Long-term Extension of Phase 3 Study of ALZ- 801 in APOE4/4 Early AD Subjects (APOLLOE4-LTE)

Long-term Extension of 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 long-term safety and efficacy of ALZ-801 in Early Alzheimer's disease (AD) subjects with the APOE4/4 genotype. This is an open-label trial of treatment with ALZ-801.

Study Overview

• Status: Active, not recruiting
• Conditions: Early Alzheimer's Disease
• Intervention / Treatment: Drug: Experimental: ALZ-801

Detailed Description

This is a long-term extension study of the Phase 3, multicenter, randomized, double-blind, placebo-controlled study of the efficacy, safety, and imaging biomarker effects of ALZ-801 in subjects with Early Alzheimer's Disease and APOE4/4 genotype. Subjects who at initial screening for the Phase 3 study were 50-80 years old, had a clinical diagnosis of AD, carried the APOE4/4 genotype, and were at the early stage of disease (Early AD], who complete at least 78 weeks of the Phase 3 study while on study medication, were eligible for enrollment. Subjects will be treated for 104 weeks with ALZ-801, followed by a 4-week safety follow-up visit after the last dose of ALZ-801. Clinical trial sites, subjects and their study partner will remain blinded to the treatment (ALZ-801 or placebo) that they received in the core Phase 3 study. 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 biomarkers of AD and neurodegeneration will be measured.

• Study Type: Interventional
• Enrollment (Actual): 163
• 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
  • 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
• United Kingdom
  • Bristol, United Kingdom, BS32 4SY
    • Re-Cognition Health Ltd Bristol
  • 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, Inc.
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Institute
    • Sacramento, California, United States, 95816
      • Sutter Health
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute, Headlands Site
    • Maitland, Florida, United States, 32751
      • K2 Medical Research, LLC
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Naples, Florida, United States, 34105
      • Aqualane Clinical Research
    • Orlando, Florida, United States, 32803
      • Charter 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
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center
  • Massachusetts
    • Plymouth, Massachusetts, United States, 02360
      • Headlands Research Eastern MA
  • 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
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27410
      • Triad Clinical Trials
    • Matthews, North Carolina, United States, 28105
      • AMC Research
  • Oregon
    • Portland, Oregon, United States, 97225
      • Center for Cognitive Health
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
  • 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject has completed the Week 78 of the Phase 3 core study (ALZ-801-AD301) while on study drug.
• Subject has a reliable study partner who has sufficient contact with the subject to be able to provide accurate information about the subject's cognitive and functional abilities.

Exclusion Criteria:

• Significant worsening of medical conditions that may preclude completion of this study.
• Evidence of symptomatic or new moderate-severe radiologic ARIA at baseline.
• Has received (or plans to receive) amyloid antibodies since completing Phase 3 core study (ALZ-801-AD301).
• Subject taking any prohibited medications per protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: ALZ-801; ALZ-801 265 mg BID tablet orally. Subjects will take one 265 mg tablet of ALZ-801 in the evening during the first 4 weeks of the study; thereafter, they will take one 265 mg tablet BID.	Drug: Experimental: ALZ-801; ALZ-801 265 mg BID tablet orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary cognitive efficacy endpoint 1	Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-Cog 13), from baseline of Phase 3 core study (ALZ-801-AD301) to Week 52 and Week 104 of this long-term extension study (ALZ-801-AD351).	Week 104
Primary cognitive efficacy endpoint 2	Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-Cog 13), from baseline of this study to Week 52 and Week 104.	Week 104
Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAEs)	Safety and tolerability as measured by incidence, nature and severity of treatment emergent adverse events (TEAE), serious TEAE, and TEAE leading to withdrawal.	Week 104
Primary imaging biomarker endpoint 1	Change from baseline in total hippocampal volume (mm3) as measured by Magnetic Resonance Imaging (MRI), from baseline of the Phase 3 core study (ALZ-801-AD301) to Week 52 and Week 104 of this long-term extension study (ALZ-801-AD351).	Week 104
Primary imaging biomarker endpoint 2	Change from baseline in total hippocampal volume (mm3) as measured by Magnetic Resonance Imaging (MRI), from baseline of this study to Week 52 and Week 104.	Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary functional efficacy endpoint	Change from baseline of the Phase 3 core study, and from baseline and from Week 52 of this study, in Disability Assessment for Dementia scores.	Week 104
Secondary functional efficacy endpoint	Change from baseline of the Phase 3 core study, and from baseline and from Week 52 of this study, in Amsterdam - Instrumental Activities of Daily Living scores.	Week 104
Secondary global assessment efficacy endpoint	Change from baseline of the Phase 3 core study, and from baseline and from Week 52 of this study, in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores.	Week 104
Secondary cognitive efficacy endpoint 1	Change from baseline of the Phase 3 core study, and from baseline and from Week 52 of this study, in Alzheimer's Disease Assessment Scale - Cognitive Subscale 11.	Week 104
Secondary cognitive efficacy endpoint 2	Change from baseline of the Phase 3 core study, and from baseline and from Week 52 of this study, in Neuropsychiatric Inventory.	Week 104
Secondary cognitive efficacy endpoint 3	Change from baseline of the Phase 3 core study, and from baseline and from Week 52 of this study, in Mini-Mental State Examination.	Week 104
Secondary imaging biomarker endpoint	Change from baseline of the Phase 3 core study (ALZ-801-AD301) and from baseline of this long-term extension study (ALZ-801-AD351) in cortical thickness, whole brain volume and ventricular volume (mm3) as measured by Magnetic Resonance Imaging (MRI) to Weeks 26, 52, 78 and 104.	Week 104
Secondary fluid biomarker endpoint	Change from baseline of the Phase 3 core study, and from baseline and from Week 52 of this study in plasma p-tau181, Aβ 42, Aβ 40, GFAP, and NfL levels.	Week 104

Collaborators and Investigators

• Sponsor: Alzheon Inc.
• Investigators: Principal Investigator: Susan Abushakra, MD, Alzheon Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: March 5, 2024
• First Submitted That Met QC Criteria: March 5, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Nervous System Diseases; Dementia; Alzheimer Disease; Central Nervous System Diseases; Neurodegenerative Diseases; Mental Disorders; Neurocognitive Disorders; Tauopathies
• Additional Relevant MeSH Terms: Brain Diseases; Alzheimer Disease; Mental Disorders; Dementia; Nervous System Diseases; Neurodegenerative Diseases; Central Nervous System Diseases; Neurocognitive Disorders; Tauopathies
• Other Study ID Numbers: ALZ-801-AD351

Drug and device information, study documents

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