Simufilam 50 mg or 100 mg for Mild-to-Moderate Alzheimer'... | NCT05026177

Status Module

Name	Class
Premier Research	OTHER

Description Module

Detailed Description

The primary objective of this study is to investigate the safety and efficacy of simufilam (PTI-125) in enhancing cognition and slowing cognitive and functional decline following 76-week, repeat-dose oral administration in participants with mild-to-moderate AD. Secondary objectives are to assess neuropsychiatric symptoms and to replicate the cerebrospinal fluid (CSF) biomarker effects observed in the two Phase 2 studies (PTI-125-03 and PTI-125-02) after 76 weeks of simufilam treatment. A third objective is to investigate the effect of simufilam treatment on plasma biomarkers as well as anatomical correlates of disease progression (brain volume [hippocampus, ventricles and whole brain]; and amyloid and tau deposition in the brain). A limited number of research sites will be invited to participate in sub-studies to assess the impact of simufilam on anatomical and biomarker endpoints, including: change from Baseline in CSF biomarkers (30 subjects/group); brain volume via magnetic resonance imaging (MRI) (50 subjects/group); and amyloid and tau positron emission tomography (PET) (40 and 50 subjects/group, respectively). Participants in both PET sub-studies will be required to have an MRI during the Screening Period and provide plasma for a biomarker sub-study. Participants in the tau PET sub-study will also provide additional plasma for a pharmacokinetic (PK) exposure response analysis. Changes from baseline for these imaging and fluid biomarkers represent additional secondary endpoints. The 90 subjects (30 per group) in the CSF sub-study will undergo lumbar puncture during the Screening Period and again at the Week 76 End-of-Treatment Visit to collect CSF biomarkers.

Safety will be evaluated by adverse event monitoring, vital signs, clinical labs, and the Columbia Suicide Severity Rating Scale at every visit. Subjects will undergo MRI during screening to ensure entry criteria are met (unless recent MRI confirms entry criteria); however, 150 subjects (50 subjects per treatment group) will also undergo repeat MRI assessments at Weeks 40 and 76 to assess both long-term safety and drug impact on brain volume as noted above. Resting electrocardiograms will be conducted at Baseline (Study Day 1) and Weeks 4, 40 and 76. A complete physical and neurological examination will be performed at screening, and brief examinations will be performed at all other visits. Weight will be measured during the Screening Period, at Baseline (Study Day 1) and at all other visits.

An independent Data Safety Monitoring Board (DSMB) will meet periodically to review subject safety assessments and determine if dosing may continue. A charter will be developed with specific guidance for the DSMB.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 76 weeks	Drug: Placebo
Simufilam 50 mg	Experimental	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks	Drug: Simufilam
Simufilam 100 mg	Experimental	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks	Drug: Simufilam

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Simufilam	Drug	Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)	The change from baseline to Week 76 in the ADAS-Cog12, a psychometrician-administered battery comprised of several cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Scores range from 0 (best) to 80 (worst).	Baseline (Study Day 1) to Week 76
Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)	The change from baseline to Week 76 in the ADCS-ADL, a 23-item study partner questionnaire that covers both basic activities of daily living (ADL) and more complex ADL or instrumental ADL for the subject. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.	Baseline (Study Day 1) to Week 76

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)	The change from baseline to Week 76 in the iADRS, where scores range from 0 to 146 with lower scores indicating worse performance.	Baseline (Study Day 1) to Week 76
Change From Baseline in the Neuropsychiatric Inventory (NPI)

Other Outcomes

Measure	Description	Time Frame
Changes From Baseline in Brain Volume Via MRI	Changes from baseline in hippocampus, ventricles, and whole brain volume.	Baseline (Study Day 1) to Week 76
Changes From Baseline in Amyloid Positron Emission Tomography (PET)

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria:

Meets National Institute on Aging and Alzheimer's Association Research Framework criteria for individuals in clinical Stage 4 or 5 of the Alzheimer's continuum.
Evidence for AD pathophysiology, confirmed prior to or during screening.
MMSE score ≥ 16 and ≤ 27 at screening.
Clinical Dementia Rating - Global Score must be 0.5, 1 or 2.
If receiving background AD medications, the dosing regimen must be stable for at least 12 weeks prior to randomization. Chronic medications for conditions other than AD (such as depression) must be prescribed at a stable dose for at least 4 weeks prior to screening.
The subject has not been a cigarette smoker or chewed tobacco for at least 3 years.
Availability of a study partner.
Individuals who have participated in a clinical study with an investigational drug targeting the underlying AD process may be permitted to participate in this study.
Completed a COVID-19 vaccine primary series ("fully vaccinated") at least 2 weeks prior to randomization or had an unambiguous COVID-19 infection diagnosed more than 3 months before the start of the Screening Period.

Key Exclusion Criteria:

A neurologic condition other than AD that significantly contributes to the subject's dementia.
Any current primary psychiatric diagnosis other than AD if it is likely to confound cognitive assessment or ability to comply with study procedures.
Geriatric Depression Scale (15-item) score > 8 (Note - a subject with a score > 8 may continue in screening if, in the judgment of the Investigator, the elevated score is not attributed to a major depressive episode).
Suicidal ideation during the past 3 months or suicidal behavior during the past 12 months.
Alcohol or substance use disorder within 2 years of screening.
MRI presence of cerebral vascular or other significant pathology.
History of transient ischemic attack or stroke within 12 months of screening.
Seizure within 12 months of screening.
Severe head trauma or head trauma considered likely to be contributing to the subject's cognitive impairment.
Sleep apnea that is considered likely to be contributing to the subject's cognitive impairment.
Insufficiently controlled diabetes mellitus or hypertension.
Body mass index < 18.5 or > 37.5.
History or diagnosis of clinically significant cardiac disease.
Currently or previously prescribed/administered aducanumab, lecanemab, or any anti-amyloid monoclonal antibody, more than 2 doses.

Name	Affiliation	Role
James Kupiec, MD	Cassava Sciences	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Banner Alzheimer's Institute		Phoenix	Arizona	85006	United States
Arizona Neuroscience Research, LLC

PubMed Identifier	Type	Citation	Retractions
41500915	Derived	Kupiec JW, Porsteinsson AP, Turner RS, Hendrix S, Mallinckrodt C, Khan A, Cohen I, Liss J, Clarnette R, Park KH, Hernandez AM, Burns LH. Phase 3 randomized clinical trials of simufilam in mild-to-moderate Alzheimer's disease. J Prev Alzheimers Dis. 2026 Mar;13(3):100469. doi: 10.1016/j.tjpad.2025.100469. Epub 2026 Jan 6.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 7, 2024	Jul 23, 2025

Arm/Group Information

ID	Title	Description
BG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
BG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
BG002	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 76 weeks Placebo: Matching placebo given b.i.d. for 76 weeks
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00074.45± 7.624 BG00173.64± 8.185 BG00273.72± 7.926 BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

<65 years

Title	Measurements
	BG00047 BG00154 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000207 BG001208 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00027 BG00135 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Canada

Title	Measurements
	BG00046 BG00147 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)

The change from baseline to Week 76 in the ADAS-Cog12, a psychometrician-administered battery comprised of several cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Scores range from 0 (best) to 80 (worst).

Data are from subjects in the modified intent-to-treat population (all randomized subjects with baseline plasma P-tau181 ≥44 pg/mL or other evidence of amyloid pathology, e.g., amyloid PET) who completed the assessment. No data were collected from study partners for this outcome measure.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG002	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 76 weeks Placebo: Matching placebo given b.i.d. for 76 weeks

Units	Counts
Participants	OG000167 OG001181 OG002188

Title

Denominators

Categories

Title	Measurements
	OG0005.71± 0.529 OG0015.65± 0.509 OG0025.26± 0.506

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		Mixed Models Analysis		0.5335		Mean Difference (Final Values)	0.45			2-Sided	95	-0.96	1.86					Superiority
OG001 OG002		Mixed Models Analysis		0.5836

Primary

Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

The change from baseline to Week 76 in the ADCS-ADL, a 23-item study partner questionnaire that covers both basic activities of daily living (ADL) and more complex ADL or instrumental ADL for the subject. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Secondary

Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)

The change from baseline to Week 76 in the iADRS, where scores range from 0 to 146 with lower scores indicating worse performance.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Secondary

Change From Baseline in the Neuropsychiatric Inventory (NPI)

The change from baseline to Week 76 in the NPI, a 12-item study partner interview, which records the frequency and severity of common neuropsychiatric symptoms in dementia for the subject, as well as the level of study partner distress due to the neuropsychiatric problems. Scores range from 0 to 144, with higher scores indicating more frequent and severe symptoms, and greater levels of partner distress.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Secondary

Change From Baseline in the MMSE

The change from baseline to Week 76 in the MMSE, a set of standardized questions covering several target areas: orientation, registration, attention and calculation, short-term verbal recall, naming, repetition, 3-step command, reading, writing, and visuospatial cognitive assessment. Scores range from 0 to 30; lower scores indicate more severe impairment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Secondary

Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)

The change from baseline to Week 76 in the CDR-SB, which characterizes 6 domains of cognitive and functional performance applicable to AD and related dementias: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Scores for each domain have a minimum of 0 and a maximum of 3, and the 6 domain scores are summed to give the CDR-SB, which has a minimum score of 0 and a maximum score of 18. Higher scores indicate more severe impairment.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg

Secondary

Change From Baseline in the Zarit Burden Interview (ZBI)

The change from baseline to Week 76 in the ZBI, a 22-item study partner questionnaire designed to assess the stress or burden experienced by caregivers of people with dementia. Scores range from 0 to 88, with a higher score indicating greater stress or burden.

Data are from the study partners of subjects in the modified intent-to-treat population (all randomized subjects with baseline plasma P-tau181 ≥44 pg/mL or other evidence of amyloid pathology, e.g., amyloid PET) who completed the assessment. No data were collected from study partners for this outcome measure.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Other Pre-specified

Changes From Baseline in Brain Volume Via MRI

Changes from baseline in hippocampus, ventricles, and whole brain volume.

The overall number of subjects analyzed is the number of subjects who consented to take part in the MRI imaging substudy and for whom there was at least one non-missing post baseline MRI assessment available. MRIs were not conducted in the whole substudy population at Week 76. No data were collected from study partners for this outcome measure.

Posted

Mean

Standard Deviation

µL

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Other Pre-specified

Changes From Baseline in Amyloid Positron Emission Tomography (PET)

Changes from baseline in amyloid deposition in the brain.

The overall number of subjects analyzed is the number of subjects who consented to take part in the amyloid PET imaging substudy and for whom there were baseline and Week 76 values. No data were collected from study partners for this outcome measure.

Posted

Mean

Standard Deviation

µL

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Other Pre-specified

Changes From Baseline in Tau Positron Emission Tomography (PET)

Changes from baseline in tau deposition in the brain

The overall number of subjects analyzed is the number of subjects who consented to take part in the tau PET imaging substudy and for whom there were baseline and Week 76 values. No data were collected from study partners for this outcome measure.

Posted

Least Squares Mean

Standard Error

µL

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Other Pre-specified

Changes From Baseline in Plasma Biomarkers

Change from baseline in the following plasma biomarkers of AD pathology, neurodegeneration, and neuroinflammation: phospho-tau217 (P-tau217), total tau, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL).

The overall number of subjects analyzed is the number of subjects who consented to take part in the plasma biomarker analysis substudy and for whom there were baseline and Week 76 values for each biomarker. Plasma samples were not obtained from the whole substudy population at Week 76. No data were collected from study partners for this outcome measure.

Posted

Mean

Standard Deviation

pg/mL

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Other Pre-specified

Changes From Baseline in CSF Biomarkers

Changes from baseline in CSF biomarkers of AD pathology, neurodegeneration, and neuroinflammation: P-tau217, total tau, GFAP, and NfL.

The overall number of subjects analyzed is the number of subjects who consented to take part in the CSF biomarker analysis substudy and for whom there were baseline and Week 76 values for each biomarker. CSF samples were not obtained from the whole substudy population at Week 76. No data were collected from study partners for this outcome measure.

Posted

Mean

Standard Deviation

pg/mL

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Other Pre-specified

Change From Baseline in Plasma Biomarker SavaDx

Change from baseline in SavaDx, a novel plasma biomarker.

Change from baseline in SavaDx, a novel plasma biomarker, was included in the protocol as part of the secondary analysis as a biomarker which may have been measured. The final SAP, which postdated the protocol, included the analysis of biomarkers as an exploratory/tertiary endpoint. However, analysis of SavaDx was not conducted due to a sponsor decision and therefore, no results are available.

Posted

Baseline (Study Day 1) to Week 76

ID	Title	Description
OG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.
OG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Simufilam 50 mg	Simufilam 50 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.	6	376	61	376	198	376
EG001	Simufilam 100 mg	Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 76 weeks Simufilam: Simufilam is a novel drug candidate designed to treat and slow the progression of AD. Simufilam binds with femtomolar affinity to an altered conformation of filamin A that is present in the brain of patients with AD and critical to the toxicity of Aβ42. In this study, simufilam will be given b.i.d. for 76 weeks at a dose of 50 mg or 100 mg.	2	374	43	374	184	374
EG002	Placebo	Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 76 weeks Placebo: Matching placebo given b.i.d. for 76 weeks	3	373	45	373	195	373

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fall	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0005 events5 affected376 at risk EG0011 events1 affected374 at risk EG0023 events3 affected373 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0003 events3 affected376 at risk EG0011 events1 affected374 at risk EG0022 events2 affected373 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Acetabulum fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0022 events2 affected373 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0012 events2 affected374 at risk EG0020 events0 affected373 at risk
Accidental poisoning	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Anaemia postoperative	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Fractured sacrum	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Sternal fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Traumatic intracranial haemorrhage	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Vascular graft occlusion	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0002 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Wrist fracture	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Syncope	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0004 events4 affected376 at risk EG0011 events1 affected374 at risk EG0022 events2 affected373 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0011 events1 affected374 at risk EG0023 events3 affected373 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0010 events0 affected374 at risk EG0022 events2 affected373 at risk
Dementia Alzheimer's type	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Presyncope	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Altered state of consciousness	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Brain stem stroke	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Cerebral infarction	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Cerebrospinal fluid leakage	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Dementia	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Dizziness	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Encephalopathy	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Generalised tonic-clonic seizure	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Hypoglycaemic encephalopathy	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Loss of consciousness	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Motor dysfunction	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Normal pressure hydrocephalus	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0012 events1 affected374 at risk EG0020 events0 affected373 at risk
Seizure	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
COVID-19	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0003 events3 affected376 at risk EG0012 events2 affected374 at risk EG0022 events2 affected373 at risk
Pneumonia	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0013 events3 affected374 at risk EG0022 events1 affected373 at risk
Urinary tract infection	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0004 events4 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Sepsis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0012 events2 affected374 at risk EG0021 events1 affected373 at risk
Diverticulitis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0022 events2 affected373 at risk
Appendicitis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Escherichia pyelonephritis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Gastroenteritis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Influenza	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Pulmonary sepsis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Pyelonephritis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Urosepsis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Atrial fibrillation	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0003 events2 affected376 at risk EG0011 events1 affected374 at risk EG0021 events1 affected373 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Cardiac arrest	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Angina pectoris	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Angina unstable	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Coronary artery disease	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Sinus bradycardia	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Tachycardia	Cardiac disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Colitis	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0021 events1 affected373 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0022 events1 affected373 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Dysphagia	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Functional gastrointestinal disorder	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Gastritis	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Incarcerated inguinal hernia	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Breast cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Chronic lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Metastatic malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Non-small cell lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0011 events1 affected374 at risk EG0022 events2 affected373 at risk
Haematuria	Renal and urinary disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Renal cyst	Renal and urinary disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Urethral perforation	Renal and urinary disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Urethral stenosis	Renal and urinary disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Urinary retention	Renal and urinary disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Pulmonary thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Respiratory alkalosis	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Asthenia	General disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0012 events2 affected374 at risk EG0021 events1 affected373 at risk
Chest pain	General disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0022 events2 affected373 at risk
Death	General disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
General physical health deterioration	General disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Mass	General disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Sudden death	General disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0022 events2 affected373 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Fracture pain	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Tenosynovitis	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0012 events2 affected374 at risk EG0020 events0 affected373 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Fluid overload	Metabolism and nutrition disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Blood glucose decreased	Investigations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Blood magnesium decreased	Investigations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Heart rate increased	Investigations	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Heart rate irregular	Investigations	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Troponin increased	Investigations	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Aggression	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG0002 events2 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Anxiety	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Delirium	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Psychotic disorder	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Deep vein thrombosis	Vascular disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0021 events1 affected373 at risk
Aortic occlusion	Vascular disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Shock haemorrhagic	Vascular disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Thrombosis	Vascular disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk
Splenic haemorrhage	Blood and lymphatic system disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0011 events1 affected374 at risk EG0020 events0 affected373 at risk
Vertigo	Ear and labyrinth disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Diplopia	Eye disorders	MedDRA, v24.0	Systematic Assessment	EG0000 events0 affected376 at risk EG0010 events0 affected374 at risk EG0021 events1 affected373 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA, v24.0	Systematic Assessment	EG0001 events1 affected376 at risk EG0010 events0 affected374 at risk EG0020 events0 affected373 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
COVID-19	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG00048 events47 affected376 at risk EG00143 events43 affected374 at risk EG00238 events38 affected373 at risk
Urinary tract infection	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG00047 events39 affected376 at risk EG00140 events32 affected374 at risk EG00243 events34 affected373 at risk
Nasopharyngitis	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0008 events7 affected376 at risk EG00111 events10 affected374 at risk EG00212 events9 affected373 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA, v24.0	Systematic Assessment	EG0009 events9 affected376 at risk EG0016 events6 affected374 at risk EG0028 events6 affected373 at risk
Dizziness	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG00011 events11 affected376 at risk EG00129 events26 affected374 at risk EG00225 events22 affected373 at risk
Headache	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG00022 events16 affected376 at risk EG00118 events17 affected374 at risk EG00215 events13 affected373 at risk
Syncope	Nervous system disorders	MedDRA, v24.0	Systematic Assessment	EG0004 events4 affected376 at risk EG0010 events0 affected374 at risk EG0027 events6 affected373 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG00019 events19 affected376 at risk EG00118 events14 affected374 at risk EG00217 events15 affected373 at risk
Nausea	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0009 events9 affected376 at risk EG00119 events13 affected374 at risk EG00215 events15 affected373 at risk
Constipation	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0007 events6 affected376 at risk EG00111 events11 affected374 at risk EG00211 events11 affected373 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0008 events8 affected376 at risk EG0014 events4 affected374 at risk EG0027 events7 affected373 at risk
Vomiting	Gastrointestinal disorders	MedDRA, v24.0	Systematic Assessment	EG0005 events5 affected376 at risk EG00112 events8 affected374 at risk EG0026 events6 affected373 at risk
Fall	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG00056 events40 affected376 at risk EG00150 events32 affected374 at risk EG00264 events48 affected373 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA, v24.0	Systematic Assessment	EG0008 events8 affected376 at risk EG0017 events6 affected374 at risk EG0025 events5 affected373 at risk
Anxiety	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG00014 events14 affected376 at risk EG00113 events13 affected374 at risk EG00213 events12 affected373 at risk
Depression	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG00012 events12 affected376 at risk EG0019 events9 affected374 at risk EG00216 events16 affected373 at risk
Agitation	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG00016 events16 affected376 at risk EG0017 events5 affected374 at risk EG00215 events14 affected373 at risk
Insomnia	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG0008 events8 affected376 at risk EG0018 events8 affected374 at risk EG0026 events6 affected373 at risk
Confusional state	Psychiatric disorders	MedDRA, v24.0	Systematic Assessment	EG0006 events6 affected376 at risk EG0018 events8 affected374 at risk EG0021 events1 affected373 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG00016 events14 affected376 at risk EG00112 events12 affected374 at risk EG00214 events13 affected373 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG00016 events16 affected376 at risk EG00113 events13 affected374 at risk EG00211 events9 affected373 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA, v24.0	Systematic Assessment	EG0009 events9 affected376 at risk EG0012 events2 affected374 at risk EG0023 events3 affected373 at risk
Weight decreased	Investigations	MedDRA, v24.0	Systematic Assessment	EG0006 events6 affected376 at risk EG00118 events17 affected374 at risk EG0028 events8 affected373 at risk
Fatigue	General disorders	MedDRA, v24.0	Systematic Assessment	EG00015 events15 affected376 at risk EG00116 events16 affected374 at risk EG00210 events10 affected373 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA, v24.0	Systematic Assessment	EG0009 events9 affected376 at risk EG0018 events8 affected374 at risk EG0024 events4 affected373 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA, v24.0	Systematic Assessment	EG0008 events8 affected376 at risk EG00110 events8 affected374 at risk EG00210 events7 affected373 at risk
Hypertension	Vascular disorders	MedDRA, v24.0	Systematic Assessment	EG00011 events11 affected376 at risk EG0015 events5 affected374 at risk EG00214 events14 affected373 at risk

ID	Term
D003704	Dementia
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D024801	Tauopathies
D019636	Neurodegenerative Diseases
D019965	Neurocognitive Disorders
D001523	Mental Disorders