An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early AD Subjects (APOLLOE4)

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Efficacy, Safety and Biomarker Effects of ALZ-801 in Subjects With Early Alzheimer's Disease and APOE4/4 Genotype

This study is being conducted to evaluate the safety and efficacy of ALZ-801 in Early Alzheimer's disease (AD) subjects with the APOE4/4 genotype. This is a double-blind, randomized trial with one dose of ALZ-801 compared to placebo.

Study Overview

• Status: Completed
• Conditions: Early Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo Comparator: Placebo; Drug: Experimental: ALZ-801

Detailed Description

This is a multi-center, double-blind study that will evaluate 265 mg twice daily (BID) of ALZ-801, an oral tablet, over 78 weeks as a treatment for subjects (50-80 years old) with Early AD who are homozygous for the ε4 allele of the apolipoprotein gene (APOE4 homozygous or APOE4/4). The primary efficacy outcome assessment is a measure of cognition (ADAS-cog 13). Additional measures of global and functional impairments will also be assessed. Imaging and soluble biomarkers of AD and neurodegeneration will be measured and a sub-study to evaluate cerebrospinal fluid (CSF) biomarkers is also included.

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • OCT Research ULC (dba Okanagan Clinical Trials)
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1N2
      • Centricity Research
    • New Minas, Nova Scotia, Canada, B4N 3R7
      • Centricity Research
  • Ontario
    • Ottawa, Ontario, Canada, K1Z 1G3
      • Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Centre - Redefining Healthy Aging
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Recherches Neuro-Hippocampe Inc. d/b/a Clinique de la Mémoire de l'Outaouais
• Czechia
  • Brno, Czechia, 656 91
    • Fakultní nemocnice u sv. Anny v Brně (St. Anne's University Hospital)
  • Brno, Czechia, 602 00
    • Medica 111, Spol. s r.o. - Neurologicka a Rehabilitacni Ambulance Brno, Centralni Pracoviste v Brne
  • Prague, Czechia, 160 00
    • Neuropsychiatrie s.r.o.
  • Rychnov nad Kněžnou, Czechia, 51601
    • Vestra Clinics - Dedicated Research Clinics
• France
  • Marseille, France, 13385
    • Centre Hospitalier Universitaire de Marseille - Hôpital de la Timone
  • Montpellier, France, 43431
    • Hopital Gui de Chauliac - CHRU de Montpellier
  • Paris, France, 75475
    • Hopital Lariboisiere - Fernand-Widal - AP-HP
  • Rouen, France, 76031
    • Centre Hospitalier Universitaire (CHU) Hopitaux de Rouen
  • Strasbourg, France, 67200
    • Hopitaux Universitaires de Strasbourg Centre d'Investigation Clinique
  • Toulouse, France, 31059
    • Centre de Recherche Clinique du Gerontopole - CHU Toulouse
  • Villeurbanne, France, 69100
    • Centre de Recherche-Hopital Geriatrique de Charpennes
• Germany
  • Aachen, Germany, 52074
    • University Hospital RWTH Aachen Neurological Study Center
  • München, Germany, 80336
    • Klinikum der Universitaet Muenchen Innenstadt
  • Tübingen, Germany, 72076
    • Universitätsklinik fuer Psychiatrie und Psychotherapie
  • Westerstede, Germany, 26655
    • Studienzentrum Nord-West
• Iceland
  • Reykjavik, Iceland, 101
    • Memory Clinic, Landspitali University Hospital
• Netherlands
  • 's-Hertogenbosch, Netherlands, 5223 LA
    • Brain Research Center Den Bosch
  • Amsterdam, Netherlands, 1081 GN
    • Brain Research Center Amsterdam
  • Zwolle, Netherlands, 8025 AZ
    • Brain Research Center Zwolle
• Spain
  • Barcelona, Spain, 08028
    • Fundacia ACE - Institut Catala de Neurociencies Aplicadas
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Terrassa, Spain, 08221
    • Hospital Universitari MútuaTerrassa
  • Valencia, Spain, 46017
    • Centro Hospital Universitario Dr. Preset
• United Kingdom
  • Bristol, United Kingdom, BS32 4SY
    • Re:Cognition Health Ltd Bristol
  • London, United Kingdom, EC2Y 8EA
    • St. Pancras Clinical Research
  • Winchester, United Kingdom, SO21 1HU
    • Re-Cognition Health Ltd Winchester
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8BT
      • Re-Cognition Health Ltd Plymouth
  • Greater London
    • London, Greater London, United Kingdom, W1G 9JF
      • Re-Cognition Health Ltd London
  • North Lanarkshire
    • Motherwell, North Lanarkshire, United Kingdom, ML1 4UF
      • NeuroClin Glasgow Ltd
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7YD
      • Re-Cognition Health Ltd Guildford
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B16 8LT
      • Re-Cognition Health Ltd Birmingham
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience
    • Scottsdale, Arizona, United States, 85297
      • CCT Research
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research
    • Irvine, California, United States, 92780
      • Tilda Research
    • La Jolla, California, United States, 92037
      • UCSD Shiley-Marcos Alzheimer's Disease Research Center
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Institute
    • Long Beach, California, United States, 90806
      • Collaborative NeuroScience Network LLC
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Pasadena, California, United States, 91105
      • SC3 Research Group
    • Sacramento, California, United States, 95816
      • Sutter Health
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute, Headlands Site
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Hialeah, Florida, United States, 33016
      • Galiz Research
    • Jupiter, Florida, United States, 33458
      • Alphab Global Research
    • Lady Lake, Florida, United States, 32159
      • Charter Research
    • Maitland, Florida, United States, 32751
      • K2 Medical Research, Llc
    • Miami, Florida, United States, 33137
      • Miami Jewish Health
    • Miami, Florida, United States, 33144
      • Y & L Advance Health Care, Inc /DBA Elite Clinical Research
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Naples, Florida, United States, 34105
      • Aqualane Clinical Research
    • Orlando, Florida, United States, 32819
      • Headlands Research Orlando
    • Orlando, Florida, United States, 32803
      • Charter Research
    • Palm Beach Gardens, Florida, United States, 33410
      • Advanced Research Consultants
    • Pompano Beach, Florida, United States, 33064
      • Quantum CNS Clinical Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Stuart, Florida, United States, 34997
      • ALZ Research and Treatment Center (A.R.T.C.)
    • Wellington, Florida, United States, 33414
      • ALZ Research and Treatment Center (A.R.T.C.)
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columbus Memory Center
    • Decatur, Georgia, United States, 30030
      • Sandhill Research, LLC
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Center (LSUHSC)
  • Massachusetts
    • Plymouth, Massachusetts, United States, 02360
      • Headlands Research Eastern MA
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • WR-CRCN
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Center
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany
    • New York, New York, United States, 10016
      • NYU Alzheimer's Disease Research Center
    • Orangeburg, New York, United States, 10962
      • Kline Institute for Psychiatric Research
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Greensboro, North Carolina, United States, 27410
      • Triad Clinical Trials
    • Matthews, North Carolina, United States, 28105
      • AMC Research
  • Ohio
    • Canton, Ohio, United States, 44718
      • NeuroScience Research Center
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research
  • Oregon
    • Portland, Oregon, United States, 97225
      • Center for Cognitive Health
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt Center for Cognitive Medicine
  • Texas
    • Houston, Texas, United States, 77054
      • UT Health Science Center at Houston
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Re:Cognition Health
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical diagnosis of MCI or Mild Dementia due to AD consistent with the National Institute on Aging-Alzheimer's Association (NIA-AA) Working Group Criteria.
• Homozygous for the ε4 allele of the apolipoprotein E gene (APOE4/4).
• MMSE score at Screening of 22 to 30 (inclusive).
• CDR - Global score of 0.5 or 1 and CDR Memory Box Score of ≥ 0.5.
• RBANS delayed memory index score ≤ 85.
• Evidence of progressive memory loss over the last 12 months per investigator assessment

Exclusion Criteria:

• Brain magnetic resonance imaging (MRI) indicative of significant abnormality per central reader, other than AD related atrophy. Computed tomography (CT) scan acceptable for subjects who cannot undergo MRI.
• Diagnosis of neurodegenerative disorder other than AD.
• Diagnosis of major depressive disorder (MDD) within one year prior to screening.
• Currently taking memantine or has taken memantine within 12 weeks prior to the Baseline Visit.
• History of suicidal behavior within one year prior to screening or has ongoing suicidal ideation.
• History of seizures, excluding febrile seizures of childhood or a single distant seizure (> 5 years).
• Medically confirmed history of recent cerebral infarct or transient ischemic attack within one year prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study	Drug: Placebo Comparator: Placebo; Placebo tablet BID
Experimental: ALZ-801; ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one tablet of ALZ-801 265 mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265 mg tablet twice daily (BID).	Drug: Placebo Comparator: Placebo; Placebo tablet BID; Drug: Experimental: ALZ-801; ALZ-801 tablet 265 mg once daily in the evening for the first 2 weeks, then ALZ-801 tablet 265 mg BID; Other Names: valiltramiprosate; tramiprosate prodrug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Cognitive Efficacy Endpoint (ADAS-Cog13)	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.	Baseline to Week 78
Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE)	Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAEs, and TEAEs leading to withdrawal.	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key Secondary Endpoint (A-IADL-W)	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.	Baseline to Week 78
Key Secondary Endpoint (CDR-SB)	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.	Baseline to Week 78
Functional Assessment (DAD)	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.	Baseline to Week 78
Global Cognition Assessment (MMSE)	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.	Baseline to Week 78

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Imaging Biomarker Endpoint (Hippocampal Volume)	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.	Baseline to Week 78
Imaging Biomarker Endpoint (Cortical Thickness [Whole Cortex])	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.	Baseline to Week 78
Imaging Biomarker Endpoint (Cortical Thickness [Mayo Index])	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.	Baseline to Week 78
Imaging Biomarker Endpoint (Whole Brain Volume)	Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI).	Baseline to Week 78
Imaging Biomarker Endpoint (Ventricular Volume)	Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI).	Baseline to Week 78
Imaging Biomarker Endpoint - DTI in Grey Matter Mean Diffusivity - Bilateral Caudate	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.	Baseline to Week 78
Imaging Biomarker Endpoint - DTI in White Matter Mean Diffusivity (Bilateral Fornix)	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.	Baseline to Week 78
Imaging Biomarker Endpoint - White Matter Fractional Anisotropy (Bilateral Fornix)	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.	Baseline to Week 78
Cognitive Efficacy Endpoint (ADAS-Cog 13) - MCI Subgroup	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.	Baseline to Week 78
Cognitive Efficacy Endpoint (ADAS-Cog 13) - Mild Alzheimer's Disease(Mild AD) Subgroup	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.	Baseline to Week 78
A-IADL-W - 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.	Baseline to Week 78
A-IADL-W - 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.	Baseline to Week 78
CDR-SB - 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.	Baseline to Week 78
CDR-SB - 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.	Baseline to Week 78
Functional Assessment (DAD) - 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.	Baseline to Week 78
Functional Assessment (DAD) - 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.	Baseline to Week 78
Global Cognition Assessment (MMSE) - 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.	Baseline to Week 78
Global Cognition Assessment (MMSE) - 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.	Baseline to Week 78
Hippocampal Volume (MCI Subgroup)	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.	Baseline to Week 78
Hippocampal Volume (Mild AD Subgroup)	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.	Baseline to Week 78
Cortical Thickness (Whole Cortex) (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.	Baseline to Week 78
Cortical Thickness (Whole Cortex) (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.	Baseline to Week 78
Cortical Thickness (Mayo Index) (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.	Baseline to Week 78
Cortical Thickness (Mayo Index) (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.	Baseline to Week 78
Whole Brain Volume (MCI Subgroup)	Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI).	Baseline to Week 78
Whole Brain Volume (Mild AD Subgroup)	Change from baseline in whole brain volume (uL) as measured by Magnetic Resonance Imaging (MRI).	Baseline to Week 78
Ventricular Volume (MCI Subgroup)	Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI).	Baseline to Week 78
Ventricular Volume (Mild AD Subgroup)	Change from baseline in total (bilateral) ventricular volume (uL) as measured by Magnetic Resonance Imaging (MRI).	Baseline to Week 78

Collaborators and Investigators

• Sponsor: Alzheon Inc.
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Susan Abushakra, MD, Alzheon Inc.

Publications and helpful links

General Publications

• Abushakra S, Power A, Watson D, Porsteinsson A, Sabbagh M, MacSweeney E, Cohen S, Boada Rovira M, Doraiswamy PM, Liang E, Flint S, Kesslak JP, McLaine R, Albayrak A, Schaefer J, Yu J, Tolar L, Dickson S, Hey JA, Tolar M. Clinical Efficacy, Safety and Imaging Effects of Oral Valiltramiprosate in APOEepsilon4/epsilon4 Homozygotes with Early Alzheimer's Disease: Results of the Phase III, Randomized, Double-Blind, Placebo-Controlled, 78-Week APOLLOE4 Trial. Drugs. 2025 Sep 28. doi: 10.1007/s40265-025-02250-5. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2021
• Primary Completion (Actual): May 29, 2024
• Study Completion (Actual): July 29, 2024

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Estimated): November 7, 2025
• Last Update Submitted That Met QC Criteria: October 23, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; GABA Agents; Anticonvulsants; GABA Agonists; Tramiprosate
• Other Study ID Numbers: ALZ-801-AD301; R01AG065253 (U.S. NIH Grant/Contract); 2020-005755-20 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No