Clinical trial NCT05575076
Conditions: Alzheimer Disease
Sponsor: Cassava Sciences, Inc.
Start date: 2022-11-07; Completion date: 2025-01-31
Enrollment: 1081 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this open-label extension study is to assess long-term safety and tolerability of simufilam 100 mg in subjects who have completed the RETHINK-ALZ or REFOCUS-ALZ Phase 3 clinical trials.

Detailed description:
This is a multi-national, multi-center, fixed-dose, 52-week, open-label extension study. After completing participation in either RETHINK-ALZ (PTI-125-06) or REFOCUS-ALZ (PTI-125-07), subjects will have the option to participate in this study. After the subject provides consent and the Investigator confirms the subject satisfies both inclusion and exclusion criteria, the study drug will be administered at the research site on Study Day 1 and subsequent visits will be scheduled.

We anticipate up to 1600 subjects may enroll in this study. Approximately up to 150 clinical sites in the USA, Canada, South Korea, and Australia will have the option to participate in this collaborative research effort.

For subjects electing to participate, the clinical and laboratory assessments from the Week 76 (REFOCUS-ALZ) or Week 52 (RETHINK-ALZ) End-of-Treatment visit will serve as Baseline Visit assessments for the open-label study on Study Day 1. All subjects will return in 4 weeks and every 12 weeks thereafter for safety assessments. At all post-baseline visits, subjects will report any adverse events since their last visit. In addition to adverse event monitoring, safety will be evaluated at every visit by vital signs, brief examinations, clinical laboratory tests (biochemistry, hematology, and urinalysis) and the Columbia Suicide Severity Rating Scale (C-SSRS). Study drug use since the last visit will be assessed and a new bottle of study drug will be dispensed.

The emerging subject safety assessments will be monitored throughout the study by an independent Data Safety Monitoring Board (DSMB).

Arms: arm 1: simufilam 100 mg oral tablet, twice daily
Interventions: intervention 1: Simufilam
Intervention descriptions: intervention 1: simufilam 100 mg oral tablet, twice daily

Protocol documents:
Prot_000.pdf: 



































































































SAP_001.pdf: 
Final Version 1.0    |    22-Feb-2025
Page 1 of 20
   Statistical Analysis Plan
Sponsor
Cassava Sciences, Inc.
Protocol Title:
An Open-Label, Long-Term Extension Study to Evaluate the 
Safety and Tolerability of Simufilam 100 mg Tablets in 
Participants with Mild to Moderate Alzheimer’s Disease
Protocol Number:
PTI-125-10
Premier Research PCN:
CASA231381
Document Version:
Final, Version 1.0
Document Date: 
22-Feb-2025


Statistical Analysis Plan, 
Sponsor Cassava Sciences, Inc.
Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
Page 2 of 20
Approvals
Role
Signatures
Premier Research
Print Name: Brandy Moon, PhD
                    Manager, Biostatistics
Sign Name:
Premier Research
Print Name: Christopher Olson, MSc
                    Sr. Principal Biostatistician
Sign Name:
Cassava Sciences, 
Inc.
Print Name: James W. Kupiec, MD
                  Chief Medical Officer
Sign Name:


Statistical Analysis Plan, 
Sponsor Cassava Sciences, Inc.
Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
Page 3 of 20
Document History
SAP Version
Approval Date
Change
Rationale
0.1
Not applicable. 
First draft
0.2
Response to the 
sponsor’s comment on 
Draft version 0.1
Second draft
0.3
Response to sponsor’s 
comments on Draft 
Version 0.2.
Third draft
1.0
22-Feb-2025
Finalized draft.
Finalized version


Statistical Analysis Plan, 
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Protocol Number PTI-125-10
PCN Number CASA231381
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Page 4 of 20
Table of Contents
Approvals........................................................................................................................................ 2
Document History........................................................................................................................... 3
Table of Contents............................................................................................................................ 4
List of Tables .................................................................................................................................. 5
List of Abbreviations ...................................................................................................................... 6
1.
Overview............................................................................................................................. 8
2.
Study Objectives and Endpoints......................................................................................... 8
2.1.
Study Objectives ........................................................................................................... 8
2.1.1. Primary Objective ......................................................................................................... 8
2.2.
Study Endpoints............................................................................................................ 8
2.2.1. Safety Endpoints........................................................................................................... 8
3.
Overall Study Design and Plan........................................................................................... 9
3.1.
Overall Design .............................................................................................................. 9
3.2.
Sample Size and Power................................................................................................. 9
3.3.
Study Population........................................................................................................... 9
3.4.
Treatments Administered.............................................................................................. 9
3.5.
Method of Assigning Subjects to Treatment Groups.................................................... 9
3.6.
Blinding and Unblinding............................................................................................... 9
3.7.
Schedule of Events...................................................................................................... 10
4.
Statistical Analysis and Reporting.................................................................................... 10
4.1.
Introduction................................................................................................................. 10
4.2.
Interim Analysis and Data Monitoring ....................................................................... 11
5.
Analysis Populations......................................................................................................... 11
6.
General Issues for Statistical Analysis.............................................................................. 11
6.1.
Statistical Definitions and Algorithms........................................................................ 11
6.1.1. Baseline....................................................................................................................... 11
6.1.2. Adjustments for Covariates......................................................................................... 12
6.1.3. Multiple Comparisons................................................................................................. 12
6.1.4. Handling of Dropouts or Missing Data....................................................................... 12
6.1.5. Pooling of Sites........................................................................................................... 12
6.1.6. Data Adjustments/Handling/Conventions .................................................................. 12
7.
Study Patients/Subjects and Demographics...................................................................... 13
7.1.
Disposition of Patients/Subjects and Withdrawals ..................................................... 13
7.2.
Demographics and Other Baseline Characteristics..................................................... 14
7.3.
Exposure and Compliance .......................................................................................... 14
8.
Efficacy Analysis.............................................................................................................. 14


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Protocol Number PTI-125-10
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8.1.
Primary Efficacy Analysis .......................................................................................... 14
8.2.
Secondary Efficacy Analysis ...................................................................................... 14
9.
Safety and Tolerability Analysis....................................................................................... 14
9.1.
Adverse Events ........................................................................................................... 14
9.1.1. Severity of Adverse Events......................................................................................... 15
9.1.2. Relationship to Study Drug......................................................................................... 15
9.1.3. Serious Adverse Events .............................................................................................. 16
9.1.4. Summaries of Adverse Events.................................................................................... 16
10.
Changes from Planned Analyses ...................................................................................... 17
11.
References......................................................................................................................... 18
12.
Tables, Listings, and Figures ............................................................................................ 18
12.1.
Demographic Data Summary Tables and Figures ...................................................... 18
12.2.
Safety Data.................................................................................................................. 19
12.3.
Planned Listing Descriptions...................................................................................... 19
List of Tables
Table 1: Schedule of Events ......................................................................................................... 10
Table 2: Demographic Data Summary Tables and Figures.......................................................... 18
Table 3: Safety Data...................................................................................................................... 19
Table 4: Planned Listings.............................................................................................................. 19


Statistical Analysis Plan, 
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Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
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List of Abbreviations
Abbreviation
Definition
AE
adverse event
ASA
American Statistical Association
BID
twice daily
BMI
body mass index
CDISC
Clinical Data Interchange Standards Consortium
CRF
case report form
CSR
clinical study report
DSMB 
data safety monitoring board
ED
early discontinuation
EMA
European Medicines Agency
ET
early termination
FDA
Food and Drug Administration
GCP
good clinical practice
ICH
International Conference on Harmonization
MedDRA
medical dictionary for regulatory activities
PT
preferred term
RSS
Royal Statistical Society
SAE
serious adverse event
SAF
safety analysis set
SAP
statistical analysis plan


Statistical Analysis Plan, 
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Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
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Abbreviation
Definition
SD
standard deviation
SOC
system organ class
TEAE
treatment-emergent adverse event
TLF
table, listing and figure


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Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
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1.
Overview
This Statistical Analysis Plan (SAP) describes the planned analysis and reporting for Cassava 
Sciences, Inc. protocol number PTI-125-10 (An Open-Label, Long-Term Extension Study to 
Evaluate the Safety and Tolerability of Simufilam 100 mg Tablets in Participants with Mild to 
Moderate Alzheimer’s Disease), dated 10-Nov-2023 and protocol version 3.0. 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 Trials (ICH, 1998). 
All work planned and reported for this SAP will follow internationally accepted guidelines, 
published by the American Statistical Association (ASA, 2018) and the Royal Statistical Society
(RSS, 2014), 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. The SAP will be finalized and approved 
prior to locking of the study database.
This document does not include the details of the planned analyses for the external Data Safety 
Monitoring Board (DSMB). The schedule of planned analyses is described in the DSMB charter 
and separate shells for tables, listings, and figures (TLF) are prepared for the DSMB meetings.
2.
Study Objectives and Endpoints
2.1.
Study Objectives
2.1.1. Primary Objective
The primary objective of this study is to evaluate the long-term safety and tolerability of simufilam 
100 mg tablets in subjects who have completed one of the two double-blind simufilam phase 3 
studies.
2.2.
Study Endpoints
2.2.1. Safety Endpoints
The safety endpoints of this study include the following:
x
Incidence of adverse events (AEs) including treatment-emergent, serious, related to study 
drug, and leading to withdrawal along with AEs by severity and relationship to study drug.


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Protocol Number PTI-125-10
PCN Number CASA231381
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3.
Overall Study Design and Plan
3.1.
Overall Design
As background for the statistical methods presented below, this section provides an overview of 
the study design and plan of study execution. The protocol is the definitive reference for all matters 
discussed in what follows.
This is a multi-national, multi-center, fixed-dose, 52-week, open-label extension study to evaluate 
the long-term safety and tolerability of simufilam 100 mg tablets in subjects who have completed 
one of the two double blind simufilam phase 3 studies. Subjects from either of the two double-
blind simufilam phase 3 studies (PTI-125-06 or PTI-125-07) rollover into this open-label extension 
study, provided that all inclusion and none of the exclusion criteria are met.
Once participants enrolled in the study, visits to the research clinic will occur at Weeks 4, 16, 28, 
40 and 52. 
Safety will be evaluated by adverse event monitoring at every visit. 
An independent DSMB will meet periodically to review participant safety assessments and 
determine if dosing may continue. A charter was developed with specific guidance for the DSMB.
No interim analysis is planned for this study. 
3.2.
Sample Size and Power
As the PTI-125-10 study is primarily focused on long-term safety of simufilam from rollover 
studies PTI-125-06 and PTI-125-07, no formal sample size was calculated.
3.3.
Study Population
The study population is comprised of 1081 participants with mild-to-moderate AD. Participants 
are enrolled from approximately 141 clinical sites in the USA, Canada, the Republic of Korea, and 
Australia. For subjects electing to participate, the clinical and laboratory assessments from the 
Week 76 (PTI-125-06) or Week 52 (PTI-125-07) End-of-Treatment visit served as Baseline Visit 
assessments for the open-label study on Study Day 1. 
3.4.
Treatments Administered
All participants received simufilam 100 mg tablets BID.
3.5.
Method of Assigning Subjects to Treatment Groups
This is an open-label, non-randomized study. All the participants received simufilam 100 mg
tablets twice daily.
3.6.
Blinding and Unblinding
All participants, investigators, and study personnel are aware of the treatment assignment and 
receipt of study drug during the conduct of the study, through database lock.


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Protocol Number PTI-125-10
PCN Number CASA231381
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3.7.
Schedule of Events
Table 1: Schedule of Events
Procedures
Baseline 
Visit 
(Study 
Day 1)
Week 
4
Week 
16
Week 
28
Week 
40
Week 52 
ET/ED3
Week 
53 to 
54
Informed Consent
X
I/E Criteria
X
Adverse Events
X
X
X
X
X
X
X
Concomitant Meds
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
Brief Physical
Examination
X
X
X
X
X
X
Brief Neurologic 
Examination
X
X
X
X
X
X
Height
X
Weight
X
X
X
X
X
X
Resting ECG
X
X
X
X
Biochemistry, 
Hematology, 
Urinalysis
X
X
X
X
HbA1c3
X
X4
X4
C-SSRS1
X
X
X
X
X
X
Drug Dispensation
X2
X
X
X
X
Drug Accountability
X
X
X
X
X
End of Study Follow-
up Phone Call
X
1.
On Study Day 1, as well as all remaining visits, the ‘C-SSRS Since Last Visit’ version will be
administered.
2.
The first dose of study drug is administered at the clinic to all subjects on Study
Day 1 at least four hours after any prior dose and at least one hour before 
departure.
3.
HbA1c collection will begin upon receipt of required supplies. 
4.
Week 28 and Week 52 HbA1c should only be collected in subjects with a Day 1 HbA1c. 
4.
Statistical Analysis and Reporting
4.1.
Introduction
Data processing, tabulation of descriptive statistics, calculation of inferential statistics, and 
graphical representations will primarily use SAS (release 9.4 or higher). If the use of other software 


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Protocol Number PTI-125-10
PCN Number CASA231381
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is warranted, the final statistical methodology report will detail what software was used for what 
purposes.
Descriptive summaries of variables will be provided where appropriate. Continuous (quantitative) 
variable summaries will include the number of subjects (n) with non-missing values, mean, 
standard deviation (SD), median, minimum, and maximum.
Categorical (qualitative) variable summaries will include the frequency and percentage of subjects 
who are in the category for each value. In general, the denominator for the percentage calculation 
will be based upon the total number of subjects in the study population for the treatment group (or 
cohorts), unless otherwise specified. 
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 and 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.
This study is considered an exploratory study. Statistical tests will be interpreted in an exploratory 
sense only and will not be considered formal hypothesis tests.
4.2.
Interim Analysis and Data Monitoring
No interim analyses are planned.
An external DSMB will be involved in the management of this study. The DSMB meeting will be 
held periodically for the duration of the study. The purpose of the DSMB is to review the progress 
of the study with special regard to safety and make recommendations to the Sponsor on how to 
handle any safety concerns that arise. Further details regarding the DSMB can be found in the 
DSMB charter which was finalized before the first meeting was scheduled.
5.
Analysis Populations
The following analysis populations are planned for this study: 
x
Safety Population (SAF): The SAF analysis set includes all participants who received at 
least one dose of study treatment. This population will be used for all safety analysis.
6.
General Issues for Statistical Analysis
6.1.
Statistical Definitions and Algorithms
6.1.1. Baseline
The last observation recorded before the first dose of treatment will be used as the baseline 
observation. The clinical and laboratory assessments performed at the Week 76 (PTI-125-06) or 
Week 52 (PTI-125-07) End-of-Treatment visit will serve as the baseline (Study Day 1) for this 
open-label extension study. In the event the End-of-Treatment visit and the Study Day 1 visit for 
the open-label extension study did not occur on the same date, the Medical Monitor was 
responsible for deciding whether any clinical and laboratory assessments needed to be repeated to 


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PCN Number CASA231381
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serve as baseline values for Study Day 1 depending upon the length of time between the two visits.
6.1.2. Adjustments for Covariates
No covariates are planned for this study.
6.1.3. Multiple Comparisons
No multiple comparisons are planned for this study.
6.1.4. Handling of Dropouts or Missing Data
Although every attempt will be made to ensure participants remain in the study to completion and 
all data is collected as scheduled, the occurrence of missing data cannot be completely prevented.
An incomplete start or stop date of an AE will be imputed as described in section 6.1.8.
Any participant who withdraws from the study will be considered to have missing data at all 
subsequent visits.
6.1.5. Pooling of Sites
No pooling of study centers is planned for this study.
6.1.6. Data Adjustments/Handling/Conventions
Only limited data required for analysis will be presented in listings or Clinical Data Interchange 
Standards Consortium (CDISC) datasets. Analysis results will be presented and summarized in 
either tables and/or listings. Data not subject to analysis according to this plan will not appear in 
any tables and listings.
The version 24.0 of the Medical Dictionary for Regulatory Activities (MedDRA) will be used to 
classify all AEs by system organ class (SOC) and preferred term (PT).
Ongoing AEs from the pivotal studies will be classified as TEAEs in the current study only if they 
increase in severity on or after the date of the first dose of study drug in the current study. 
Otherwise, they will be classified as medical history events.
Adverse events with entirely missing start dates will be classified as treatment-emergent, as 
appropriate.
For partial AE start dates: (a) if only the day is missing, and the month and year match the first 
dose date and the end date is on or after the first dose date, or AE is ongoing, then the date is 
assigned the first dose date thus the event will be considered as treatment-emergent; if the month 
and/or year do not match the first dose date or the end date is prior to the first dose date, then the 
day is assigned the first day of the month (01); (b) if month or the day and month are missing, and 
the year matches the first dose date and the end date is on or after the first dose date, or AE is 
ongoing, then the date is assigned the first dose date; if the year does not match the first dose date 


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Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
Page 13 of 20
or the end date is prior to the first dose date, then the day/month are assigned the first day of the 
year (01JAN).
For partial end dates: (a) if only the day is missing, then the day is assigned the last day of the 
month; (b) if both day and month are missing, they are assigned the last day of the year (31DEC).
Participants will be analyzed by the treatment received for all safety and tolerability assessments.
A treatment related AE is any AE with a relationship to the study drug of “Possibly Related” or 
“Probably Related” or “Reasonable Possibility”.
If partial dates occur, the convention for replacing missing dates for the purpose of statistical 
analysis is as follows: if just day is missing then the day assigned is the first day of the month or 
the date of first dose (if in the same month), whichever is later; if just month is missing then the 
month assigned is the month of the first dose, unless that results in a date before the first dose in 
which case the month after the first dose is used; and if both month and day are missing then the 
month assigned is the month of the first dose and the day assigned is either the first day of the 
month or the first dose date, whichever is later.
If partial times occur, the convention is as follows: if the missing time occurs on the day of the 
first dose and both the hour and minute are missing then the time assigned is the time of the first 
dose, otherwise if both the hour and minute are missing and the date is not the date of first dose 
the time assigned is 12:00; if the date is the same as the date of the first dose and only hour is 
missing the hour assigned is 12 or the hour of first dose, whichever is later, and if the date is the 
same as the date of first dose and only the minute is missing the minute assigned is 30 or the minute 
of first dose, whichever is later. Otherwise, the hour assigned is 12 if the hour is missing and the 
date is not the same as the date of first dose and the minute assigned is 30 is the date is not the 
same as the date of first dose.
These conventions will be applied only to adverse event onset dates and times with the following 
precaution: if the missing date and time reflect the date and time of onset of an adverse event, the 
modified date and time will be constructed to match the first documented date/time post drug 
administration while preserving the order in which the AE was reported in the CRF.
7.
Study Patients/Subjects and Demographics
7.1.
Disposition of Patients/Subjects and Withdrawals
A summary of the analysis sets includes the number and percentage of subject’s rollover and in 
the safety population. All percentages will be based on the safety population.
The following will be summarized by treatment group:
x
Number of participants who enrolled,
x
Number and percentage of participants in safety analysis set,
x
Number and percentage of participants who completed the study, and
x
Number and percentage of participants who discontinued from the study, including the reason 
for study discontinuation.


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Protocol Number PTI-125-10
PCN Number CASA231381
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7.2.
Demographics and Other Baseline Characteristics
Demographic and baseline characteristics [age, sex (including child-bearing potential for women), 
methods of contraception, race, ethnicity, weight, height, body mass index (BMI), and education 
level] will be summarized by treatment group using the descriptive statistics. 
Height and weight will be measured at Study Day 1 and then the BMI will be calculated at Study 
Day 1. If height is missing in Study Day 1 then the pivotal studies screening visit height and Study 
Day 1 weight will be used for BMI calculation. Individual subject demographics and baseline 
characteristics will be provided in listings. 
For the continuous variables, the number of non-missing values and the mean, standard deviation, 
minimum, median and maximum will be tabulated. 
For the categorical variables, the count and percentage of each value will be tabulated. 
These analyses will be conducted for the Safety populations.
7.3.
Exposure and Compliance
8.
Efficacy Analysis
8.1.
Primary Efficacy Analysis
No applicable Primary Efficacy Analysis is planned.
8.2.
Secondary Efficacy Analysis
No applicable Secondary Efficacy Analysis is planned. 
9.
Safety and Tolerability Analysis
All safety analyses will be performed on the safety analysis set.
Safety will be evaluated from reported AEs. No inferential statistical tests will be performed, 
unless otherwise specified. 
For all safety and tolerability analyses, participants will be analyzed by the actual treatment.
All safety and tolerability data will be presented in listings. 
9.1.
Adverse Events
An AE is any undesirable event that occurs to a participant during a study, whether that event is 
considered related to Study Drug.
All summaries of AEs will be based on treatment-emergent adverse events (TEAEs) unless 
specified otherwise.
An adverse event is considered a TEAE if:
x
The adverse event first occurred on or after the date of the first dose of study drug; or


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Protocol Number PTI-125-10
PCN Number CASA231381
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x
The adverse event was before the date of the first dose of study drug, but it increased in severity 
or became serious on or after the date of the first dose of study drug.
9.1.1. Severity of Adverse Events
The severity of each AE should be characterized and then classified into one of three clearly 
defined categories as follows:
x
Mild
x
Moderate
x
Severe
These three categories are based on the Investigator's clinical judgment, which in turn depends on 
consideration of several factors such as the participant's report and the physician's observations.
The missing severity of an AE will be imputed to “severe”.
9.1.2. Relationship to Study Drug
The relationship of each AE to the Study Drug will be based on the Investigator’s assessment as 
to whether there is a reasonable possibility the AE was caused by the Study Drug.
The causal relationship between an AE and the study drug will be categorized as two cases in the 
CRFs as follows:
Case 1: 
x
Unlikely Related,
x
Possibly Related, and
x
Probably Related.
The missing relationship to study drug of an AE will be imputed to “Probably Related”.
Treatment-related TEAEs are defined as the TEAEs with relationship to study drug is “Possibly 
Related” or “Probably Related”.
Case 2: 
x
Not Related, and
x
Reasonable Possibility.
The missing relationship to study drug of an AE will be imputed to “Reasonable Possibility”.


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Treatment-related TEAEs are defined as the TEAEs with relationship to study drug is “Reasonable 
Possibility”.
For the analysis purposes (regardless of protocol amendment version), treatment-related TEAEs 
are defined as the TEAEs with relationship to study drug is “Possibly Related” or “Probably 
Related” or “Reasonable Possibility”.
9.1.3. Serious Adverse Events
A Serious Adverse Event (SAE) includes (but is not limited to) an experience occurring at any 
dose that results in any of the following outcomes:
x
Death,
x
Life-threatening,
x
In-patient hospitalization,
x
A persistent or significant disability/incapacity,
x
A congenital anomaly/birth defect, and
x
Other medically important event
9.1.4. Summaries of Adverse Events
An overall summary of TEAEs will be provided by treatment. This summary will present number 
and percentage of participants with TEAEs per the following classifications:
x
Participants with any TEAEs
x
Participants with Treatment-Emergent Drug-Related AEs
x
Participants with Treatment-Emergent AEs by Maximum Severity as Mild, 
Moderate, and Severe.
x
Participants with TEAE leading to discontinuation from study
x
Participants with Treatment-Emergent SAEs
x
Participants with Treatment-Emergent SAEs leading to discontinuation from 
study
x
Participants with Treatment-Emergent SAEs resulting in death
The following summary tables for TEAEs will be presented:


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x
Number and percent of participants reporting treatment-emergent AEs, grouped 
by MedDRA system organ class and preferred term
x
Number and percent of participants reporting treatment-emergent drug-related 
AEs, grouped by MedDRA system organ class, and preferred term
x
Number and percent of participants reporting treatment-emergent AEs, grouped 
by MedDRA system organ class, preferred term, and maximum severity
x
Number and percent of participants reporting treatment-emergent SAEs will be 
tabulated by system organ class and preferred term and presented by treatment.
x
Number and percent of participants reporting treatment-emergent AEs leading 
to study discontinuation, grouped by MedDRA system organ class and preferred 
term
For the summary tables above, the SOC terms and PTs will be presented in decreasing order of the 
total number of participants (frequency) who experienced each AE. System organ class terms and 
PTs with the same frequency will be presented alphabetically. In the case of multiple occurrences 
of the same TEAE within the same participant, each participant will only be counted once for each 
preferred term.
The following data listings for AEs will be provided for each participant by displaying the events 
captured on the CRF:
x
All AEs,
x
All serious AEs,
x
All AEs leading to study discontinuation, and
x
All AEs leading to Death.
In the AE data listings, all AEs will be displayed. AEs that are not treatment-emergent will be 
flagged in the AE listings.
10.
Changes from Planned Analyses
Due to the early sponsor termination of PTI-125-10, the following analyses will no longer be 
tabulated/listed:
x
Mean change in clinical laboratory values from baseline to Weeks 4, 28 and 52 
x
Mean change in vital signs (blood pressure [supine], temperature, pulse rate) 
from baseline to Weeks 4, 16, 28, 40, and 52
x
Mean change in body weight from baseline to Weeks 4, 16, 28, 40, and 52


Statistical Analysis Plan, 
Sponsor Cassava Sciences, Inc.
Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
Page 18 of 20
x
Shifts in physical exam (PE) findings from baseline to Weeks 4, 16, 28, 40, and 
52
x
Shifts in neurological exam (NE) findings from baseline to Week 4, 16, 28, 40, 
and 52
x
Mean change in ECG parameters from baseline to Weeks 4, 28, and 52
x
Concomitant medications/treatments usage
x
Shifts in the C-SSRS from baseline to Weeks 4, 16, 28, 40, and 52.
x
Shifts in HbA1c values from baseline to Weeks 28 and Week 52. The analysis 
is done separately among subjects who were previously on placebo and 
simufilam in PTI-125-06 and PTI-125-07 phase 3 studies.
11.
References
1. Protocol number PTI-125-10, An Open-Label, Long-Term Extension Study to Evaluate 
the Safety and Tolerability of Simufilam 100 mg Tablets in Participants with Mild to 
Moderate Alzheimer’s Disease, dated 10-NOV-2023 (version 3.0). 
2. ASA. (2018) Ethical Guidelines for Statistical Practice. Prepared by the Committee on 
Professional Ethics, April 2018. http://www.amstat.org/about/ethicalguidelines.cfm
3. ICH (1998). ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials 
E9; 1998. https://database.ich.org/sites/default/files/E9_Guideline.pdf
4. RSS. 
(2014) 
The 
Royal 
Statistical 
Society: 
Code 
of 
Conduct, 
2014.
https://rss.org.uk/about/policy-and-guidelines/code-of-conduct/.
12.
Tables, Listings, and Figures
All listings, tables, and graphs will have a header showing the sponsor company name and protocol 
and a footer showing the version of SAS, the file name and path, and the source of the data (CRF 
page or listing number).
The following are planned summary tables for protocol number PTI-125-10. The table numbers 
and page numbers are place holders only and will be determined when the tables are produced.
12.1.
Demographic Data Summary Tables and Figures
Table 2: Demographic Data Summary Tables and Figures
Table Number
Population
Table Title/Summary
Table 14.1.1
Safety
Subject Disposition (Includes All Early Terminations)
Table 14.1.2
Safety
Demographics and Baseline Characteristics


Statistical Analysis Plan, 
Sponsor Cassava Sciences, Inc.
Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
Page 19 of 20
12.2.
Safety Data
Table 3: Safety Data
Table Number
Population
Table Title / Summary
14.3.1 Displays of Adverse Events
Table 14.3.1.1
Safety
Overall Summary of Treatment Emergent Adverse Events
Table 14.3.1.2
Safety
Summary of Treatment Emergent Adverse Events by System Organ 
Class and Preferred Term
Table 14.3.1.3
Safety
Summary of Treatment Emergent Drug-Related Adverse Events by 
System Organ Class and Preferred Term
Table 14.3.1.4
Safety
Summary of Treatment Emergent Adverse Events by System Organ 
Class, Preferred Term, and Maximum Severity
Table 14.3.1.5
Safety
Summary of Serious Treatment Emergent Adverse Events by System 
Organ Class and Preferred Term
Table 14.3.1.6
Safety
Summary of Treatment Emergent Adverse Events Leading to Study 
Discontinuation by System Organ Class and Preferred Term
14.3.2 Summary of Deaths, Other Serious and Significant Adverse Events
Table 14.3.2.1
Safety
Listing of Serious Adverse Events
Table 14.3.2.2
Safety
Listing of Adverse Events Leading to Study Discontinuation
Table 14.3.2.3
Safety
Listing of Adverse Events Leading to Death
12.3.
Planned Listing Descriptions
The following are planned data and patient/subject data listings for protocol number PTI-125-10.
In general, one listing will be produced per CRF domain. All listings will be sorted by treatment, 
site, and subject number. All calculated variables will be included in the listings.
In all listings a blank line will be placed between each subject. Within a data listing, if an item 
appears line after line (e.g., repetition of subject number), then only the first occurrence will be 
displayed.
In data listings, the information for one subject will be kept on one page, if at all possible, rather 
than splitting a subject’s information across pages.
Table 4: Planned Listings
Data Listing Number
Population
Data Listing Title / Summary
16.2 Subject Data Listings
16.2.1 Subject Discontinuations/Completions
Data Listing 16.2.1.1
Safety
Subject Disposition
16.2.4 Demographic Data and Other Baseline Characteristics


Statistical Analysis Plan, 
Sponsor Cassava Sciences, Inc.
Protocol Number PTI-125-10
PCN Number CASA231381
Final Version 1.0    |    22-Feb-2025    
Page 20 of 20
Data Listing Number
Population
Data Listing Title / Summary
16.2 Subject Data Listings
Data Listing 16.2.4.1
Safety
Demographic and Baseline Characteristics
16.2.7 Adverse Event Listings (by Patient/Subject)
Data Listing 16.2.7.1
Safety
Treatment Emergent Adverse Events