Early Alzheimer's DiseasePhase 3APOLLOE4NCT04770220
An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early AD Subjects
A Phase 3 study testing Experimental: ALZ-801 in people with Early Alzheimer's Disease, run by Alzheon Inc. at 95 sites in 9 countries.
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. Read more about this study
- Who is it for?
- Ages 50 to 80 years
- Conditions the study is for
- Early Alzheimer's Disease
- What is being tested?
- Experimental: ALZ-801
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 325 participants
- Where
- 95 sitesin 9 countries
- Study dates
- 19 May 2021to 29 Jul 2024
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
95 sites in 9 countries.
95 sites in 9 countries
United States55 sites
Abington Neurological Associates
Abington, Pennsylvania, 19001
Neurological Associates of Albany
Albany, New York, 12208
Lehigh Center for Clinical Research
Allentown, Pennsylvania, 18104
JEM Research Institute, Headlands Site
Atlantis, Florida, 33462
Northwest Clinical Research Center
Bellevue, Washington, 98007
Bradenton Research Center
Bradenton, Florida, 34205
NeuroScience Research Center
Canton, Ohio, 44718
Columbus Memory Center
Columbus, Georgia, 31909
ATP Clinical Research
Costa Mesa, California, 92626
Neurology Diagnostics, Inc.
Dayton, Ohio, 45459
Sandhill Research, LLC
Decatur, Georgia, 30030
Rhode Island Mood & Memory Research Institute
East Providence, Rhode Island, 02914
Re:Cognition Health
Fairfax, Virginia, 22031
Fort Wayne Neurological Center
Fort Wayne, Indiana, 46804
Triad Clinical Trials
Greensboro, North Carolina, 27410
Galiz Research
Hialeah, Florida, 33016
UT Health Science Center at Houston
Houston, Texas, 77054
Tilda Research
Irvine, California, 92780
Alphab Global Research
Jupiter, Florida, 33458
UCSD Shiley-Marcos Alzheimer's Disease Research Center
La Jolla, California, 92037
Charter Research
Lady Lake, Florida, 32159
WR-CRCN
Las Vegas, Nevada, 89106
Torrance Clinical Research Institute
Lomita, California, 90717
Collaborative NeuroScience Network LLC
Long Beach, California, 90806
K2 Medical Research, LLC
Maitland, Florida, 32751
AMC Research
Matthews, North Carolina, 28105
Miami Jewish Health
Miami, Florida, 33137
Y & L Advance Health Care, Inc /DBA Elite Clinical Research
Miami, Florida, 33144
Mount Sinai Medical Center
Miami Beach, Florida, 33140
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Aqualane Clinical Research
Naples, Florida, 34105
Vanderbilt Center for Cognitive Medicine
Nashville, Tennessee, 37212
NYU Alzheimer's Disease Research Center
New York, New York, 10016
IPS Research
Oklahoma City, Oklahoma, 73106
Kline Institute for Psychiatric Research
Orangeburg, New York, 10962
Charter Research
Orlando, Florida, 32803
Headlands Research Orlando
Orlando, Florida, 32819
Advanced Research Consultants
Palm Beach Gardens, Florida, 33410
Stanford University
Palo Alto, California, 94304
SC3 Research Group
Pasadena, California, 91105
Xenoscience
Phoenix, Arizona, 85004
Headlands Research Eastern MA
Plymouth, Massachusetts, 02360
Quantum CNS Clinical Research
Pompano Beach, Florida, 33064
Progressive Medical Research
Port Orange, Florida, 32127
Center for Cognitive Health
Portland, Oregon, 97225
University of Rochester Medical Center
Rochester, New York, 14620
Sutter Health
Sacramento, California, 95816
CCT Research
Scottsdale, Arizona, 85297
Louisiana State University Health Sciences Center (LSUHSC)
Shreveport, Louisiana, 71103
Richmond Behavioral Associates
Staten Island, New York, 10312
ALZ Research and Treatment Center (A.R.T.C.)
Stuart, Florida, 34997
Banner Sun Health Research Institute
Sun City, Arizona, 85351
Advanced Memory Research Center
Toms River, New Jersey, 08755
ALZ Research and Treatment Center (A.R.T.C.)
Wellington, Florida, 33414
Premiere Research Institute
West Palm Beach, Florida, 33407
United Kingdom8 sites
Re-Cognition Health Ltd Birmingham
Birmingham, West Midlands, B16 8LT
Re:Cognition Health Ltd Bristol
Bristol, BS32 4SY
Re-Cognition Health Ltd Guildford
Guildford, Surrey, GU2 7YD
Re-Cognition Health Ltd London
London, Greater London, W1G 9JF
St. Pancras Clinical Research
London, EC2Y 8EA
NeuroClin Glasgow Ltd
Motherwell, North Lanarkshire, ML1 4UF
Re-Cognition Health Ltd Plymouth
Plymouth, Devon, PL6 8BT
Re-Cognition Health Ltd Winchester
Winchester, SO21 1HU
Canada7 sites
Recherches Neuro-Hippocampe Inc. d/b/a Clinique de la Mémoire de l'Outaouais
Gatineau, Quebec, J8T 8J1
Centricity Research
Halifax, Nova Scotia, B3S 1N2
OCT Research ULC (dba Okanagan Clinical Trials)
Kelowna, British Columbia, V1Y 1Z9
Centricity Research
New Minas, Nova Scotia, B4N 3R7
Recherches Neuro-Hippocampe Inc., d/b/a Ottawa Memory Clinic
Ottawa, Ontario, K1Z 1G3
Kawartha Centre - Redefining Healthy Aging
Peterborough, Ontario, K9H 2P4
Toronto Memory Program
Toronto, Ontario, M3B 2S7
France7 sites
Centre Hospitalier Universitaire de Marseille - Hôpital de la Timone
Marseille, 13385
Hopital Gui de Chauliac - CHRU de Montpellier
Montpellier, 43431
Hopital Lariboisiere - Fernand-Widal - AP-HP
Paris, 75475
Centre Hospitalier Universitaire (CHU) Hopitaux de Rouen
Rouen, 76031
Hopitaux Universitaires de Strasbourg Centre d'Investigation Clinique
Strasbourg, 67200
Centre de Recherche Clinique du Gerontopole - CHU Toulouse
Toulouse, 31059
Centre de Recherche-Hopital Geriatrique de Charpennes
Villeurbanne, 69100
Spain6 sites
Fundacia ACE - Institut Catala de Neurociencies Aplicadas
Barcelona, 08028
Clinica Universidad de Navarra
Madrid, 28027
Hospital Clinico San Carlos
Madrid, 28040
Clinica Universidad de Navarra
Pamplona, 31008
Hospital Universitari MutuaTerrassa
Terrassa, 08221
Centro Hospital Universitario Dr. Preset
Valencia, 46017
Czechia4 sites
Medica 111, Spol. s r.o. - Neurologicka a Rehabilitacni Ambulance Brno, Centralni Pracoviste v Brne
Brno, 602 00
Fakultní nemocnice u sv. Anny v Brně (St. Anne's University Hospital)
Brno, 656 91
Neuropsychiatrie s.r.o.
Prague, 160 00
Vestra Clinics - Dedicated Research Clinics
Rychnov nad Kněžnou, 51601
Germany4 sites
University Hospital RWTH Aachen Neurological Study Center
Aachen, 52074
Klinikum der Universitaet Muenchen Innenstadt
München, 80336
Universitätsklinik fuer Psychiatrie und Psychotherapie
Tübingen, 72076
Studienzentrum Nord-West
Westerstede, 26655
Netherlands3 sites
Brain Research Center Den Bosch
's-Hertogenbosch, 5223 LA
Brain Research Center Amsterdam
Amsterdam, 1081 GN
Brain Research Center Zwolle
Zwolle, 8025 AZ
About this study
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
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.
Read the 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.
- Conditions
- Early Alzheimer's Disease
- Being tested
- Experimental: ALZ-801, Placebo Comparator: Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental: ALZ-801Drug
Also called valiltramiprosate, tramiprosate prodrug
ALZ-801 tablet 265 mg once daily in the evening for the first 2 weeks, then ALZ-801 tablet 265 mg BID
Placebo Comparator: PlaceboDrug
Placebo tablet BID
| Study group | Role | What they receive |
|---|---|---|
| ALZ-801 | Experimental | ALZ-801 265 mg BID tablet orally. Subjects will receive placebo in the morning and one tablet of ALZ-801 265 mg tablet in the evening during the first two weeks of the study; thereafter, they will receive a 265 mg tablet twice daily (BID). Receives: Drug: Experimental: ALZ-801; Drug: Placebo Comparator: Placebo |
| Placebo | Placebo comparator | Subjects in the placebo treatment arm will receive placebo tablets BID throughout the study Receives: Drug: Placebo Comparator: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Cognitive Efficacy Endpoint (ADAS-Cog13)
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.
Measured: Baseline to Week 78
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 TEAEs, and TEAEs leading to withdrawal.
Measured: 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)
Secondary outcomes (4)
Key Secondary Endpoint (A-IADL-W)
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.
Measured: Baseline to Week 78
Key Secondary Endpoint (CDR-SB)
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.
Measured: Baseline to Week 78
Functional Assessment (DAD)
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.
Measured: Baseline to Week 78
Global Cognition Assessment (MMSE)
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.
Measured: Baseline to Week 78
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2021
- Study start19 May 2021
- Primary completion29 May 2024
- Study completion29 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Early Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a multi-center Phase 3, randomized, double-blind, placebo-controlled, parallel-group study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 325 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alzheon Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Susan Abushakra, MD, Principal investigator, Alzheon Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04770220
- Sponsor's protocol ID
- ALZ-801-AD301
- Other IDs
- R01AG065253, 2020-005755-20
- Acronym
- APOLLOE4
- Status last verified
- Sep 2026
- First submitted
- 22 Feb 2021
- Last updated
- 29 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hey JA, Abushakra S, Power A, Watson D, Porsteinsson A, Sabbagh M, MacSweeney E, Cohen S, Boada M, Doraiswamy PM, Elahi FM, Rissman RA, Liang E, Flint S, Hristova E, Kesslak P, McLaine R, Albayrak A, Schaefer JF, Yu JY, Tolar L, Tolar M. Plasma Biomarker Effects of Oral Valiltramiprosate/ALZ-801 in Early Alzheimer's Disease from Phase 3 and Phase 2 Trials: Analysis of Core Biomarkers and Correlations with Clinical and Neuroimaging Outcomes. Drugs. 2026 Sep 1. doi: 10.1007/s40265-026-02381-3. Online ahead of print.
PubMed 42678603Abushakra S, Power A, Watson D, Porsteinsson A, Sabbagh M, MacSweeney E, Cohen S, Boada Rovira M, Doraiswamy PM, Liang E, Flint S, Kesslak JP, McLaine R, Albayrak A, Schaefer J, Yu J, Tolar L, Dickson S, Hey JA, Tolar M. Clinical Efficacy, Safety and Imaging Effects of Oral Valiltramiprosate in APOEepsilon4/epsilon4 Homozygotes with Early Alzheimer's Disease: Results of the Phase III, Randomized, Double-Blind, Placebo-Controlled, 78-Week APOLLOE4 Trial. Drugs. 2025 Nov;85(11):1455-1472. doi: 10.1007/s40265-025-02250-5. Epub 2025 Sep 28.
PubMed 41015981