................... 9
3.7.
Schedule of Events...................................................................................................... 10
4.
Statistical Analysis and Reporting.................................................................................... 15
4.1.
Introduction................................................................................................................. 15
4.2.
Interim Analysis and Data Monitoring ....................................................................... 15
5.
Analysis Populations......................................................................................................... 16
6.
General Issues for Statistical Analysis.............................................................................. 16
6.1.
Statistical Definitions and Algorithms........................................................................ 16
6.1.1. Baseline....................................................................................................................... 16
6.1.2. Adjustments for Covariates......................................................................................... 17
6.1.3. Multiple Comparisons................................................................................................. 17
6.1.4. Handling of Dropouts or Missing Data....................................................................... 17
6.1.5. Outlier Values and Values below the Limit of Quantitation ...................................... 18
6.1.6. Analysis Visit Windows ............................................................................................. 18
6.1.7. Pooling of Sites........................................................................................................... 18


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
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6.1.8. Derived Variables ....................................................................................................... 18
6.1.9. Data Adjustments/Handling/Conventions .................................................................. 21
6.1.10. Subgroups ................................................................................................................... 23
7.
Study Participants and Demographics .............................................................................. 24
7.1.
Disposition of Participants and Withdrawals.............................................................. 24
7.2.
Protocol Violations and Deviations ............................................................................ 24
7.3.
Demographics and Other Baseline Characteristics..................................................... 24
7.4.
Exposure and Compliance .......................................................................................... 24
8.
Efficacy Analysis.............................................................................................................. 25
8.1.
Composite z-scores..................................................................................................... 25
8.2.
Mini Mental State Exam (MMSE).............................................................................. 26
8.3.
-Cognition Subscale (ADAS-Cog 14).......... 26
8.4.
Neuropsychological Test Battery (NTB).................................................................... 27
8.5.
ADCS-Clinical Global Impression of Change (ADCS-CGIC) .................................. 27
8.6.
ADCS-Activities of Daily Living (ADCS-ADL) ....................................................... 28
8.7.
Cognitive Composite Score and its Components........................................................ 29
8.8.
Biomarker Changes..................................................................................................... 29
8.9.
Other Exploratory Efficacy Analyses ......................................................................... 31
9.
Safety and Tolerability Analysis....................................................................................... 31
9.1.
Adverse Events ........................................................................................................... 31
9.1.1. Adverse Events Leading to Withdrawal ..................................................................... 32
9.1.2. Deaths and Serious Adverse Events ........................................................................... 32
9.2.
Clinical Laboratory Evaluations ................................................................................. 32
9.2.1. Protocol-Required Safety Laboratory Tests................................................................ 32
9.3.
Vital Signs................................................................................................................... 33
9.4.
Electrocardiograms ..................................................................................................... 33
9.5.
Physical Examination.................................................................................................. 33
9.6.
Columbia Suicide Severity Rating Scale (C-SSRS)................................................... 34
9.7.
Prior and Concomitant Medications ........................................................................... 35
10.
Changes from Planned Analysis ....................................................................................... 35
11.
Other Planned Analysis..................................................................................................... 36
11.1.
Pharmacokinetic and Pharmacodynamic Analysis ..................................................... 36
12.
References......................................................................................................................... 37


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 6 of 37
1.
Overview
This statistical analysis plan (SAP) describes the planned analysis and reporting for Cognition 
Therapeutics, Inc. protocol number COG0201 (A Randomized, Double-Blind, Placebo-
Controlled, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in 
Participant
6.0, dated 13-Jun-2023. 
Reference materials for this statistical plan include the protocol and the accompanying sample 
data collection documents. Operational aspects related to collection and timing of planned 
clinical assessments are not repeated in this SAP unless relevant to the planned analysis.
The structure and content of this SAP provides sufficient detail to meet the requirements 
identified by the Food and Drug Administration (FDA), European Medicines Agency (EMA), 
and International Conference on Harmonization (ICH) of Technical Requirements for 
Registration of Pharmaceuticals for Human Use: Guidance on Statistical Principles in Clinical 
Trials1. All work planned and reported for this SAP will follow internationally accepted 
guidelines, published by the American Statistical Association2 and the Royal Statistical Society3
for statistical practice.
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. Also, post-hoc exploratory analyses not 
necessarily identified in this SAP may be performed to further examine study data. Any post-hoc 
or unplanned, exploratory analysis performed will be clearly identified as such in the final CSR.
The statistical plan described hereafter is an a priori plan. It will be submitted to file prior to any 
unblinded inferential or descriptive analysis of data pertaining to Cognition Therapeutics, Inc.
study COG0201.
2.
Study Objectives and Endpoints
2.1.
Study Objectives
2.1.1. Primary Objective
The primary objective of the study is to:
To assess the safety and tolerability of CT1812 in participants with mild to moderate 
2.1.2. Secondary Objective
The secondary objective of the study is to:
To assess target engagement and identify pharmacodynamic effects of CT1812 on 
cerebrospinal fluid (CSF) biomarkers.
2.1.3. Exploratory Objectives
The exploratory objectives of the study are:
To characterize the PK profile of CT1812 in plasma.


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
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To assess the efficacy of CT1812 as a treatment for mild to mode
2.2.
Study Endpoints
2.2.1. Safety Endpoints
The safety endpoints of this study include the following:
The incidence and severity of adverse events (AEs).
The change in usage of concomitant medications.
Changes in vital signs.
Changes in physical exam findings.
Changes in electrocardiogram findings.
Changes in clinical laboratory testing (serum chemistry, hematology, urinalysis).
Changes in the Columbia Suicide Severity Rating Scale (C-SSRS).
2.2.2. Efficacy Endpoints
The efficacy endpoints of this study include:
Mini Mental State Exam (MMSE).
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11 and-ADAS-
Cog 13 (delayed recall and Number Cancellation added to ADAS-11 in the ADAS-13).
Neuropsychological Test Battery (NTB) including Trails A and B, Digit Span, and Letter 
and Category Fluency (COWAT and CFT). 
Alzheimer's Disease Cooperative Study (ADCS)-Clinical Global Impression of Change 
(CGIC).
ADCS-Activities of Daily Living (ADCS-ADL).
Composite z-score scales (Cognitive Composite score; Memory composite score; 
Attention composite score; Executive Function composite score).
2.2.3. Pharmacokinetic/Pharmacodynamic Endpoints
The pharmacokinetic (PK) endpoints of the study include the following: 
CT1812 CSF/plasma concentration ratio (end of study [EOS] only).
Changes in pre-dose CT1812 plasma concentrations.
The pharmacodynamic (PD) endpoints of the study include:


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 8 of 37
CSF- abeta, tau, phospho-tau, neurogranin, synaptotagmin, synaptosomal-associated 
exploratory target engagement biomarkers may also be evaluated.
3.
Overall Study Design and Plan
3.1.
Overall Design
This is a phase 2 multi-center, randomized, double-blind, placebo-controlled, parallel group 
26-week study of two doses of CT1812 in adults with mild to moderate AD.
Participants will be screened for eligibility by physical, laboratory, psychometric and neurologic 
examinations, and neuroimaging. Pre-
prior to randomization at Baseline/Day 1. After having met all inclusion criteria, and none of the 
exclusion criteria, participants will be randomized in a 1:1:1 ratio to one of three treatment arms 
(CT1812 at doses of 100 or 300 mg/day or placebo; up to n=48 per group). On clinic visit days, 
study drug will be taken in the clinic after all baseline procedures have been conducted. For days 
where there are no clinic visits, participants will ingest study drug each morning at home. 
Participants and their caregivers/study partner will return to the clinic for repeat 
psychometric/neurologic testing, safety procedures, and PK and PD sample collection at the 
intervals described below.
Participants will be enrolled in three parts of the study, referred to as Part A, Part B and Part C. 
Part A is defined as the first 24 participants enrolled in the trial, and an interim analysis will be 
conducted on these participants. Part B is defined as the 25th participant through the 62nd 
participant enrolled in the trial. Part C is defined as all participants enrolled after October 2021.
Participants in Part A and B will return to the clinic twice in the first week after baseline, weekly 
for 3 weeks, bimonthly until Day 70, then every 4 weeks until Day 182 (See Table 1). A follow-
up visit will occur approximately 30 days after the end of treatment.
Participants in Part C will return to the clinic on Day 7 and Day 14 after baseline, followed by 
twice-monthly visits until Day 70, then every four weeks until Day 182 (See Table 1). A follow 
up visit will occur approximately 30 days after the end of treatment. 
Participants who prematurely discontinue the study for any reason will be asked to attend a final 
safety and efficacy visit.
Following an adequate clinical and non-clinical safety review of data from this initial cohort of 
participants, the protocol may be amended to expand enrollment and treatment duration to 
12 months.
Participants who initially do not meet all enrollment criteria for this study may be permitted to
re-screen. Re-screening may be permitted on a case-by-case basis following a discussion
between the Principal Investigator (PI) and the Medical Monitor regarding whether a participant
remains potentially eligible to participate in the study. A participant who is re-screened is not 
required to sign another ICF if the re-screening occurs within 30 days from the previous ICF 
signature date. There is no minimum period of time a participant must wait to re-screen for the 
study. The participant must meet all eligibility criteria at the time of re-screening in order to 
qualify for the study. Depending upon the time from the last screening visit, the Medical Monitor 
will determine what assessments need to be repeated.


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 9 of 37
The study start date is defined as the date on which the first Informed Consent is signed. A 
participant is considered to have completed the study if he/she has completed all study visits. The 
end of the study is defined as the date of the last visit or the date of the last procedure of the last 
participant in the study.
3.2.
Sample Size and Power
The sample size justification in the protocol was as follows: for this trial, groups of 48 active-
dosed participants per dose level are felt to give adequate sensitivity to detect AEs. A sample 
size of 48 active-dosed participants for each dose level (100 mg/day, 300 mg/day) has 91% 
power to detect at least one occurrence of any drug-related AE with a true prevalence in the 
treated population of 5%.
Additional participants may be added to replace participants with significant disruption to their 
visit schedule due to COVID or if there are unanticipated dropouts.
Additionally, for the primary exploratory efficacy analysis relating to the ADAS-COG 11 
comparing the combined CT1812 treatment groups versus the placebo group, 48 participants per 
group provides 81% power to show a treatment difference of 3.0 points assuming a two-sided 
test at the alpha=0.05 level of significance, assuming a SD of 5.4 points, and a dropout rate of 
15%.
3.3.
Study Population
The study population will consist of male and female participants, 50 to 85 years of age 
(inclusive), with a diagnosis of mild to moderate AD according to the 2011 National Institute on 
Aging -
(NIA-AA) criteria and at least a 6-month decline in cognitive 
function documented in the medical record.
3.4.
Treatments Administered
Participants who meet eligibility criteria will be randomized to one of three treatment arms 
(CT1812 at doses of 100 mg/day or 300 mg/day or placebo). Study drug will be administered 
orally once each morning (i.e., prior to 12 pm) for 6 months. 
3.5.
Method of Assigning Participants to Treatment Groups
Participants will be randomized in a 1:1:1 ratio to CT1812 100 mg/day, CT1812 300 mg/day or 
placebo. The placebo will be identical in appearance to the active CT1812. The unblinded 
statistician assigned to the trial will generate a randomization list with the appropriate number of 
4--digit individual study identification numbers (IDs) for each arm, randomly assigned to one of 
the treatment arms.
3.6.
Blinding and Unblinding
This is a double-blind study. All participants, investigators, and study personnel involved in the 
conduct of the study will be blinded to treatment assignment, with the exception of a specified 
unblinded statistician who will generate and have access to the randomization code. The 
unblinded study personnel will not otherwise participate in study procedures or data analysis 
prior to unblinding of the study data.


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 10 of 37
If a safety stopping rule (defined in Section 7.3.1 of the study protocol) is achieved, selective 
unblinding of the participants involved may be performed by the Sponsor to determine if the AEs 
(serious or otherwise) are isolated to a single dose group or if they occurred in placebo 
participants.
3.7.
Schedule of Events
A detailed schedule of events for the study is provided in Table 1. 


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 11 of 37
Table 1: Schedule of Events
Screen
Base-
line
Study day(s)
-60 to
-1
1
3
(±1)
7
(±2)
14
(±2)
21
(±2)
28
(±2)
42
(±2)
56
(±2)
70
(±2)
90 
(±2)
98,126,
154
(±2)
172 
(±2)
182
(±2)
210
(±2)
Visit(s)
1
2
3*
4
5
6*
7
8
9
10
11,12
,13
14
Safety 
Follow 
Up 15
Screening Tests
1
Informed consent
X
2
Inclusion/Exclusion Criteria
X
X
3
Demography & Medical 
History
X
4
Confirm AD diagnosis
X
5
MMSE
X
X
X
X
(Day 
98)
X
6
Modified Hachinski exam and 
GDS
X
7
ApoE Status
X
8
Optional whole blood sample 
for future biomedical research
X
9
Screening Laboratories
X
Physical Exam, Vitals, ECG, Other
10
Complete Physical Exam 
X
X
X
11
Brief Physical Exam
X
X
X
X
X
X
X
X
X
12
Vital signs and weight
X
X
X
X
X
X
X
X
X
X
X
X
X
13
ECG (12-lead)
X
X
X
X
X
(Day 
98)
X
14
MRI
X
X
15
Amyloid PET Scan
X


Statistical Analysis Plan, 
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Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 12 of 37
Screen
Base-
line
Study day(s)
-60 to
-1
1
3
(±1)
7
(±2)
14
(±2)
21
(±2)
28
(±2)
42
(±2)
56
(±2)
70
(±2)
90 
(±2)
98,126,
154
(±2)
172 
(±2)
182
(±2)
210
(±2)
Visit(s)
1
2
3*
4
5
6*
7
8
9
10
11,12
,13
14
Safety 
Follow 
Up 15
Blood Draws, Urine Collection & Lumbar Puncture
16
Chemistry & hematology
X
X
X
X
X
X
X
X
X
X
X
X
X
17
Serum cystatin C
X
X
X
X
X
X
X
X
X
18
PK and Exploratory 
Biomarkers Sampling
X
EB 
only
X
X
X
X
X
X
X
X
X
19
Serum biomarkers
X
X
X
20
Coagulation testing (PT/INR)
X
X**
X
(Day 
154)
21
Optional lumbar puncture
(CSF Biomarker Sampling)
X
X
(Day 
98**
*)
X
22
Urinalysis
X
X
X
X
X
X
X
X
X
X
X
23
Pregnancy testing
X
Cognitive, Functional, and Safety Assessments
24
C-SSRS
X
X
X
X
X
X
X
X
X
X
X
X
X
25
Cognitive Assessments and 
ADCS-ADL
X
X
X
X
(Day 
98)
X
ADCS-CGIC
X
X
X
(Day 
98)
X
Concomitant Medications, Adverse Events and Study Drug Administration
26
Concomitant Medications
X
X
X
X
X
X
X
X
X
X
X
X
X
27
Adverse Events Assessment
X
X
X
X
X
X
X
X
X
X
X
X
28
Drug Accountability
X
X
X
X
X
X
X
X
X
X


Statistical Analysis Plan, 
Sponsor Cognition Therapeutics, Inc.
Protocol Number COG0201
PCN Number COGN187880
AD-ST-33.05 Effective date: 22-Jan-2018
Version Final 2.0 | 23May2024
Page 13 of 37
Screen
Base-
line
Study day(s)
-60 to
-1
1
3
(±1)
7
(±2)
14
(±2)
21
(±2)
28
(±2)
42
(±2)
56
(±2)
70
(±2)
90 
(±2)
98,126,
154
(±2)
172 
(±2)
182
(±2)
210
(±2)
Visit(s)
1
2
3*
4
5
6*
7
8
9
10
11,12
,13
14
Safety 
Follow 
Up 15
29
Drug Dispensation
X
X
X
X
X
30
In office dose administration
X
X
X
X
X
X
X
X
X
X
X
-
Cognition subscale; ADCS-ADL = ADCS-Activities of Daily 
Living Scale; ADCS-CGIC = ADCS-Clinical Global Impression of Change; ApoE = apolipoprotein E; C-SSRS = Columbia Suicide Severity Rating Scale; ECG 
= electrocardiogram; GDS = Geriatric Depression Scale; LP = lumbar puncture; MMSE = Mini Mental State Exam; MRI = Magnetic Resonance Imaging scan; 
NTB = Neuropsychological Test Battery; PET = Positron Emission Tomography scan; PK = pharmacokinetic; PT/INR = prothrombin time and international 
normalized ratio
* Study Visit 3 (Day 3) and Visit 6 (Day 21) will not be performed for participants enrolled in Part C.
** Only required on Day 70 if the optional LP on Day 98 is planned.
***If a participant and investigator are agreeable, an additional LP may be performed at least 24 hours before the Day 98 visit. 
If adequate volume is available, CSF will be stored for future evaluation of biomarkers of target engagement or disease modification. See Laboratory Procedures 
Manual for sample handling. See Section 11.5 for details. Obtained CSF should be sent for cell counts (white blood cells and red blood cells, with differential if 
either of the counts is abnormal), CSF protein, and CSF glucose at Screening, Day 98 (optional), and Day 182. If abnormalities are observed at Screening, they 
should be discussed with the Medical Monitor before randomizing the participant.
1.
Informed consent must be obtained prior to the participant undergoing any study-specific procedures.
2.
Review of all criteria detailed in Sections 9.2 and 9.3 of protocol.
3.
Record demographic information, confirm ethnicity and obtain medical history.
4.
Confirm AD diagnosis in accordance with McKhann 2011 criteria. 
5.
Mini Mental State Exam and Geriatric Depression Scale.
6.
Perform Modified Hachinski Exam to screen for vascular dementia.
7.
ApoE genetic testing is required for all participants.
8.
Optional whole blood sample (~10 mL) for future biomedical research, including potential genetic analyses.
9.
Screening labs include viral serology, Thyroid-stimulating hormone (TSH), Follicle-stimulating hormone (FSH) and Hemoglobin A1c (HbA1c).
10. Complete physical examination = thorough examination of all body systems, including height, weight, and neurological exam. Weight should be measured 
on the same scale each time. Height measured only at screening.


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11. Brief physical examination = inquire about signs/symptoms, review of general appearance and brief review of body systems, including weight. Weight 
should be measured on the same scale each time.
12. Vital signs will include body temperature, systolic and diastolic BP, respiration rate and pulse rate. Weight should also be recorded. At Baseline and 
subsequent visits, vital signs are done at pre-dose. 
13. ECG to be conducted during screening period, and approximately two hours post-dose (+/- 45 min) at specified visits.
14. MRI (or CT scan due to contraindication of MRI if approved by medical monitor) performed at screen (if an historical MRI is not used) and end of 
treatment.
15. Diagnostic confirmation by amyloid PET with florbetaben or another approved amyloid PET ligand. Diagnostic confirmation by cerebrospinal fluid (CSF)
sample collected at Screen Lumbar Puncture, in place of the amyloid PET, will also be accepted.
16. Blood Chemistry and Hematology - Blood should be drawn within an hour of urine collection. 
17. Serum cystatin C: Blood should be drawn within an hour of urine collection. 
18. Plasma PK and Exploratory Biomarker Sampling: See Laboratory Procedures Manual for sample handling. PK will not be assessed at screen whereas the 
exploratory biomarker samples will be collected.
Serum biomarker samples are collected at any point during screening at least 24 hours prior to the Baseline Visit. Serum biomarkers will also be collected at 
Day 90 (+/- 2 days) and Day 172 (+/- 2 days).
This blood draw will be performed at a local lab. The local lab will include onsite laboratory facilities for collection and processing. Participants consented 
to Protocol version 2.0 on or after their Baseline visit are not required to have the Biomarker samples drawn on Day 90 or Day 172.
19. The serum samples should not be collected on the same day as the lumber puncture.
20. Coagulation testing includes prothrombin time and INR.
21. Optional lumbar puncture: Participants may opt to undergo lumbar puncture as part of screening, after all other eligibility criteria have been reviewed and 
approved by the medical monitor, at least 24 hours before the Baseline visit and again at Day 182 (the end of the dosing period). LP on the Day 182 visit 
should be performed minimally 24 hours prior to the other the Day 182 visit procedures (e.g., Day 181) and prior to dosing on that day. The optional 
screening visit lumbar puncture must not be performed without Medical Monitor approval.
22. Urine should not be first morning void. See Laboratory Procedures Manual for sample handling.
23. Pregnancy testing should include an assessment of FSH levels.
24. C-SSRS Screening/Baseline version used at screening visit, Since Last Visit version used at all other visits.
25. The ADAS-Cog 13, NTB, ADCS-ADL, and MMSE will be conducted during screening period, and prior to dosing at other visits. The ADCS-CGIC will be 
conducted beginning at Day 1, and all other visits with the cognitive assessments.
26. All concomitant medications will be recorded from screening through Day 210.
27. During Screening (post-consent), only SAEs related to a study-specific procedure will be collected. For all related AEs of moderate or severe intensity 
ongoing at the end of the study, follow-up will continue until the event has resolved to baseline severity, the event is assessed as stable by the Investigator, or 
the participant is lost to follow-up or the participants withdraws consent.
28. Study drug accountability will be performed via capsule count.
29. Dosing on non-study visit days will be self-administered at home. 
will be completed for the bottle 
returned by the participants
administered with, or without food.
30. Participants will be administered the first dose in the clinic on Day 1. Doses on study visit days will also be administered in the clinic. Dose should be 
administered with or without food.


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4.
Statistical Analysis and Reporting
This SAP is based on the approved clinical study protocol, version 6.0, dated 12-Jun-2023.
This SAP addresses the safety and efficacy objectives of the study and describes the statistical 
methods that are to be used for the interim and final analysis of the completed study.
The reader of this SAP is encouraged to also read the clinical protocol, Drug Safety and 
Monitoring Board (DSMB) charter, and any other identified documents, for details on the 
planned conduct of the study. Operational aspects related to collection and timing of planned 
clinical assessments are not repeated in this SAP unless relevant to the planned analysis.
4.1.
Introduction
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations will be performed primarily using SAS (release 9.4 or higher). If the 
use of other software is warranted, the final statistical methodology report will detail what 
software was used for what purposes.
Continuous (quantitative) variable summaries will include the number of participants (n) with 
non-missing values, mean, standard deviation (SD), median, minimum, and maximum. Other 
statistics such as coefficient of variation (%CV), quartiles, confidence intervals (CIs), and 
number of missing values may be added as appropriate. 
Categorical (qualitative) variable summaries will include the frequency and percentage of 
participants who are in the particular category or each possible value. In general, the 
denominator for the percentage calculation will be based upon the total number of participants in 
the study population within each treatment group, unless otherwise specified. The denominator 
for by-visit displays will be the number of participants in the relevant study population with non-
missing data at each visit.
The minimum and maximum will be reported with the same degree of precision (i.e., the same 
number of decimal places) as the observed data. Measures of location (mean and median) will be 
reported to 1 degree of precision more than the observed data. Measures of spread (SD) will be 
reported to 2 degrees of precision more than the observed data.
Percentages will be presented to 1 decimal place, unless otherwise specified.
Unless otherwise indicated, all statistical tests will be conducted at the 0.05 significance level 
using 2-tailed tests, and P-values will be reported. A P-value of 0.10 but >0.05 will be 
considered evidence of a trend. Corresponding 95% CIs will be presented for statistical tests.
4.2.
Interim Analysis and Data Monitoring
After the first 24 participants have been randomized and completed their last study visits, the 
database for those participants will be frozen for purposes of an unblinded interim analysis of 
safety and efficacy data. All statistical outputs planned for the final analysis at the time of the 
interim analysis will be generated for the interim analysis. After the data for the first 24 
participants is frozen, the unblinded statistician will provide randomization codes for these 


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participants only. These outputs will exclude any data from participants that are not part of the 
first 24 randomized participants. The data from the first 24 participants will also be included in 
the analysis of the final dataset.
A DSMB will oversee the safety of the trial. This committee will consist of independent experts, 
including an independent statistician. Safety data will be provided to the DSMB at quarterly 
intervals during the trial. The study clinician and study medical monitor will review trial safety 
data biweekly and more frequently as the safety data warrant. Similarly, more frequent ad hoc 
meetings of the DSMB will occur if ongoing safety data indicate interim meetings are indicated. 
Additional details can be found in the DSMB charter.
5.
Analysis Populations
The following analysis populations are planned for this study:
All Subjects: The All Subjects population includes all participants who sign the ICF and 
get screened for the study.
Safety Population (SAF): The Safety Population includes all participants who receive 
one or more doses of study medication.
Efficacy Modified Intent-To-Treat Population (mITT): The Efficacy mITT 
Population includes all randomized participants who receive any amount of study drug 
and who have a baseline and at least one post-baseline assessment of the ADAS-Cog 11 
total score.
Completers Population (CP): The Completers Population includes all randomized 
participants who completed the study (i.e., who did not prematurely withdraw). There is 
no expectation that a participant included in the CP will have attended every single 
scheduled visit; as long as the participant completed the study, they will be included in 
the population.
Pharmacokinetic Population (PK): The Pharmacokinetic Population includes all 
participants in the SAF who had at least one quantifiable concentration of CT1812.
6.
General Issues for Statistical Analysis
Table and figure outputs based on the Safety Population and all listings will be presented by 
actual treatment received. Table and figure outputs based on the PK Population will be presented 
by actual treatment received. Table and figure outputs based on the mITT Population and 
Completer Population will be presented by randomized treatment.
Generally, all table and figure outputs will present individual CT1812 dose groups (100 mg, 300 
mg) and the pooled CT1812 dose group (100 mg and 300 mg together) in addition to placebo.
6.1.
Statistical Definitions and Algorithms
6.1.1. Baseline
The last non-missing observation recorded on or before the first dose of study drug will be used 


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as the baseline observation for all calculations of change from baseline. 
6.1.2. Adjustments for Covariates
The efficacy models will include APOE 
Participants
6.1.3. Multiple Comparisons
Although all of the clinical efficacy analyses for this study are exploratory in nature, the ADAS-
Cog 11 least square mean change from baseline analysis is considered the primary exploratory
analysis of interest compared to the other clinical efficacy analyses. The primary exploratory 
analysis of the ADAS-Cog 11 will compare the least square mean change from baseline value for 
the two active arms combined to the least square mean change from baseline value for the 
placebo arm at day 182, using a two-sided test at the alpha=0.05 level of significance. If the 
primary exploratory analysis of the ADAS-Cog 11 is statistically significant, then the following 
comparisons will be made using the least square mean change from baseline values and the same 
model as for the primary analysis: 
1) 300 mg CT1812 versus placebo; 
2) 100 mg CT1812 versus placebo. 
Each comparison will be conducted using a two-sided test at the alpha=0.05 level of significance. 
This fixed sequence testing procedure will control the overall level of significance for this 
outcome. 
All other clinical efficacy analyses will be conducted using two-sided tests at the alpha=0.05 
level of significance. No adjustments will be made for multiple comparisons and all other p-
values will be considered nominal.
6.1.4. Handling of Dropouts or Missing Data
If a participant is missing one, two, or three individual components of the Cognitive Composite 
score at a time point, the Cognitive Composite score will be computed using the average of the 
non-missing components at the time point. If a participant is missing four or more 
individual components at a time point, the Cognitive Composite score will not be derived at that 
time point.
For the interim analysis, missing data for endpoints assessed at multiple time points will be 
imputed using the last observation carried forward (LOCF) approach. 
For the final analysis, missing data for endpoints assessed at multiple time points and analyzed 
using repeated measures models will not be imputed. Missing data for endpoints assessed at post 
baseline timepoints may be imputed using LOCF for the purpose of analyzing data using an 
Analysis of Covariance (ANCOVA) model when the MMRM model fails to converge.
For the interim and final analyses, missing data for endpoints assessed at only one post-baseline 
time point will not be imputed.


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6.1.5. Outlier Values and Values below the Limit of Quantitation
Some biomarker analyses may require removal of participants whose values are outliers or who 
have values at certain time points that are below the limit of quantitation. Decisions regarding 
inclusion or exclusion of participant values at particular timepoints will be made prior to 
database lock (DBL) and unblinding of data.
6.1.6. Analysis Visit Windows
Data in summary tables will be summarized by the nominal visit collected in the electronic data 
capture (EDC) system. The Day 182 (EOS or early termination [ET]) label in the EDC system is 
used for both Day 182 EOS visits and ET visits. A participant will only have their Day 182 data 
included in the summary tables if it occurs after study Day 170. Participants that early terminate 
before study Day 170 will have their ET visit listed only.
6.1.7. Pooling of Sites
Not applicable.
6.1.8. Derived Variables
Change from baseline = value at current time point value at baseline. 
Treatment-emergent AE (TEAE) = any AE with an onset date/time on or after the first 
dose of study drug.
Modified Hachinski total score = the sum of the individual 8 item scores. Items 1, 6, 7 & 
8 attract a score of 2-points if present (range of 0-8). Items 2, 3, 4 & 5 attract a score of 1-
point if present (range of 0-4). The total score ranges from 0 12.
o
The sites were originally responsible for manually calculating the total score and 
entering it into the clinical study database. To ensure accuracy, it was decided to 
re-derive this total score in the ADaM dataset. 
ADCS-ADL total score = the sum of the individual 23 item scores. The score ranges from 
0-78.
o
The sites were originally responsible for manually calculating the total score and 
entering it into the clinical study database. To ensure accuracy, it was decided to 
re-derive this total score in the ADaM dataset
The ADAS-13 total score = the sum of all 13 individual items (word recall; commands; 
constructional praxis; delayed word recall; naming objects and fingers; ideational praxis; 
orientation; word recognition; remembering test instructions; spoken language; word 
finding; comprehension of spoken language; and number cancellation). 
o
The score for the number cancellation item was originally set up to be derived 
within the clinical study database, however prior to database lock, an error was 
discovered in the derivation of this item score. This error subsequently impacts 


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the derivation of the ADAS-13 total score, which was also originally set up to be 
derived within the clinical study database. 
o
As a result, both the number cancellation item score and the ADAS-13 total score 
will be re-derived in the ADaM dataset for analysis purposes as follows:
o
The number cancellation score will be derived in two steps: 
Step 1: Calculate the preliminary number cancellation item score as 
(number of targets hit)
[(number of errors) + (number of times to remind 
to task)]
Step 2: Take the preliminary number cancellation item score calculated in 
Step 1 and re-scale as follows:
If number cancellation item score is
30 then re-scale as 0
-scale as 1
-scale as 2
-scale as 3
-scale as 4
-scale as 5
o
Number cancellation item scores < 0 will be re-scaled as 5
The resulting final number cancellation item score will range from 0 to 5.
o
The ADAS-13 total score will be derived as the sum of the 13 individual items, 
but using the score for the number cancellation item which has been re-derived as 
described above.
The ADAS-11 total score is the sum of 11 individual items excluding delayed recall and 
number cancellation.
The Cognitive Composite score will be calculated using z-scores of the below items. The 
z-scores will be derived by calculating the baseline mean and standard deviation of each 
individual component for all participants. A z-score within each component will be 
derived for each participant at each timepoint by subtracting the corresponding baseline 
mean and then dividing by the corresponding baseline SD. The Cognitive Composite 
score will be set as the mean of the 10 individual z-scores (5 ADAS-COG scores and 5 
NTB scores) within each participant and timepoint. If a participant is missing one, two, or 
three scores at a particular timepoint, the missing scores will be set as the average non-
missing z-score of all participants at that timepoint within each component when deriving 
the Cognitive Composite score. If a participant is missing four or more individual 
components at each timepoint, the Cognitive Composite score will not be derived.
o
ADAS-COG
Word recall (scored on a 0 to 10 range), average of trials I, II, and III. If at 
least one of the trials is missing, this component will be considered 
missing. The sign of the z-score for this component will be reversed when 
deriving the Cognitive Composite score as it is the total words not recalled 
that is being recorded. This test is a key measure of episodic memory.


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Orientation (0 to 8). The sign of the z-score for this component will be 
reversed when deriving the Cognitive Composite score as the recorded 
score for this test is the number of items answered incorrectly. This 
measure is an index of the study 
episodic memory and a 
single item of semantic memory (their name). 
Delayed Word Recall (0 to 10). The sign of the z-score for this component 
will be reversed when deriving the Cognitive Composite score as it is the 
total words not recalled that is being recorded.
Word Recognition (0 to 24). The sign of the z-score for this component 
will be reversed when deriving the Cognitive Composite score. This is a 
further test of episodic memory using a word recognition paradigm of 12 
true positive targets and 12 foil items. While the possible score for this 
measure is 0 to 24, the standard ADAS-Cog score is capped at a maximum 
worst score of 12.
o
Number Cancellation (raw score 0 to 40, subsequently re-scaled to a 5-point scale 
[0-5]). In this task, the participant is asked to cross off as many target digits as 
possible in 45 seconds. The score is derived as the number of incorrectly crossed-
off items and the number of reminders given subtracted from the number of items 
correctly crossed off. The resulting score (0-40) is then re-scaled to a 5-point scale 
(0-5) as described earlier in this section. NTB
COWAT This test of working memory and executive function yields a 
deemed acceptable according to the scoring rules. The total score for 
COWAT is the sum of the number of accepted words for each of the 3 
tests (three letters). The score range for this test is typically between 0 and 
80, though floor performance (a score of 0) is vanishingly rare in mild-to-
moderate stage AD participants.
CFT This is a further test of working memory and executive function 
This is obtained by calculating how many of the study 
responses are deemed acceptable according to the scoring rules. The usual 
performance range for this test is between 0 and 40.
Digit Span This is a brief measure of working memory, especially in the 
Digits Backwards section. The key metric 
the test is 0 to 24 and both floor and ceiling effects are rare.
Trail Making Test (TMT) A This is essentially a measure of attention, as 
successful completion relies on quickly and accurately connecting 
numbered circles in an ascending sequence. The key metric for analysis 


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both contribute to performance. However, because errors incur a time 
penalty, it is not necessary to analyze both metrics. The sign of the z-score 
for this component will be reversed when deriving the Cognitive 
Composite score.
Trail Making Test (TMT) B This is the more complex component of the 
TMT in which successful completion relies on the study participant
accurately connecting the numbered and lettered circles. Study 
participants are required to alternate between numbers and letters in an 
me 
penalty, it is not necessary to factor in errors for analysis purposes. The 
sign of the z-score for this component will be reversed when deriving the 
Cognitive Composite score.
The Memory composite score will be a composite z-score average similar to the 
Cognitive Composite score but will only be derived using the average of the ADAS-Cog 
Word Recall, Orientation, Delayed Word Recall, and Word Recognition items. If a 
participant is missing any of the four items at a timepoint, this composite score will not 
be derived.
The Attention composite score will be a composite z-score average derived using the 
average of the Number Cancellation and TMT A items. If a participant is missing either 
of the two items at a timepoint, this composite score will not be derived.
The Executive function composite score will be a composite z-score average derived 
using the average of the COWAT, CFT, Digit Span, and TMT B items. If a participant is 
missing any of the four items at a timepoint, this composite score will not be derived.
6.1.9. Data Adjustments/Handling/Conventions
All collected data will be presented in listings. Data not subject to analysis according to this plan 
will not appear in any tables or graphs but will be included only in the data listings.
All P-values will be displayed in four decimals and rounded using standard scientific notation 
(e.g., 0.XXXX). If a P-value less than 0.0001 occurs, it will be shown in tables as < 0.0001. If a 
P-value greater than 0.9999 occurs, it will be shown in tables as > 0.9999.
Adverse events and medical history will be coded using the latest version of the Medical 
Dictionary for Regulatory Activities (MedDRA) thesaurus available at the time of database lock.
Prior and concomitant medications will be coded using the latest version of World Health 
Organization - Drug Dictionary Enhanced (WHO-DDE) available at the time of database lock.
A treatment-related AE is any AE with a relationship to the study drug of probable or possible.
If it is necessary to calculate a 
age from the (partial or complete) date of birth


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(DOB) and the date of the Baseline Visit, the floor function will be used to ensure the participant
has an integer age.
If partial AE dates or partial medication dates occur, the convention for replacing missing dates 
for the purposes of calculating derived variables is as follows:
For partial AE and medication start dates:
If the year is unknown, then do not impute the date but instead assign a missing value.
If the year is known, but the month or month and day is unknown, then:
o
If the year matches the year of first application date and the end date (if present) is 
after first dose date, or AE/medication is ongoing, then impute as the month and 
day of the first application date. If this produces a date after the AE/medication 
end date, assign 01 January.
o
Otherwise, assign 01 January.
If the year and month are known, but the day is unknown, then:
o
If the month and year match the month and year of the first dose date, then impute 
as the day of the first dose date. If this produces a date after the AE/medication 
end date, assign 01.
o
Otherwise, assign 01.
For partial AE and medication end dates:
If the year is unknown, then do not impute the date but assign as missing value.
If the year is known but the month or month and day is unknown, then:
o
If the year matches the year of the last date of the study (date of last contact if 
participant is lost to follow-up; date of completion or early termination 
otherwise), then impute as the month and day of the last date of the study.
o
Otherwise, assign 31 December.
If the year and month are known, but day is unknown, then:
o
If the month and year match the month and year of the last date of the study, then 
impute as the day of the last date of the study.
o
Otherwise, assign the last day of the month.
quantitation (LLOQ) will be used for analysis (i.e., the value of X will be used in the analysis for 
X will be used in the analysis for lab values repo
For analysis purposes, repeat laboratory test results will not be used unless the original 
laboratory value is missing or indicated as invalid, in which case the first non-missing repeated 
laboratory value will be used for data analysis.


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Data missing in the exploratory analysis of phospho-tau proteins will be handled according to the 
SAP provided by Proteome Sciences. 
6.1.10. Subgroups
The following subgroups are defined for this study:
Subgroup
Definition/Levels
Measurable PK at 
Multiple Timepoints
If a participant randomized to CT1812 has measurable (>BLOQ) 
CT1812 concentrations at 7 or more post-baseline timepoints at which 
PK was assessed, then they are included in the subgroup.
All participants randomized to placebo with CT1812 concentrations 
BLOQ at all post-baseline timepoints at which PK was assessed are 
included in the subgroup.
Analyses will summarize all participants who meet the criteria to be 
included in the subgroup. It is not of interest to compare participants 
who meet the criteria for inclusion in this subgroup vs. those who 
Sex
Male, Female
MMSE at Baseline
18-21, 22-26
Age
<65, >=65
ApoE Status at 
Baseline
Positive, Negative. 
If genotype ApoE or phenotype ApoE contains E4, then ApoE status 
is considered Positive. Otherwise Negative.
pTau217 at Baseline
<Median, >=Median 
Median value is determined based on all participants combined 
(regardless of treatment group). This subgroup is based on plasma 
biomarker samples (not CSF).
Pre/Post COVID
Pre-COVID: Includes participants who completed or prematurely 
withdrew from the study prior to March 10, 2020. 
Post-COVID: All remaining participants
Region
US, ex-US (EU + AUS)
Acetylcholinesterase 
(AChE) inhibitors 
and/or memantine 
Yes: Participant took these medications during the treatment period
No: Participant did not take these medications during the treatment 
period


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Subgroup
Definition/Levels
use during the study
The following medications will be considered for this subgroup:
Any medication containing donepezil (Aricept, Namzaric), 
rivastigmine (Exalon), galantamine (Razadyne, Reminyl), or tacrine 
(Cognex) is considered an AChE inhibitor.
Any medication containing memantine (Namenda, Namzaric) is 
considered memantine.
7.
Study Participants and Demographics
7.1.
Disposition of Participants and Withdrawals
The number of participants randomized and treated will be summarized by treatment group. The 
number and percentage of participants in the Safety, mITT, Completers, and PK Populations will 
be summarized by treatment group. The number and percentage of participants who completed 
the study and who prematurely discontinued the study will be summarized by treatment group. 
The reasons for study discontinuation will also be summarized. 
All disposition information will be listed.
7.2.
Protocol Violations and Deviations
Protocol deviations will be listed.
7.3.
Demographics and Other Baseline Characteristics
Demographic variables such as age, sex (including child-bearing potential for female), ethnicity, 
and race, and baseline characteristics such as height, weight, and body mass index (BMI), 
highest Level of Education, ApoE4 Status, ApoE Genotype, and Mini Mental State Exam 
(MMSE) Total Score will be summarized by treatment group for the Safety and mITT (if 
different from Safety) Populations. 
Categorical variables, such as sex, ethnicity, race, and level of education will be summarized 
using frequencies and percentages. Continuous variables such as age, height, weight, and BMI 
will be summarized using mean, SD, median, minimum, and maximum.
Medical history will be coded using the latest version of MedDRA at the time of database lock. 
Medical history information will be listed only.
Demographic information will also be listed.
7.4.
Exposure and Compliance
For all of the below formulas, i = individual participant for the entire treatment period.
Total days of exposure will be calculated as:


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Study drug compliance will be calculated as:
Compliance will be calculated using drug accountability data over the entire treatment period for 
each participant, up to treatment completion or discontinuation. Planned capsules will be 
calculated as 2 × the number of days between the first and last dose of study drug (inclusive).
Study drug exposure and compliance information will also be listed.
8.
Efficacy Analysis
All efficacy analyses are exploratory in nature. The intent of this plan is to run the analysis of 
covariance (ANCOVA) model described in section 8.1 at the time of the interim analysis and the 
mixed-model repeated measures (MMRM) model described in section 8.1 at the time of the final 
analysis. However, if the MMRM model fails to converge, the ANCOVA analysis (with both 
observed and observed + LOCF values) will be run in place of the MMRM model for the final 
analysis. A Day 182 visit will be considered out-of-window if it does not occur between study 
day 171 and study day 193 (inclusive).
For the final analysis, all efficacy analyses will be run using the mITT population and a subset of 
the efficacy parameters (ADAS-Cog 11, ADCS-ADL, MMSE, ADCS-CGIC) will be 
summarized using the Completers Population as a sensitivity analysis. 
All figures will be based on the mITT population only. The following figures will be produced 
for each efficacy parameter (ADAS-Cog 11, ADCS-ADL, MMSE, ADCS-CGIC and the 
composite z-scores: Cognitive Composite score; Memory Composite score; Attention Composite 
score; and Executive Function Composite score):
Line plot of change from baseline values.
Line plot of least square mean change from baseline values.
By-participant spaghetti plots of the change from baseline values.
8.1.
Composite z-scores
The composite z-scores (Cognitive Composite score; Memory Composite score; Attention 
Composite score; and Executive Function Composite score) defined in Section 6.1.8 will have 
their observed values and change from baseline summarized by visit.
Mean change from baseline within each of the four composite z-scores will be analyzed using a 
MMRM analysis with treatment as the main effect, visit, baseline z-score of the corresponding 
composite score, APOE 


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APOE 
8.2.
Mini Mental State Exam (MMSE)
The MMSE is a brief, screening instrument often used in clinical trials to assess dementia 
severity. The MMSE assesses several aspects of memory and cognitive functioning including 
orientation, attention, concentration, comprehension, recall, and praxis. The total possible score 
is 30, with high scores indicating less impairment.
Descriptive summaries of observed values and changes from baseline in the MMSE total score 
will be calculated by visit. 
Change from baseline for MMSE will be analyzed using the same MMRM model described in 
Section 8.1, with the MMSE score in place of the composite score. 
8.1
For the final analysis, MMSE will be summarized and analyzed for both the mITT Population 
and the Completers Population. Additionally, the change from baseline in MMSE will be 
summarized and analyzed for each subgroup defined in Section 6.1.10 using the mITT 
Population. For the subgroup analysis by ApoE status at Baseline, the APOE covariate will be 
excluded from the statistical model.
Results for MMSE will be listed.
8.3.
-Cognition Subscale (ADAS-Cog 14)
The ADAS-Cog 14 is a widely used general cognitive measure in clinical trials of AD. The 
ADAS-Cog was developed as an outcome measure for dementia interventions; its primary 


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purpose was to be an index of global cognition in response to antidementia therapies. The 
ADAS-Cog assesses multiple cognitive domains including memory, language, praxis, and 
orientation. For this study, 13 items of the ADAS-Cog 14 will be assessed.
Descriptive summaries of observed values and changes from baseline in the ADAS-Cog 13 
(ADAS-13) total score and ADAS-Cog 11 (ADAS-11) total score will be calculated by visit.
ADAS-13 and ADAS-11 change from baseline will be analyzed using the same MMRM model 
described in Section 8.1, with baseline ADAS-13 or ADAS-11 score in place of the composite 
baseline score. 
8.1
For the final analysis, ADAS-13 and ADAS-11 will be summarized and analyzed for both the 
mITT Population and the Completers Population. Additionally, the change from baseline in 
ADAS-13 and ADAS-11 will be summarized and analyzed for each subgroup defined in Section 
6.1.10 using the mITT Population. For the subgroup analysis by ApoE status at Baseline, the 
APOE covariate will be excluded from the statistical model.
ADAS-Cog results will also be listed.
8.4.
Neuropsychological Test Battery (NTB)
The NTB consists of TMT A and TMT B, Digit Span, COWAT, and CFT. The TMT A and 
TMT B marking duration in seconds, Digit Span, CFT, and COWAT, tests will be summarized 
by visit and treatment. The composite scores for each item defined in Section 6.1.8 will be 
summarized by visit and treatment.
The change from baseline for each NTB component score will be analyzed using the same 
MMRM model described in Section 8.1.
8.1
Results for NTB will also be listed.
8.5.
ADCS-Clinical Global Impression of Change (ADCS-CGIC)
The ADCS-
scale consists of a format with which a clinician may address clinically relevant overall change, 
including 15 areas under the domains of cognition, behavior, and social and daily functioning. 
The rater, at baseline, interviews the participant and caregiver/informant, using a form that 
comprehensively lists relevant symptoms potentially useful in judging change, and makes notes 
for future reference. There are few requirements to fulfill during the interview, but clinical 
assessment of mental status is to be made. By allowing raters to use the forms in an unstructured 
manner, this scale may facilitate clinical judgements with face validity. At follow-up visits, the 


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clinician uses a similar set of forms to re-interview the participant and caregiver/informant. The 
ADCS-CGIC rating is made on a 7-point scale similar to other global change scales, where a 
lower score indicates marked improvement. The ADCS-CGIC value is a measure of the change 
from baseline and therefore the algebraic change from baseline is not calculated for the 
ADCS-CGIC. As available at the site, the ADCS-CGIC will be completed by an independent 
rater (not the rater completing the cognitive or other assessments).
Descriptive numeric summaries of observed values in the ADCS-CGIC will be calculated by 
visit. 
Observed values for ADCS-CGIC will be analyzed using the same MMRM model described in 
Section 8.1. Since an ADCS-CGIC result is not collected at baseline, no baseline covariate will 
be included in the model.
8.1
For the final analysis, ADCS-CGIC will be summarized and analyzed for both the mITT 
Population and the Completers Population. Additionally, the observed values for ADCS-CGIC 
will be summarized and analyzed for each subgroup defined in Section 6.1.10 using the mITT 
Population. For the subgroup analysis by ApoE status at Baseline, the APOE covariate will be 
excluded from the statistical model.
Results of ADCS-CGIC will also be listed.
Additionally, frequencies and percentages in the ADCS-CGIC will be summarized by visit. 
Cochran-Mantel-Haenszel mean score statistics, using rank scores, and stratified by ApoE status, 
will be used to assess the difference in ADCS-CGIC responses at each visit between the CT1812 
dose levels and placebo. 
8.6.
ADCS-Activities of Daily Living (ADCS-ADL)
The ADCS-ADL is a 23-item informant-administered assessment of functional impairment in 
terms of activities of daily living. Informants respond to 23 questions about the participa
involvement and level of performance across items representing daily living. The questions 
range from basic to instrumental activities of daily living. Each item is rated from the highest 
level of independent performance to complete loss. The total score range is from 0 to 78 with 
lower scores indicating greater functional impairment.
Descriptive summaries of observed values and changes from baseline in the ADCS-ADL total 
score will be calculated by visit. 
Change from baseline for ADCS-ADL will be analyzed using the same MMRM model described 
in Section 8.1, with the ADCS-ADL score in place of the composite score. 
8.1


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For the final analysis, ADCS-ADL will be summarized and analyzed for both the mITT 
Population and the Completers Population. Additionally, the change from baseline in ADCS-
ADL will be summarized and analyzed for each subgroup defined in Section 6.1.10 using the 
mITT Population. For the subgroup analysis by ApoE status at Baseline, the APOE covariate 
will be excluded from the statistical model.
Results of ADCS-ADL will also be listed.
8.7.
Cognitive Composite Score and its Components
Descriptive summaries of observed values and changes from baseline will be calculated by visit.  
The results will also be listed.
8.8.
Biomarker Changes
Targeted measurements of several protein biomarkers in CSF and plasma will be made, 
including the following: 
Biology
Biomarker
Biofluid
AD progression disease
CSF, plasma
Total Tau
CSF
pTau181
CSF, plasma
pTau217
plasma
Brain derived Tau (BD-Tau)
plasma
Synaptic function
Neurogranin
CSF
Synaptotagmin 1, SNAP25
CSF
Neuroinflammation
GFAP
CSF, plasma
Neurodegeneration
NFL
CSF, plasma
Other
Alpha-Syn
CSF
CT1812 treatment at 6 months. For all remaining biomarkers, it is hypothesized that changes will 
be observed over the 6-month treatment period.
Descriptive summaries of observed values and changes from baseline for each plasma and CSF 


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biomarker will be calculated by visit. 
Plasma samples will be analyzed at baseline (V2), V11 (Day 98), and Day 182. Assuming data 
for more than one post-baseline sample is available, the change from baseline for each plasma 
biomarker will be analyzed using the same MMRM model described in Section 8.1. If only one 
post-baseline sample is available, then the ANCOVA model detailed below will be used.
for analysis of the CSF biomarkers at the final analysis, and in the 
scenario where only one post-baseline plasma biomarker sample is available at the final analysis,
of change from baseline values
8.1 For CSF, only screening (V1) and V14 (Day 182) biomarker samples were 
collected and biomarkers will be measured in CSF from V1 and V14 and will be analyzed in the 
final analysis.
For the analysis of phospho-tau proteins performed for the interim analysis only, ANOVA 
analysis of the log2 (fold change from baseline) will be used to assess significance of drug 
effects.
For the final analysis, the change from baseline in each biomarker will be summarized and 
The following rules will apply to the subgroup analyses:
If less than 10 participants fall into any one treatment group/level of a subgroup, then the 
corresponding summary/analysis for that subgroup will not be conducted.
If at least 10 participants fall into all treatment groups/levels of the subgroup, then the 
corresponding summary/analysis for that subgroup will be conducted.
These rules will be applied separately for the subgroup analyses which compare 
individual CT1812 dose groups vs. placebo and for those which compare the pooled 
CT1812 dose group vs. placebo. It is possible that these criteria will not be met for the 
analysis based on individual CT1812 dose groups, but once the CT1812 dose groups are 
pooled, the criteria are met.
For the final analysis, the following figures will be produced:
Spaghetti plots displaying individual participant-level data of observed values over time 
for each plasma and CSF biomarker by treatment group (placebo, CT1812 100 mg, 
CT1812 300 mg). The mean value for each treatment group will be overlayed and 
presented as a bold line in the body of the figure. These will be formatted as 3-panel, 
side-by-side plots, where each treatment group is presented in their own panel and all on 
the same Y-axis.
Line plots displaying the mean (±SD) observed values over time for each plasma and 
CSF biomarker by treatment group (placebo, CT1812 100 mg, CT1812 300 mg, pooled 
CT1812 100 mg+300 mg).
Line plots displaying the mean (±SD) change from baseline values over time for each 
plasma biomarker by treatment group (placebo, CT1812 100 mg, CT1812 300 mg, 
pooled CT1812 100 mg+300 mg).
Line plots displaying the mean (±SD) change from baseline values at Day 182 for each 
CSF biomarker by treatment group (placebo, CT1812 100 mg, CT1812 300 mg, pooled 


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CT1812 100 mg+300 mg) and plotted in this order from left to right in the figure.
Line plots displaying the LS mean (±95% CI) change form baseline values for each 
plasma and CSF biomarker by treatment group (placebo, CT1812 100 mg, CT1812 300 
mg, pooled CT1812 100 mg+300 mg) and plotted in this order from left to right in the 
figure.
Vertical scatter plots displaying the individual participant-level data of change from 
baseline values at Day 182 for each CSF biomarker by treatment group (placebo, CT1812 
100 mg, CT1812 300 mg, pooled CT1812 100 mg+300mg) and plotted in this order from 
left to right in the figure.
All biomarker data will also be listed.
8.9.
Other Exploratory Efficacy Analyses
Pearson correlation coefficients will be used to assess associations between biomarkers and 
cognitive and behavioral changes (ADAS-13, ADAS-11, Memory Composite, Attention 
Composite, NTB individual items, Executive Function Composite, Cognitive Composite, 
MMSE, ADCS-ADL, and ADCS-CGIC). Correlations will be calculated for baseline biomarker 
values and baseline efficacy measures. Additionally, correlations between change from baseline 
in by-visit biomarker values and change from baseline in efficacy scales will be calculated, and 
correlations between observed values in by-visit biomarker values and observed values in 
efficacy scales will be calculated.
CT1812 concentrations in CSF and plasma will also be correlated with changes from baseline in 
biomarkers and cognitive measures. 
Additional analyses and correlations may be explored as well (e.g., possibly including age, 
gender, education and ApoE) and will be discussed in the clinical study report (CSR).
9.
Safety and Tolerability Analysis
Safety assessments will be performed at scheduled timepoints throughout the study and include 
physical examination, vital signs, ECGs, standard clinical laboratory testing (serum chemistry, 
hematology, urinalysis), C-SSRS, prior and concomitant medications (CMs), and AEs.
All safety analyses will be performed on the Safety Population by actual treatment received.
9.1.
Adverse Events
Treatment-emergent AEs will be summarized in all AE tables. A TEAE is defined as any AE 
with an onset date/time on or after the first dose of study drug. All AE summary tables will 
include the number and percentage of participants with an AE within a category, system organ 
class (SOC), or preferred term (PT).
An overall summary of the number and percentage of participants with TEAEs will be provided 
by treatment group. Frequencies and percentages of the following will be included: with any 
TEAE, participants with any TEAE related to treatment, participants with any TEAE leading to 


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treatment discontinuation, participants with any serious treatment emergent AE (SAE), 
participants with any SAE related to treatment, and participants with any TEAE leading to death.
The incidence of TEAEs will be summarized with frequencies and percentages by the following:
PT in descending order of frequency
SOC and PT
SOC, PT, and maximum severity (Mild; Moderate; Severe)
SOC, PT, and maximum relationship to study drug (Not Related; Related)
Incidences other than the PT summary will be presented alphabetically by SOC and PT. 
Participants with multiple events within the same SOC and PT will be counted once per SOC and 
PT. TEAEs with a missing severity will be considered severe and TEAEs with a missing 
relationship to study drug will be considered related. AEs with a relationship of study drug of 
possibly or probably related will be considered related.
All AEs will be presented in a listing. AEs that are treatment emergent will be flagged.
9.1.1. Adverse Events Leading to Withdrawal
A summary of incidence rates (frequencies and percentages) of TEAEs leading to treatment 
discontinuation, by treatment group, SOC, and PT will be provided for the Safety Population.
A data listing of AEs leading to study drug discontinuation will also be provided, displaying 
details of the event(s) captured on the CRF.
9.1.2. Deaths and Serious Adverse Events
Any deaths that occur during the study will be listed.
Serious adverse events will be listed and also tabulated by SOC and PT and presented by 
treatment.
9.2.
Clinical Laboratory Evaluations
9.2.1. Protocol-Required Safety Laboratory Tests
Hematology testing will include erythrocyte (red blood cell count), erythrocyte mean corpuscular 
hemoglobin concentration (MCHC), erythrocyte mean corpuscular volume (MCV), hematocrit, 
hemoglobin, and absolute counts of leukocytes, lymphocytes, monocytes, neutrophils, basophils, 
eosinophils, and platelets. Coagulation testing (prothrombin time [PT/INR]) will be performed at 
screening and Day 154 only.
Serum chemistry analyses will include glucose, calcium, albumin, protein, sodium, potassium, 
bicarbonate, chloride, magnesium, fractional calcium excretion, blood urea nitrogen (BUN), 
creatinine, creatine kinase, alkaline phosphatase, Alanine Aminotransferase (ALT), Aspartate 
Aminotransferase (AST), bilirubin, lipase, lactate dehydrogenase (LDH), and phosphate.
Urinalysis will include osmolality, creatinine, calcium, erythrocytes, leukocytes, sodium, specific 


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gravity, pH, specimen appearance (turbidity), color, protein, glucose, ketones, bilirubin, 
hemoglobin, urobilinogen, nitrite, and microscopic particles. Trace protein will be considered 
positive. Urine samples that did not have preservative added prior to lab analysis will be listed 
only.
All summaries of laboratory values from local and central lab will be presented using SI units. 
Observed hematology, chemistry, and urinalysis values and changes from baseline at each visit 
will be summarized by treatment received. Shifts from baseline regarding low/normal/high 
values will also be summarized by treatment received. 
Shift tables summarizing the most extreme post-baseline shift for each participant within each 
lab parameter will be presented, with low and high results considered more extreme than normal. 
If a participant has both a low and high post-baseline result within a parameter, they will be 
counted within both the low and high rows.
The incidence of post-baseline ALT values >=3xULN, AST values >=3xULN, and AST or ALT 
values >=3xULN will be summarized.
All chemistry, hematology, and urinalysis data will be listed. 
Screening laboratory tests such as viral serology, thyroid stimulating hormone, follicle-
stimulating hormone, HbA1c, Folate, B12, and urine pregnancy test results will be listed only.
9.3.
Vital Signs
Descriptive summaries of actual values and changes from baseline will be calculated for systolic 
blood pressure (SBP [mmHg]), diastolic blood pressure (DBP [mmHg]), heart rate (beats/min), 
respiration rate (breaths/min), body temperature (C), weight (kg), and body mass index (kg/m2) 
by visit and treatment group.
All vital sign results will be listed.
9.4.
Electrocardiograms
Descriptive summaries will be presented for ECG measures of PR interval (msec), RR interval 
correction methods), and HR. These summaries will be presented by visit and treatment group.
The frequency and percentage of participants with normal, clinically significant abnormal, and 
not clinically significant abnormal ECG results will be summarized for the Safety Population by 
treatment group and visit.
All ECG results will be listed.
9.5.
Physical Examination
Frequencies and percentages of participants with normal, clinically significant abnormal, and not 
clinically significant abnormal physical exam findings will be summarized within the following 
body systems: general appearance, eyes, oral mucosa, heart, lungs, abdomen (liver/spleen), 
kidneys, neurological, and other. The following visits will be included:


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Baseline, Day 3 (Visit 3), Day 7 (Visit 4), Day 14 (Visit 5), Day 21 (Visit 6), Day 28 (Visit 7), 
Day 42 (Visit 8), Day 56 (Visit 9), Day 70 (Visit 10), Day 98 (Visit 11), Day 126 (Visit 12), Day 
154 (Visit 13).
All physical exam results will be listed.
9.6.
Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is routinely used to quantify the severity of suicidal ideation and behavior. Both the 
ideation and behavior subscales are sensitive to change over time.
Two versions of the C-SSRS will be used in this study: the Screening version and the Since Last 
Visit version. The Screening version of the C-SSRS assesses lifetime suicidal ideation and 
behavior. The Since Last Visit version of the C-SSRS assesses suicidal thoughts or behaviors the 
participant may have had since the last time the C-SSRS was administered. 
At the screening visit, the C-SSRS Screening version will be administered. At all subsequent 
visits, the C-SSRS Since Last Visit version will be administered.
The C-
ehavior 
as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most 
severe).  Assign a score of 0 if no ideation is present.
Suicidal Ideation items include:
Category 1 Wish to be Dead
Category 2 Non-specific Active Suicidal Thoughts
Category 3 Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act
Category 4 Active Suicidal Ideation with Some Intent to Act, without Specific Plan
Category 5 Active Suicidal Ideation with Specific Plan and Intent
Suicidal Behavior items include:
Category 6 Preparatory Acts or Behavior
Category 7 Aborted Attempt
Category 8 Interrupted Attempt
Category 9 Actual Attempt (non-fatal)
Category 10 Completed Suicide
Self-injurious behavior without suicidal intent is also a C-SSRS outcome (although not suicide-
related) and has a binary response (yes/no).
Endpoints:
Composite endpoints based on the above categories are defined below:
Suicidal ideation
y one of the five 
suicidal ideation questions (Categories 1-5) on the C-SSRS.
Suicidal behavior
suicidal behavior questions (Categories 6-10) on the C-SSRS.


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Suicidal ideation or behavior: 
of the ten suicidal ideation and behavior questions (Categories 1-10) on the C-SSRS.
Baseline is defined as the most severe ideation and behavior reported in the past 6 months prior 
to the first dose of study drug. Suicidality data collected on the C-SSRS will be listed for all 
participants with at least one occurrence of suicidal ideation or behavior during treatment. Tables 
will include results from the Suicidal Ideation and Suicidal Behavior sections of the C-SSRS.  
Frequencies and percentages of participants
study visit on the Suicidal Ideation and Suicidal Behavior items will be summarized by treatment 
received.  
Additionally, shifts of whether participants experienced suicidal ideation, behavior, or both from 
pre-treatment to post-treatment will be summarized in a shift table. An additional shift table of 
maximum ideation from pre-treatment to post-treatment will also be provided.
All C-SSRS data will be listed.
9.7.
Prior and Concomitant Medications
Medications used in the study will be summarized as follows:
Medications that started prior to the first dose of study drug will be considered prior 
medications whether they were stopped prior to the first dose of study drug. 
Any medications continuing or starting post the first dose of study drug will be 
concomitant. 
If a medication starts prior to the first dose and continues after the first dose of study 
drug, it will be considered both prior and concomitant.
Summaries of medications and therapies will be presented in tabular form using the Therapeutic 
Indication (ATC level 3) as an upper classification and the preferred drug name as a lower 
classification level. All medications will be summarized by the number and percentage of 
participants taking each medication and sorted by descending counts (overall) in the upper 
classification term and the lower classification term within the upper. For each participant, the 
medication will be counted only once within the upper classification level and only once within 
the lower classification level. 
Prior and concomitant medication listings will include start and stop dates, medication name, 
route, dose, dose frequency, and reason for use.
10.
Changes from Planned Analysis
Four additional analysis populations are defined in this SAP but are not defined in the study 
protocol: All Subjects Population, mITT Population, Completers Population, and PK Population. 
These analysis populations have been added to enable the summary of disposition, the primary 
analysis of efficacy data (mITT), a sensitivity analysis of efficacy data (Completers), and 
analysis of PK data (PK). The Per-Protocol Population, also not defined in the study protocol but 
included in V1.0 of the SAP, was removed.
The score for the number cancellation item was originally set up to be derived within the clinical 


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study database, however prior to database lock, an error was discovered in the derivation of this 
item score. This error subsequently impacts the derivation of the ADAS-13 total score, which 
was also originally set up to be derived within the clinical study database. As a result, both the 
number cancellation item score and the ADAS-13 total score will be re-derived in the ADaM  
datasets for analysis purposes. 
The Modified Hachinski total score and ADCS-ADL total score were originally calculated and 
entered into the study database by the sites. To ensure accuracy, it was decided to re-derive these
total scores in the ADaM dataset.
Composite z-score scales (Cognitive Composite score; Memory composite score; Attention 
composite score; Executive Function composite score) are added to efficacy endpoints and their 
derivation are included in Section 6.1.8.
11.
Other Planned Analysis
11.1.
Pharmacokinetic and Pharmacodynamic Analysis
Pharmacokinetic parameters such as CT1812 cerebrospinal fluid (CSF)/plasma concentration 
ratio, and CT1812 plasma concentrations will be summarized by treatment or treatment and visit 
where applicable using the PK Population. Analysis of pharmacodynamic parameters are 
detailed in Section 8.8 (Biomarker Changes).


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12.
References
1. US Federal Register. (1998) International Conference on Harmonization; Guidance on 
Statistical Principles for Clinical Trials. Department of Health and Human Services: Food 
and Drug Administration [Docket No. 97D-0174]. Federal Register Volume 63, Number 179, 
pages 49583-49598. September 16, 1998.
2. ASA. (2016) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April 2016. http://www.amstat.org/about/ethicalguidelines.cfm 
3. The Royal Statistical Society: Code of Conduct, 2014. 
http://www.rss.org.uk/Images/PDF/join-us/RSS-Code-of-Conduct-2014.pdf.