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Completed

NCT Number: NCT04770220

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

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.

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Key information

Conditions

Early Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

50 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

OCT Research ULC (dba Okanagan Clinical Trials), Kelowna, British Columbia, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Experimental: ALZ-801

Drug

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

Placebo Comparator: Placebo

Drug

Placebo tablet BID

Primary outcomes

  1. Primary Cognitive Efficacy Endpoint (ADAS-Cog13)

    Time frame: Baseline to Week 78

    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.

  2. Incidence, Nature, and Severity of Treatment Emergent Adverse Events (TEAE)

    Time frame: 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)

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

Secondary outcomes

  1. Key Secondary Endpoint (A-IADL-W)

    Time frame: Baseline to Week 78

    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.

  2. Key Secondary Endpoint (CDR-SB)

    Time frame: Baseline to Week 78

    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.

  3. Functional Assessment (DAD)

    Time frame: Baseline to Week 78

    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.

  4. Global Cognition Assessment (MMSE)

    Time frame: Baseline to Week 78

    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.

Other outcomes

  1. Imaging Biomarker Endpoint (Hippocampal Volume)

    Time frame: Baseline to Week 78

    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.

  2. Imaging Biomarker Endpoint (Cortical Thickness [Whole Cortex])

    Time frame: Baseline to Week 78

    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.

  3. Imaging Biomarker Endpoint (Cortical Thickness [Mayo Index])

    Time frame: Baseline to Week 78

    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.

  4. Imaging Biomarker Endpoint (Whole Brain Volume)

    Time frame: Baseline to Week 78

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

  5. Imaging Biomarker Endpoint (Ventricular Volume)

    Time frame: Baseline to Week 78

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

  6. Imaging Biomarker Endpoint - DTI in Grey Matter Mean Diffusivity - Bilateral Caudate

    Time frame: Baseline to Week 78

    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.

  7. Imaging Biomarker Endpoint - DTI in White Matter Mean Diffusivity (Bilateral Fornix)

    Time frame: Baseline to Week 78

    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.

  8. Imaging Biomarker Endpoint - White Matter Fractional Anisotropy (Bilateral Fornix)

    Time frame: Baseline to Week 78

    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.

  9. Cognitive Efficacy Endpoint (ADAS-Cog 13) - MCI Subgroup

    Time frame: Baseline to Week 78

    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.

  10. Cognitive Efficacy Endpoint (ADAS-Cog 13) - Mild Alzheimer's Disease(Mild AD) Subgroup

    Time frame: Baseline to Week 78

    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.

  11. A-IADL-W - MCI Subgroup

    Time frame: Baseline to Week 78

    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.

  12. A-IADL-W - Mild AD Subgroup

    Time frame: Baseline to Week 78

    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.

  13. CDR-SB - MCI Subgroup

    Time frame: Baseline to Week 78

    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.

  14. CDR-SB - Mild AD Subgroup

    Time frame: Baseline to Week 78

    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.

  15. Functional Assessment (DAD) - MCI Subgroup

    Time frame: Baseline to Week 78

    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.

  16. Functional Assessment (DAD) - Mild AD Subgroup

    Time frame: Baseline to Week 78

    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.

  17. Global Cognition Assessment (MMSE) - MCI Subgroup

    Time frame: Baseline to Week 78

    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.

  18. Global Cognition Assessment (MMSE) - Mild AD Subgroup

    Time frame: Baseline to Week 78

    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.

  19. Hippocampal Volume (MCI Subgroup)

    Time frame: Baseline to Week 78

    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.

  20. Hippocampal Volume (Mild AD Subgroup)

    Time frame: Baseline to Week 78

    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.

  21. Cortical Thickness (Whole Cortex) (MCI Subgroup)

    Time frame: Baseline to Week 78

    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.

  22. Cortical Thickness (Whole Cortex) (Mild AD Subgroup)

    Time frame: Baseline to Week 78

    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.

  23. Cortical Thickness (Mayo Index) (MCI Subgroup)

    Time frame: Baseline to Week 78

    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.

  24. Cortical Thickness (Mayo Index) (Mild AD Subgroup)

    Time frame: Baseline to Week 78

    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.

  25. Whole Brain Volume (MCI Subgroup)

    Time frame: Baseline to Week 78

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

  26. Whole Brain Volume (Mild AD Subgroup)

    Time frame: Baseline to Week 78

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

  27. Ventricular Volume (MCI Subgroup)

    Time frame: Baseline to Week 78

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

  28. Ventricular Volume (Mild AD Subgroup)

    Time frame: Baseline to Week 78

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

Sponsors and collaborators

Lead sponsor

Alzheon Inc.

Industry

Collaborators

  • National Institute on Aging (NIA)

Registry information

Official study title

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

Acronym: APOLLOE4

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Feb 25, 2021
Registry last updated
Nov 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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