Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease

NCT04693520 | Completed Phase 2 FDA Drug

• 1 other identifier: ALZ-801-201ADBM
• Study Type: interventional
• Target: 84
• Locations: 2 countries
• Sites: 6

Brief Summary

The study will investigate the effects of oral ALZ-801, in subjects with Early AD who have the APOE4/4 or APOE3/4 genotype, on the biomarkers of core AD pathology. The objectives of this study include determining the efficacy and safety/tolerability of ALZ-801. In addition, the study will evaluate the extended PK profile over 8 hours in 16 subjects after 65 weeks of treatment.

Conditions

Early Alzheimer's Disease

Outcome Measures

Primary Outcomes (3)

• Plasma Biomarker of Core AD Pathology

  Percent change from baseline in p-tau181

  Week 104

• 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 TEAE, and TEAE leading to withdrawal.

  Week 108

• Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume

  Change from baseline in hippocampal volume measured in mm3

  Weeks 104

Secondary Outcomes (5)

• Plasma Biomarkers of AD and Neurodegeneration

  Weeks 104

• vMRI Biomarker - Ventricular volume and Cortical Thickness

  Weeks 104, 156 and 208

• Additional CSF Biomarkers of AD Pathology and Neurodegeneration

  Weeks 104

• Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE)

  Week 160 and week 212

• Volumetric Magnetic Resonance Imaging (vMRI) Biomarker - Hippocampal Volume

  Week 156 and week 208

Other Outcomes (5)

• Cognitive assessment - Rey Auditory Verbal Learning Test (RAVLT)

  Weeks 104, week 156 and week 208

• Cognitive Assessment - Digit Symbol Substitution Test (DSST)

  Weeks 104, Week 156 and Week 208

• Functional Assessment - Amsterdam Instrumental Activities of Daily Living (A-IADL)

  Weeks 104, Week 156 and Week 208

Study Arms (1)

Active treatment

EXPERIMENTAL

ALZ-801 265 mg tablets once daily for two weeks and twice daily thereafter

Drug: ALZ-801

Interventions

ALZ-801 DRUG

ALZ-801 265 mg twice daily (BID)

Active treatment

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 50 and 80 years, inclusive.
• Early Alzheimer's Disease (AD): a diagnosis of Probable AD Dementia or Mild Cognitive Impairment (MCI) due to AD in accordance with the National Institute on Aging-Alzheimer's Association (NIA-AA) Working Group Criteria \[Albert et al, 2011; McKhann et al, 2011\].
• One of the following apolipoprotein E (APOE) genotypes - either APOE4/4 (homozygous) or APOE3/4 (heterozygous).
• MMSE score 22 to 30 inclusive; Clinical Dementia Rating (CDR)-Global Score of 0.5 or 1.0, and CDR Memory Box Score of ≥ 0.5.
• Documented confirmation of AD diagnosis by either positive amyloid positron emission tomography (PET) or positive CSF AD signature. Subjects without documented positive AD biomarker status must have a positive CSF biomarker result from a sample provided at screening.
• Stable doses of acetylcholinesterase for the duration of the study are allowed.

You may not qualify if:

• Brain MRI at screening indicative of significant abnormality
• Diagnosis of neurodegenerative disorder other than AD
• Current diagnosis of Major Depressive Disorder (MDD)
• Concomitant treatment with memantine.

Sponsors & Collaborators

• Alzheon Inc.: lead

Study Sites (6)

St. Anne's University Hospital

Brno, Czechia

Location

Motol University Hospital

Prague, Czechia

Location

Vestra Clinics

Rychnov nad Kněžnou, Czechia

Location

Brain Research Center

's-Hertogenbosch, Netherlands

Location

Brain Research Center

Amsterdam, Netherlands

Location

Brain Research Center

Zwolle, Netherlands

Location

Related Publications (3)

• Hey JA, Yu JY, Abushakra S, Schaefer JF, Power A, Kesslak P, Paul J, Tolar M. Clinical Pharmacokinetics of Oral ALZ-801/Valiltramiprosate in a 2-Year Phase 2 Trial of APOE4 Carriers with Early Alzheimer's Disease. Clin Pharmacokinet. 2025 Mar;64(3):407-424. doi: 10.1007/s40262-025-01482-8. Epub 2025 Feb 5.

  PMID: 39907966 DERIVED

• Hey JA, Yu JY, Abushakra S, Schaefer JF, Power A, Kesslak P, Tolar M. Analysis of Cerebrospinal Fluid, Plasma beta-Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease Using Quantitative Systems Pharmacology Model. Drugs. 2024 Jul;84(7):825-839. doi: 10.1007/s40265-024-02068-7. Epub 2024 Jun 20.

  PMID: 38902572 DERIVED

• Hey JA, Abushakra S, Blennow K, Reiman EM, Hort J, Prins ND, Sheardova K, Kesslak P, Shen L, Zhu X, Albayrak A, Paul J, Schaefer JF, Power A, Tolar M. Effects of Oral ALZ-801/Valiltramiprosate on Plasma Biomarkers, Brain Hippocampal Volume, and Cognition: Results of 2-Year Single-Arm, Open-Label, Phase 2 Trial in APOE4 Carriers with Early Alzheimer's Disease. Drugs. 2024 Jul;84(7):811-823. doi: 10.1007/s40265-024-02067-8. Epub 2024 Jun 20.

  PMID: 38902571 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

ALZ-801

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• John Hey, PhD

  Alzheon Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2020
• First Posted: January 5, 2021
• Study Start: September 30, 2020
• Primary Completion: June 20, 2023
• Study Completion: July 16, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

CZ (3); NL (3)