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

Early Alzheimer's Disease Clinical Trial

— APOLLOE4  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04770220
• Other study ID #: ALZ-801-AD301
• Secondary ID: R01AG0652532020-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 19, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: May 2024
• Source: Alzheon Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

This is a multi-center, double-blind study that will evaluate 265 mg 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: June 30, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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 e4 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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Early Alzheimer's Disease

Intervention

Drug:
• Experimental: ALZ-801
ALZ-801 tablet 265 mg BID
• Placebo Comparator: Placebo
Placebo tablet BID

Locations

Country	Name	City	State
Canada	Recherches Neuro-Hippocampe Inc. d/b/a Clinique de la Mémoire de l'Outaouais	Gatineau	Quebec
Canada	Centricity Research	Halifax	Nova Scotia
Canada	OCT Research ULC (dba Okanagan Clinical Trials)	Kelowna	British Columbia
Canada	Centricity Research	New Minas	Nova Scotia
Canada	Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic	Ottawa	Ontario
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	Toronto Memory Program	Toronto	Ontario
Czechia	Fakultní nemocnice u sv. Anny v Brne (St. Anne's University Hospital)	Brno
Czechia	Medica 111, Spol. s r.o. - Neurologicka a Rehabilitacni Ambulance Brno, Centralni Pracoviste v Brne	Brno
Czechia	Neuropsychiatrie s.r.o.	Praha
Czechia	Vestra Clinics - Dedicated Research Clinics	Rychnov Nad Knežnou
France	Centre Hospitalier Universitaire de Marseille - Hôpital de la Timone	Marseille
France	Hopital Gui de Chauliac - CHRU de Montpellier	Montpellier Cedex 5
France	Hopital Lariboisiere - Fernand-Widal - AP-HP	Paris Cedex 10
France	Centre Hospitalier Universitaire (CHU) Hopitaux de Rouen	Rouen
France	Hopitaux Universitaires de Strasbourg Centre d'Investigation Clinique	Strasbourg
France	Centre de Recherche Clinique du Gerontopole - CHU Toulouse	Toulouse
France	Centre de Recherche-Hopital Geriatrique de Charpennes	Villeurbanne
Germany	University Hospital RWTH Aachen Neurological Study Center	Aachen
Germany	Klinikum der Universitaet Muenchen Innenstadt	Muenchen
Germany	Universitätsklinik fuer Psychiatrie und Psychotherapie	Tuebingen
Germany	Studienzentrum Nord-West	Westerstede
Iceland	Memory Clinic, Landspitali University Hospital	Reykjavík
Netherlands	Brain Research Center Amsterdam	Amsterdam
Netherlands	Brain Research Center Den Bosch	Den Bosch
Netherlands	Brain Research Center Zwolle	Zwolle
Spain	Fundacia ACE - Institut Catala de Neurociencies Aplicadas	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Hospital Universitari MutuaTerrassa	Terrassa
Spain	Centro Hospital Universitario Dr. Preset	Valencia
United Kingdom	Re-Cognition Health Ltd Birmingham	Birmingham	West Midlands
United Kingdom	Re:Cognition Health Ltd Bristol	Bristol
United Kingdom	Re-Cognition Health Ltd Guildford	Guildford	Surrey
United Kingdom	Re-Cognition Health Ltd London	London	Greater London
United Kingdom	St. Pancras Clinical Research	London
United Kingdom	NeuroClin Glasgow Ltd	Motherwell	North Lanarkshire
United Kingdom	Re-Cognition Health Ltd Plymouth	Plymouth	Devon
United Kingdom	Re-Cognition Health Ltd Winchester	Winchester
United States	Abington Neurological Associates	Abington	Pennsylvania
United States	Neurological Associates of Albany	Albany	New York
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	JEM Research Institute, Headlands Site	Atlantis	Florida
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Bradenton Research Center	Bradenton	Florida
United States	NeuroScience Research Center	Canton	Ohio
United States	Columbus Memory Center	Columbus	Georgia
United States	ATP Clinical Research	Costa Mesa	California
United States	Neurology Diagnostics	Dayton	Ohio
United States	Accel Research Sites	Decatur	Georgia
United States	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island
United States	Re:Cognition Health	Fairfax	Virginia
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Triad Clinical Trials	Greensboro	North Carolina
United States	Galiz Research	Hialeah	Florida
United States	UT Health Science Center at Houston	Houston	Texas
United States	Alphab Global Research	Jupiter	Florida
United States	UCSD Shiley-Marcos Alzheimer's Disease Research Center	La Jolla	California
United States	Charter Research	Lady Lake	Florida
United States	Wake Research - Clinical Research Center of Nevada	Las Vegas	Nevada
United States	Torrance Clinical Research Institute	Lomita	California
United States	Collaborative NeuroScience Network LLC	Long Beach	California
United States	K2 Medical Research, LLC	Maitland	Florida
United States	AMC Research	Matthews	North Carolina
United States	Miami Jewish Health	Miami	Florida
United States	Y & L Advance Health Care, Inc /DBA Elite Clinical Research	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Aqualane Clinical Research	Naples	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	NYU Alzheimer's Disease Research Center	New York	New York
United States	IPS Research	Oklahoma City	Oklahoma
United States	Kline Institute for Psychiatric Research	Orangeburg	New York
United States	Charter Research	Orlando	Florida
United States	Headlands Research Orlando	Orlando	Florida
United States	Advanced Research Consultants	Palm Beach Gardens	Florida
United States	Stanford University	Palo Alto	California
United States	SC3 Research Group	Pasadena	California
United States	Xenoscience	Phoenix	Arizona
United States	Headlands Research Eastern MA	Plymouth	Massachusetts
United States	Quantum CNS Clinical Research	Pompano Beach	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Center for Cognitive Health	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	Sutter Health	Sacramento	California
United States	CCT Research	Scottsdale	Arizona
United States	Louisiana State University Health Sciences Center (LSUHSC)	Shreveport	Louisiana
United States	Richmond Behavioral Associates	Staten Island	New York
United States	ALZ Research and Treatment Center (A.R.T.C.)	Stuart	Florida
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	Advanced Memory Research Center	Toms River	New Jersey
United States	Tilda Research, Inc.	Tustin	California
United States	ALZ Research and Treatment Center (A.R.T.C.)	Wellington	Florida
United States	Premiere Research Institute	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Alzheon Inc.	National Institute on Aging (NIA)

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  France,  Germany,  Iceland,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary cognitive efficacy endpoint	Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-cog 13) scores at 78 weeks	Week 78
Primary	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 78
Primary	Primary fluid biomarker endpoint 1	Change from baseline in cerebrospinal fluid p-tau181 levels in sub-study	Week 78
Primary	Primary fluid biomarker endpoint 2	Change from baseline in plasma p-tau181 levels	Week 78
Primary	Primary imaging biomarker endpoint	Change from baseline in total hippocampal volume (mm3) as measured by Magnetic Resonance Imaging (MRI)	Week 78
Secondary	Functional assessment 1	Change from baseline in Amsterdam - Instrumental Activities of Daily Living scores	Week 78
Secondary	Global assessment	Change from baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) scores	Week 78
Secondary	Functional assessment 2	Change from baseline in Disability Assessment for Dementia (DAD)scores	Week 78