Trial Outcomes & Findings for An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early AD Subjects (NCT NCT04770220)

Results Overview

Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-Cog13) scores. The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

325 participants

Primary outcome timeframe

Baseline to Week 78

Results posted on

2025-11-10

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Overall Study STARTED	162	163
Overall Study COMPLETED	148	132
Overall Study NOT COMPLETED	14	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Overall Study Adverse Event	2	11
Overall Study Withdrawal by Subject	5	11
Overall Study Lost to Follow-up	4	3
Overall Study not otherwise specified	2	3
Overall Study Physician Decision	1	3

Baseline Characteristics

Not all patients had all baseline measures taken/assessed/collected at baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=162 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=163 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID	Total n=325 Participants Total of all reporting groups
Age, Continuous	68.5 years STANDARD_DEVIATION 5.93 • n=162 Participants	68.4 years STANDARD_DEVIATION 6.36 • n=163 Participants	68.5 years STANDARD_DEVIATION 6.14 • n=325 Participants
Age, Customized 50 to <=65	46 Participants n=162 Participants	49 Participants n=163 Participants	95 Participants n=325 Participants
Age, Customized >65 to 80	116 Participants n=162 Participants	114 Participants n=163 Participants	230 Participants n=325 Participants
Sex: Female, Male Female	82 Participants n=162 Participants	85 Participants n=163 Participants	167 Participants n=325 Participants
Sex: Female, Male Male	80 Participants n=162 Participants	78 Participants n=163 Participants	158 Participants n=325 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=162 Participants	0 Participants n=163 Participants	0 Participants n=325 Participants
Race/Ethnicity, Customized Asian	1 Participants n=162 Participants	2 Participants n=163 Participants	3 Participants n=325 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=162 Participants	7 Participants n=163 Participants	13 Participants n=325 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=162 Participants	0 Participants n=163 Participants	0 Participants n=325 Participants
Race/Ethnicity, Customized White	145 Participants n=162 Participants	144 Participants n=163 Participants	289 Participants n=325 Participants
Race/Ethnicity, Customized Multiple Races	1 Participants n=162 Participants	1 Participants n=163 Participants	2 Participants n=325 Participants
Race/Ethnicity, Customized Race Not Reported/Missing	9 Participants n=162 Participants	9 Participants n=163 Participants	18 Participants n=325 Participants
Race/Ethnicity, Customized Hispanic/Latino	7 Participants n=162 Participants	5 Participants n=163 Participants	12 Participants n=325 Participants
Race/Ethnicity, Customized Not Hispanic/Latino	141 Participants n=162 Participants	147 Participants n=163 Participants	288 Participants n=325 Participants
Race/Ethnicity, Customized Ethnicity Not Reported	14 Participants n=162 Participants	11 Participants n=163 Participants	25 Participants n=325 Participants
Alzheimer's Diagnosis based on MMSE Mild cognitive impairment (MCI) MMSE 27-30	60 Participants n=162 Participants	67 Participants n=163 Participants	127 Participants n=325 Participants
Alzheimer's Diagnosis based on MMSE Mild Alzheimer's Disease (Mild AD) MMSE 22-26	102 Participants n=162 Participants	96 Participants n=163 Participants	198 Participants n=325 Participants
Concomitant AChEI Yes	62 Participants n=162 Participants	54 Participants n=163 Participants	116 Participants n=325 Participants
Concomitant AChEI No	100 Participants n=162 Participants	109 Participants n=163 Participants	209 Participants n=325 Participants
Baseline Clinical Outcomes Assessments (Safety Population) ADAS-Cog13	24.31 units on a scale STANDARD_DEVIATION 8.86 • n=162 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	23.554 units on a scale STANDARD_DEVIATION 8.26 • n=163 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	23.93 units on a scale STANDARD_DEVIATION 8.56 • n=325 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.
Baseline Clinical Outcomes Assessments (Safety Population) A-IADL-W	17.46 units on a scale STANDARD_DEVIATION 20.65 • n=161 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	16.00 units on a scale STANDARD_DEVIATION 18.42 • n=160 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	16.73 units on a scale STANDARD_DEVIATION 19.55 • n=321 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.
Baseline Clinical Outcomes Assessments (Safety Population) CDR-SB	2.97 units on a scale STANDARD_DEVIATION 1.45 • n=162 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	3.04 units on a scale STANDARD_DEVIATION 1.53 • n=163 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	3.00 units on a scale STANDARD_DEVIATION 1.49 • n=325 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.
Baseline Clinical Outcomes Assessments (Safety Population) DAD	93.0 units on a scale STANDARD_DEVIATION 10.34 • n=162 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	93.3 units on a scale STANDARD_DEVIATION 9.94 • n=161 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	93.2 units on a scale STANDARD_DEVIATION 10.13 • n=323 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.
Baseline Clinical Outcomes Assessments (Safety Population) MMSE	25.1 units on a scale STANDARD_DEVIATION 2.7 • n=162 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	25.5 units on a scale STANDARD_DEVIATION 2.7 • n=163 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.	25.3 units on a scale STANDARD_DEVIATION 2.7 • n=325 Participants • Not all patients had all baseline measures taken/assessed/collected at baseline.

PRIMARY outcome

Timeframe: Baseline to Week 78

Population: Full Analysis Set (FAS): The FAS includes all study subjects who received at least one dose of the study drug, had at least one baseline assessment and any post baseline efficacy assessment. All primary and secondary clinical efficacy analyses are conducted on this population.

Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-Cog13) scores. The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=162 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Primary Cognitive Efficacy Endpoint (ADAS-Cog13)	4.40 Score on a scale Standard Error 0.69	3.89 Score on a scale Standard Error 0.69

PRIMARY outcome

Timeframe: Entire study: approximately 82 weeks. (first dose of study drug until end of Safety Follow-up Visit at 28 +/- 7 days after the last dose (ie, 78-week treatment period plus 4-weeks follow-up after last dose up to total of 82 weeks)

Population: Safety Population: subjects who took at least 1 dose of any study drug are included.

Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAEs, and TEAEs leading to withdrawal.

Outcome measures

Outcome measures
Measure	Placebo n=162 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=163 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE) TEAE leading to discontinuation of study drug	4 Participants	13 Participants
Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE) TEAE	137 Participants	140 Participants
Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE) Study drug related TEAE	44 Participants	75 Participants
Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE) Serious TEAE	13 Participants	14 Participants
Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE) Serious study drug related TEAE	0 Participants	1 Participants
Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE) Study drug related TEAE leading to study drug discontinuation	1 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline to Week 78

Population: FAS

Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores calculated using the weighted average method (A-IADL-W score). The A-IADL Questionnaire is a 70-item informant-based computerized questionnaire aimed at detecting deficits in complex functions at the early stages of AD. Instrumental ADL can be described as the activities necessary to function independently in society. These activities include, but are not limited to, cooking, doing finances, and shopping. They are complex everyday tasks, determined by multiple cognitive processes and controlled processing. They can be distinguished from basic ADL, which include basic self-care skills. The A-IADL-W has a score range of 0-100 and is calculated as follows: (sum of all scores / number of questions scored) × 25. For A-IADL-W, higher scores indicates worse functioning or more impairment.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=162 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Key Secondary Endpoint (A-IADL-W)	13.59 score on a scale Standard Error 2.02	13.60 score on a scale Standard Error 2.00

SECONDARY outcome

Timeframe: Baseline to Week 78

Population: FAS

Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores. CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=162 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Key Secondary Endpoint (CDR-SB)	1.36 score on a scale Standard Error 0.21	1.05 score on a scale Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline to Week 78

Population: FAS

Change from baseline in Disability Assessment for Dementia (DAD)scores. The DAD consists of 40 items with a score range of 0-100 to evaluate the basic and instrumental activities of daily living of subjects with dementia. It is administered through an interview with the caregiver. Higher DAD scores indicate less disability or better function.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=162 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Functional Assessment (DAD)	-9.2 score on a scale Standard Error 1.7	-6.5 score on a scale Standard Error 1.7

SECONDARY outcome

Timeframe: Baseline to Week 78

Population: FAS

Change from baseline in Mini-Mental State Examination (MMSE) score. The MMSE is a measure of global cognition that is widely used for clinical staging of Alzheimer's Disease. It consists of 11 domains items for a score range of 0-30 to assess general cognitive function. Higher score on MMSE means better cognitive skills.

Outcome measures

Outcome measures
Measure	Placebo n=158 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=162 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Global Cognition Assessment (MMSE)	-2.03 score on a scale Standard Error 0.33	-1.60 score on a scale Standard Error 0.33

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: The Imaging Biomarker population included all subjects with an evaluable baseline vMRI assessment who had received at least 1 dose of study drug and had at least 1 evaluable post-baseline imaging vMRI assessment.

Change from baseline in total (bilateral) hippocampal volume (HV) (uL) as measured by Magnetic Resonance Imaging (MRI). HV atrophy is an early event in AD patients, especially in APOE4/4 homozygotes who show accelerated atrophy compared to APOE3/3 patients with Early AD. HV may be a marker of synaptic loss and neurodegeneration.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=146 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Imaging Biomarker Endpoint (Hippocampal Volume)	-418.5 microliters Standard Error 21.46	-345.0 microliters Standard Error 22.01

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population

Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=146 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Imaging Biomarker Endpoint (Cortical Thickness [Whole Cortex])	-0.060 mm Standard Error 0.003	-0.048 mm Standard Error 0.003

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population

Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. The Mayo Index refers specifically to the measurement of cortical thickness in the medial temporal lobe.

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=146 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Imaging Biomarker Endpoint (Cortical Thickness [Mayo Index])	-0.121 mm Standard Error 0.005	-0.099 mm Standard Error 0.005

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population

Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=146 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Imaging Biomarker Endpoint (Whole Brain Volume)	-17877.0 microliters Standard Error 955.98	-15056.0 microliters Standard Error 979.86

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population

Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=146 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Imaging Biomarker Endpoint (Ventricular Volume)	5186.3 microliters Standard Error 256.19	4028.9 microliters Standard Error 262.86

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: DTI-MRI Population defined as all participants who had an evaluable baseline DTI-MRI assessment, received at least one dose of study drug, and had at least one evaluable post-baseline DTI-MRI assessment.

Change from baseline in Grey Matter Mean Diffusivity (Bilateral Caudate) as measured by Diffusion Tensor Imaging - Magnetic Resonance Imaging (DTI-MRI). The mean diffusivity (MD) is the average of the three main diffusion values (eigenvalues) obtained from the diffusion tensor imaging (DTI). It is expressed as mm2/s. This unit quantifies the average rate of water diffusion across all directions within a tissue, providing an overall measure of tissue microstructural properties. Lower MD value suggests better maintenance of microstructural integrity of a given brain tissue. Positive treatment effects of ALZ-801 on DTI would present as lower mean diffusivity compared with the placebo group.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=105 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Imaging Biomarker Endpoint - DTI in Grey Matter Mean Diffusivity - Bilateral Caudate	0.000028 square millimeters per second (mm²/s) Standard Error 0.00000775	0.000007439 square millimeters per second (mm²/s) Standard Error 0.00000792

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: DTI-MRI Population

Change from baseline in Bilateral Fornix White Matter Mean Diffusivity as measured by Diffusion Tensor Imaging - Magnetic Resonance Imaging (DTI-MRI). The mean diffusivity (MD) is the average of the three main diffusion values (eigenvalues) obtained from the diffusion tensor imaging (DTI). It is expressed as mm2/s. This unit quantifies the average rate of water diffusion across all directions within a tissue, providing an overall measure of tissue microstructural properties. Lower MD value suggests better maintenance of microstructural integrity of a given brain tissue. Positive treatment effects of ALZ-801 on DTI would present as lower mean diffusivity compared with the placebo group.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=105 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Imaging Biomarker Endpoint - DTI in White Matter Mean Diffusivity (Bilateral Fornix)	0.0000237 square millimeters per second (mm²/s) Standard Error 0.0000058	0.000000843 square millimeters per second (mm²/s) Standard Error 0.00000593

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: DTI-MRI Population

Change from baseline in Bilateral Fornix White Matter Fractional Anisotropy as measured by Diffusion Tensor Imaging - Magnetic Resonance Imaging (DTI-MRI). Fractional anisotropy (FA) is a unitless, scalar value that measures the degree of anisotropic (directional) water diffusion within a voxel, ranging from 0 to 1. A value of 0 indicates perfectly isotropic (equal in all directions) diffusion, while a value of 1 indicates perfectly anisotropic (directional) diffusion. Higher FA value suggests better maintenance of microstructural integrity of a given brain tissue. Positive treatment effects of ALZ-801 on DTI would present as higher FA in the ALZ-801 group compared with the placebo group.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=105 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Imaging Biomarker Endpoint - White Matter Fractional Anisotropy (Bilateral Fornix)	-0.0154 Units on a scale (fractions 0-1) Standard Error 0.00332	-0.002089 Units on a scale (fractions 0-1) Standard Error 0.00336

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS MCI subgroup: all study subjects in the MCI subgroup who received at least one dose of the study drug, had at least one baseline assessment and any post baseline efficacy assessment.

Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-cog 13) scores at 78 weeks. The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=67 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cognitive Efficacy Endpoint (ADAS-Cog 13) - MCI Subgroup	4.10 Score on a scale Standard Error 0.81	1.97 Score on a scale Standard Error 0.83

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS Mild AD subgroup: all study subjects in the Mild AD subgroup who received at least one dose of the study drug, had at least one baseline assessment and any post baseline efficacy assessment.

Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-cog 13) scores at 78 weeks. The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=95 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cognitive Efficacy Endpoint (ADAS-Cog 13) - Mild Alzheimer's Disease(Mild AD) Subgroup	4.79 score on a scale Standard Error 0.75	5.66 score on a scale Standard Error 0.75

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS MCI Subgroup

Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores calculated using the weighted average method (A-IADL-W score). The A-IADL Questionnaire is a 70-item informant-based computerized questionnaire aimed at detecting deficits in complex functions at the early stages of AD. Instrumental ADL can be described as the activities necessary to function independently in society. These activities include, but are not limited to, cooking, doing finances, and shopping. They are complex everyday tasks, determined by multiple cognitive processes and controlled processing. They can be distinguished from basic ADL, which include basic self-care skills. The A-IADL-W has a score range of 0-100 and is calculated as follows: (sum of all scores / number of questions scored) × 25. For A-IADL-W, higher scores indicates worse functioning or more impairment.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=67 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
A-IADL-W - MCI Subgroup	4.84 score on a scale Standard Error 2.45	1.43 score on a scale Standard Error 2.50

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS Mild AD Subgroup

Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores calculated using the weighted average method (A-IADL-W score). The A-IADL Questionnaire is a 70-item informant-based computerized questionnaire aimed at detecting deficits in complex functions at the early stages of AD. Instrumental ADL can be described as the activities necessary to function independently in society. These activities include, but are not limited to, cooking, doing finances, and shopping. They are complex everyday tasks, determined by multiple cognitive processes and controlled processing. They can be distinguished from basic ADL, which include basic self-care skills. The A-IADL-W has a score range of 0-100 and is calculated as follows: (sum of all scores / number of questions scored) × 25. For A-IADL-W, higher scores indicates worse functioning or more impairment.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=95 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
A-IADL-W - Mild AD Subgroup	18.55 score on a scale Standard Error 2.21	22.20 score on a scale Standard Error 2.21

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS MCI Subgroup

Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores. CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=67 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
CDR-SB - MCI Subgroup	0.63 score on a scale Standard Error 0.26	-0.02 score on a scale Standard Error 0.27

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS Mild AD Subgroup

Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores. CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=95 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
CDR-SB - Mild AD Subgroup	1.84 score on a scale Standard Error 0.23	1.97 score on a scale Standard Error 0.24

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS MCI Subgroup

Change from baseline in Disability Assessment for Dementia (DAD)scores. The DAD consists of 40 items with a score range of 0-100 to evaluate the basic and instrumental activities of daily living of subjects with dementia. It is administered through an interview with the caregiver. Higher DAD scores indicate less disability or better function.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=67 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Functional Assessment (DAD) - MCI Subgroup	-6.3 score on a scale Standard Error 1.9	-0.2 score on a scale Standard Error 2.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS Mild AD Subgroup

Change from baseline in Disability Assessment for Dementia (DAD)scores. The DAD consists of 40 items with a score range of 0-100 to evaluate the basic and instrumental activities of daily living of subjects with dementia. It is administered through an interview with the caregiver. Higher DAD scores indicate less disability or better function.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=95 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Functional Assessment (DAD) - Mild AD Subgroup	-11.1 score on a scale Standard Error 1.8	-11.6 score on a scale Standard Error 1.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS MCI Subgroup

Change from baseline in Mini-Mental State Examination (MMSE) score. The MMSE is a measure of global cognition that is widely used for clinical staging of Alzheimer's Disease. It consists of 11 domains items for a score range of 0-30 to assess general cognitive function. Higher score on MMSE means better cognitive skills.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=67 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Global Cognition Assessment (MMSE) - MCI Subgroup	-1.4 Score on a scale Standard Error 0.4	-0.5 Score on a scale Standard Error 0.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: FAS Mild AD Subgroup

Change from baseline in Mini-Mental State Examination (MMSE) score. The MMSE is a measure of global cognition that is widely used for clinical staging of Alzheimer's Disease. It consists of 11 domains items for a score range of 0-30 to assess general cognitive function. Higher score on MMSE means better cognitive skills.

Outcome measures

Outcome measures
Measure	Placebo n=100 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=95 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Global Cognition Assessment (MMSE) - Mild AD Subgroup	-2.6 score on a scale Standard Error 0.4	-2.7 score on a scale Standard Error 0.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population MCI Subgroup: this population included all subjects in the MCI subgroup with an evaluable baseline vMRI assessment who had received at least 1 dose of study drug and had at least 1 evaluable post-baseline imaging vMRI assessment.

Change from baseline in total (bilateral) hippocampal volume (HV) (uL) as measured by Magnetic Resonance Imaging (MRI). HV atrophy is an early event in AD patients, especially in APOE4/4 homozygotes who show accelerated atrophy compared to APOE3/3 patients with Early AD. HV may be a marker of synaptic loss and neurodegeneration.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=61 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Hippocampal Volume (MCI Subgroup)	-411.2 microliters Standard Error 29.60	-303.1 microliters Standard Error 30.16

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population Mild AD Subgroup: this population included all subjects with an evaluable baseline vMRI assessment who had received at least 1 dose of study drug and had at least 1 evaluable post-baseline imaging vMRI assessment.

Change from baseline in total (bilateral) hippocampal volume (HV) (uL) as measured by Magnetic Resonance Imaging (MRI). HV atrophy is an early event in AD patients, especially in APOE4/4 homozygotes who show accelerated atrophy compared to APOE3/3 patients with Early AD. HV may be a marker of synaptic loss and neurodegeneration.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=85 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Hippocampal Volume (Mild AD Subgroup)	-423.2 microliters Standard Error 23.27	-371.8 microliters Standard Error 24.75

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population MCI Subgroup

Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=61 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cortical Thickness (Whole Cortex) (MCI Subgroup)	-0.059 mm Standard Error 0.004	-0.038 mm Standard Error 0.004

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population Mild AD Subgroup

Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=85 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cortical Thickness (Whole Cortex) (Mild AD Subgroup)	-0.061 mm Standard Error 0.003	-0.054 mm Standard Error 0.003

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population MCI Subgroup

Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. The Mayo Index refers specifically to the measurement of cortical thickness in the medial temporal lobe versus the whole cortex.

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=61 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cortical Thickness (Mayo Index) (MCI Subgroup)	-0.117 mm Standard Error 0.007	-0.084 mm Standard Error 0.007

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population Mild AD Subgroup

Change from baseline in total (bilateral) cortical thickness (mm) as measured by MRI. Brain MRI studies in Alzheimer's Disease patients show progressive cortical atrophy, reflecting progressive neurodegeneration. The Mayo Index refers specifically to the measurement of cortical thickness in the medial temporal lobe versus the whole cortex.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=85 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cortical Thickness (Mayo Index) (Mild AD Subgroup)	-0.123 mm Standard Error 0.006	-0.109 mm Standard Error 0.006

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population MCI Subgroup

Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=61 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Whole Brain Volume (MCI Subgroup)	-17559.5 microliters Standard Error 1417.91	-13715.7 microliters Standard Error 1449.14

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population Mild AD Subgroup

Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=85 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Whole Brain Volume (Mild AD Subgroup)	-18081.4 microliters Standard Error 1056.74	-15917.1 microliters Standard Error 1143.24

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population MCI Subgroup

Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=61 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Ventricular Volume (MCI Subgroup)	4490.5 microliters Standard Error 343.65	3178.2 microliters Standard Error 350.44

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population Mild AD Subgroup

Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=85 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Ventricular Volume (Mild AD Subgroup)	5630.4 microliters Standard Error 274.91	4573.4 microliters Standard Error 294.71

POST_HOC outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population

Change from baseline in total (bilateral) cerebellar volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=144 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=146 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cerebellar Volume	-577.0 microliters Standard Error 62.50	-427.2 microliters Standard Error 64.70

POST_HOC outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population MCI Subgroup

Change from baseline in total (bilateral) cerebellar volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=52 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=61 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cerebellar Volume (MCI Subgroup)	-566.8 microliters Standard Error 91.78	-428.8 microliters Standard Error 94.09

POST_HOC outcome

Timeframe: Baseline to Week 78

Population: Imaging Biomarker Population Mild AD Subgroup

Change from baseline in total (bilateral) cerebellar volume (uL) as measured by Magnetic Resonance Imaging (MRI).

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=85 Participants ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Cerebellar Volume (Mild AD Subgroup)	-583.6 microliters Standard Error 68.62	-426.2 microliters Standard Error 75.18

Adverse Events

Placebo

Serious events: 13 serious events

Other events: 94 other events

Deaths: 0 deaths

ALZ-801

Serious events: 15 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Aidan Power

Alzheon

Phone: (508) 861-7709

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Placebo n=162 participants at risk Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Placebo Comparator: Placebo: Placebo tablet BID	ALZ-801 n=163 participants at risk ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one table of ALZ-801 265mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265mg tablet BID. Experimental: ALZ-801: ALZ-801 tablet 265 mg BID
Injury, poisoning and procedural complications Fall	6.8% 11/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	6.1% 10/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Nervous system disorders Headache	8.0% 13/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	5.5% 9/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Infections and infestations Urinary Tract Infection	8.0% 13/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	6.1% 10/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Nervous system disorders Cerebral Microhaemorrhage	7.4% 12/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	4.9% 8/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Metabolism and nutrition disorders Decreased Appetite	1.9% 3/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	9.8% 16/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Nervous system disorders Dizziness	5.6% 9/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	5.5% 9/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Gastrointestinal disorders Vomiting	1.2% 2/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	9.8% 16/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Infections and infestations COVID-19	20.4% 33/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	21.5% 35/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Gastrointestinal disorders Nausea	4.9% 8/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	25.8% 42/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Investigations Weight Decreased	7.4% 12/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	14.1% 23/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Nervous system disorders Amyloid related imaging abnormality - microhaemorrhages and heamosiderin deposits	5.6% 9/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	3.7% 6/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Psychiatric disorders Anxiety	5.6% 9/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	3.7% 6/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Musculoskeletal and connective tissue disorders Back pain	6.8% 11/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	3.1% 5/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Vascular disorders Hypertension	5.6% 9/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	4.3% 7/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.
Gastrointestinal disorders Diarrhoea	5.6% 9/162 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.	4.9% 8/163 • All AEs (deaths, Serious Adverse Events, Other Adverse Events) were recorded for up to 95 weeks (13 weeks screening + 78-week treatment + 4 weeks follow-up). All AEs were collected from ICF signing at screening through Safety Follow-up Visit 4 weeks after last efficacy visit at week 78. Medical conditions present at screening were captured as medical history. However, if a condition deteriorated, it was recorded as an AE.