Clinical trial NCT04770220: An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early AD Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Early Alzheimer's Disease
Lead sponsor: Alzheon Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Aging (NIA)
First posted: 2021-02-25
Enrollment: 325
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multi-center Phase 3, randomized, double-blind, placebo-controlled, parallel-group study.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Primary cognitive efficacy endpoint
timeFrame: Week 78
measure: Incidence, Nature, and Severity of Treatment Emergent Adverse events (TEAE)
timeFrame: Week 78
Secondary outcomes:
measure: Functional assessment 1
timeFrame: Week 78
measure: Global assessment
timeFrame: Week 78
measure: Functional assessment 2
timeFrame: Week 78
Other outcomes:
measure: Fluid biomarker endpoint 1
timeFrame: Week 78
measure: Fluid biomarker endpoint 2
timeFrame: Week 78
measure: Imaging biomarker endpoint
timeFrame: Week 78
Locations:
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Scottsdale
country: United States
facility: CCT Research
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Costa Mesa
country: United States
facility: ATP Clinical Research
state: California
city: Irvine
country: United States
facility: Tilda Research
state: California
city: La Jolla
country: United States
facility: UCSD Shiley-Marcos Alzheimer's Disease Research Center
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute
state: California
city: Long Beach
country: United States
facility: Collaborative NeuroScience Network LLC
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Pasadena
country: United States
facility: SC3 Research Group
state: California
city: Sacramento
country: United States
facility: Sutter Health
state: California
city: Atlantis
country: United States
facility: JEM Research Institute, Headlands Site
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Hialeah
country: United States
facility: Galiz Research
state: Florida
city: Jupiter
country: United States
facility: Alphab Global Research
state: Florida
city: Lady Lake
country: United States
facility: Charter Research
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research, LLC
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health
state: Florida
city: Miami
country: United States
facility: Y & L Advance Health Care, Inc /DBA Elite Clinical Research
state: Florida
city: Naples
country: United States
facility: Aqualane Clinical Research
state: Florida
city: Orlando
country: United States
facility: Charter Research
state: Florida
city: Orlando
country: United States
facility: Headlands Research Orlando
state: Florida
city: Palm Beach Gardens
country: United States
facility: Advanced Research Consultants
state: Florida
city: Pompano Beach
country: United States
facility: Quantum CNS Clinical Research
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Stuart
country: United States
facility: ALZ Research and Treatment Center (A.R.T.C.)
state: Florida
city: Wellington
country: United States
facility: ALZ Research and Treatment Center (A.R.T.C.)
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Columbus
country: United States
facility: Columbus Memory Center
state: Georgia
city: Decatur
country: United States
facility: Sandhill Research, LLC
state: Georgia
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center (LSUHSC)
state: Louisiana
city: Plymouth
country: United States
facility: Headlands Research Eastern MA
state: Massachusetts
city: Las Vegas
country: United States
facility: WR-CRCN
state: Nevada
city: Toms River
country: United States
facility: Advanced Memory Research Center
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany
state: New York
city: New York
country: United States
facility: NYU Alzheimer's Disease Research Center
state: New York
city: Orangeburg
country: United States
facility: Kline Institute for Psychiatric Research
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Greensboro
country: United States
facility: Triad Clinical Trials
state: North Carolina
city: Matthews
country: United States
facility: AMC Research
state: North Carolina
city: Canton
country: United States
facility: NeuroScience Research Center
state: Ohio
city: Dayton
country: United States
facility: Neurology Diagnostics, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research
state: Oklahoma
city: Portland
country: United States
facility: Center for Cognitive Health
state: Oregon
city: Abington
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood & Memory Research Institute
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Center for Cognitive Medicine
state: Tennessee
city: Houston
country: United States
facility: UT Health Science Center at Houston
state: Texas
city: Fairfax
country: United States
facility: Re:Cognition Health
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Kelowna
country: Canada
facility: OCT Research ULC (dba Okanagan Clinical Trials)
state: British Columbia
city: Halifax
country: Canada
facility: Centricity Research
state: Nova Scotia
city: New Minas
country: Canada
facility: Centricity Research
state: Nova Scotia
city: Ottawa
country: Canada
facility: Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic
state: Ontario
city: Peterborough
country: Canada
facility: Kawartha Centre - Redefining Healthy Aging
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Gatineau
country: Canada
facility: Recherches Neuro-Hippocampe Inc. d/b/a Clinique de la Mémoire de l'Outaouais
state: Quebec
city: Brno
country: Czechia
facility: Medica 111, Spol. s r.o. - Neurologicka a Rehabilitacni Ambulance Brno, Centralni Pracoviste v Brne
city: Brno
country: Czechia
facility: Fakultní nemocnice u sv. Anny v Brně (St. Anne's University Hospital)
city: Praha
country: Czechia
facility: Neuropsychiatrie s.r.o.
city: Rychnov Nad Kněžnou
country: Czechia
facility: Vestra Clinics - Dedicated Research Clinics
city: Marseille
country: France
facility: Centre Hospitalier Universitaire de Marseille - Hôpital de la Timone
city: Montpellier Cedex 5
country: France
facility: Hopital Gui de Chauliac - CHRU de Montpellier
city: Paris Cedex 10
country: France
facility: Hopital Lariboisiere - Fernand-Widal - AP-HP
city: Rouen
country: France
facility: Centre Hospitalier Universitaire (CHU) Hopitaux de Rouen
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg Centre d'Investigation Clinique
city: Toulouse
country: France
facility: Centre de Recherche Clinique du Gerontopole - CHU Toulouse
city: Villeurbanne
country: France
facility: Centre de Recherche-Hopital Geriatrique de Charpennes
city: Aachen
country: Germany
facility: University Hospital RWTH Aachen Neurological Study Center
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen Innenstadt
city: Tuebingen
country: Germany
facility: Universitätsklinik fuer Psychiatrie und Psychotherapie
city: Westerstede
country: Germany
facility: Studienzentrum Nord-West
city: Reykjavík
country: Iceland
facility: Memory Clinic, Landspitali University Hospital
city: Amsterdam
country: Netherlands
facility: Brain Research Center Amsterdam
city: Den Bosch
country: Netherlands
facility: Brain Research Center Den Bosch
city: Zwolle
country: Netherlands
facility: Brain Research Center Zwolle
city: Barcelona
country: Spain
facility: Fundacia ACE - Institut Catala de Neurociencies Aplicadas
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Terrassa
country: Spain
facility: Hospital Universitari MutuaTerrassa
city: Valencia
country: Spain
facility: Centro Hospital Universitario Dr. Preset
city: Plymouth
country: United Kingdom
facility: Re-Cognition Health Ltd Plymouth
state: Devon
city: London
country: United Kingdom
facility: Re-Cognition Health Ltd London
state: Greater London
city: Motherwell
country: United Kingdom
facility: NeuroClin Glasgow Ltd
state: North Lanarkshire
city: Guildford
country: United Kingdom
facility: Re-Cognition Health Ltd Guildford
state: Surrey
city: Birmingham
country: United Kingdom
facility: Re-Cognition Health Ltd Birmingham
state: West Midlands
city: Bristol
country: United Kingdom
facility: Re:Cognition Health Ltd Bristol
city: London
country: United Kingdom
facility: St. Pancras Clinical Research
city: Winchester
country: United Kingdom
facility: Re-Cognition Health Ltd Winchester
Study officials:
affiliation: Alzheon Inc.
name: Susan Abushakra, MD
role: PRINCIPAL_INVESTIGATOR
References: