AHEAD 3-45 Study: A Study to Evaluate Efficacy and Safety of Treatment With Lecanemab in Participants With Preclinical Alzheimer's Disease and Elevated Amyloid and Also in Participants With Early Preclinical Alzheimer's Disease and Intermediate Amyloid
AHEAD 3-45 Study: A Placebo-Controlled, Double-Blind, Parallel-Treatment Arm, 216 Week Study With an Extension Phase to Evaluate Efficacy and Safety of Treatment With BAN2401 in Subjects With Preclinical Alzheimer's Disease and Elevated Amyloid (A45 Trial) and in Subjects With Early Preclinical Alzheimer's Disease and Intermediate Amyloid (A3 Trial)
4 other identifiers
interventional
1,400
7 countries
107
Brief Summary
The primary purpose of this study is to determine whether treatment with lecanemab is superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment (A45 Trial) and to determine whether treatment with lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by amyloid positron emission tomography (PET) at 216 weeks of treatment (A3 Trial). This study will also evaluate the long-term safety and tolerability of lecanemab in participants enrolled in the Extension Phase.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2020
Longer than P75 for phase_3
107 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 9, 2020
CompletedFirst Posted
Study publicly available on registry
July 13, 2020
CompletedStudy Start
First participant enrolled
July 14, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 21, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 16, 2031
March 13, 2026
December 1, 2025
8.4 years
July 9, 2020
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
A45 Trial: Change From Baseline in Preclinical Alzheimer Cognitive Composite 5 (PACC5) Score at Week 216
PACC5(5 components):Free/cued selective reminding test:number of words recalled without cuing/with cuing(0\[worst\]-96\[best recall\]);Delayed Paragraph Recall test: recall of 1 short story(25 bits information),immediately after reading and again after delay of 30 minutes (0\[worst\]-25\[best recall\]);Digit-symbol substitution test: Participant uses a key to fill in blank squares as fast as possible in 90 seconds(0\[none\]-91\[best performance\]);Mini Mental State Score:to evaluate orientation,memory,attention,concentration,naming,repetition,comprehension and ability to create sentence,to copy 2 overlapping pentagons, scored as number of correctly completed items(0\[worse\]-30\[perfect performance\]);Category fluency task: participants generate words in 60 second belonging to a semantic category(total score:number of appropriate words generated per task, higher values indicate better performance).
Baseline, Week 216
A3 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216
Baseline, Week 216
Secondary Outcomes (4)
A45 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Weeks 96 and 216
Baseline, Week 96, Week 216
A45 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Weeks 96 and 216
Baseline, Week 96, Week 216
A45 Trial: Change From Baseline in Cognitive Function Index (CFI) at Week 216
Baseline, Week 216
A3 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216
Baseline, Week 216
Study Arms (5)
A45 Trial: Lecanemab 5 mg/kg + 10 mg/kg (Core Study)
EXPERIMENTALParticipants will receive lecanemab 5 milligram per kilogram (mg/kg), administered as intravenous (IV) infusion, every two weeks from Week 0 to 6, then 10 mg/kg, administered as IV infusion, every two weeks from Week 8 to 94, and 10 mg/kg, administered as IV infusion, every four weeks from Week 96 to 216 in core study.
A45 Trial: Placebo (Core Study)
PLACEBO COMPARATORParticipants will receive placebo (0.9 percent \[%\] sodium chloride solution), administered as IV infusion, every two weeks from Week 0 to 94, then every four weeks from Week 96 to 216.
A3 Trial: Lecanemab 5 mg/kg + 10 mg/kg (Core Study)
EXPERIMENTALParticipants will receive lecanemab 5 mg/kg, administered as IV infusion, every four weeks from Week 0 to 4, then 10 mg/kg, administered as IV infusion, every four weeks from Week 8 to 216 in core study.
A3 Trial: Placebo (Core Study)
PLACEBO COMPARATORParticipants will receive placebo (0.9% sodium chloride solution), administered as IV infusion, every four weeks from Week 0 to 216.
A3 and A45 Trial: Lecanemab 10 mg/kg (Extension Phase)
EXPERIMENTALParticipants (from either A3 or A45 Trial) progressing to early Alzheimer's disease (EAD) during the core study (progressors) will receive lecanemab 10 mg/kg, administered as IV infusion, every two weeks after transition to the extension phase for at least 216 weeks from randomization in the core study. Participants completing the core study (completers) will enter extension phase and will receive lecanemab 5 mg/kg for initial 4 doses, than 10 mg/kg, administered as IV infusion, every two weeks for up to 96 weeks in extension phase.
Interventions
Eligibility Criteria
You may qualify if:
- Participants must meet all of the following criteria to be included in this study:
- Male or female, age 55 to 80 years inclusive at the time of informed consent, with a plasma biomarker result that is predictive of intermediate or elevated brain amyloid at Screening or known before Screening to have elevated or intermediate amyloid according to previous PET, cerebrospinal fluid (CSF), or plasma testing
- Those 55 to 64 must have 1 of the following additional risk factors, given the relatively low rates of amyloid positivity less than (\<) 65 years, before screening:
- First degree relative diagnosed with dementia onset before age 75, or
- Known to possess at least 1 apolipoprotein E4 variant (APOE4) allele, or
- Known before screening to have elevated brain amyloid according to previous plasma biomarker results, PET imaging, or CSF testing
- Global Clinical Dementia Rating (CDR) score of 0 at screening
- Mini Mental State Examination score greater than or equal to (\>=) 27 (with educational adjustments) at screening.
- Wechsler Memory Scale-Revised Logical Memory subscale II (WMS-R LM II) score at screening of \>=6
- A45 Trial: Elevated brain amyloid pathology by amyloid PET: defined as approximately greater than (\>) 40 Centiloids on screening scan A3 Trial: Intermediate levels of brain amyloid pathology by amyloid PET: defined as approximately 20 to 40 Centiloids on screening scan
- Has a study partner that is willing to participate as a source of information and has approximately weekly contact with the participant (contact can be in-person, via telephone or electronic communication). The study partner must have sufficient contact such that the investigator feels the study partner can provide meaningful information about the participant's daily function
- Provide written (or electronic, if allowed per country-specific regulations) informed consent
- Willing and able to comply with all aspects of the protocol
- For extension phase :
- Completed the Core Study, or meet the following progression criteria during the Core Study:
- +5 more criteria
You may not qualify if:
- Participants who meet any of the following criteria will be excluded from this study:
- Females who are breastfeeding or pregnant at screening or baseline
- Females of childbearing potential who:
- Within 28 days before study entry, did not use a highly effective method of contraception For sites outside of Europe, it is permissible that if a highly effective method of contraception is not appropriate or acceptable to the participant, then the participant must agree to use a medically acceptable method of contraception
- History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of screening
- Current or history within the past 2 years of psychiatric diagnosis or symptoms that, in the opinion of the investigator, could interfere with study procedures
- Contraindications to 3 Tesla magnetic resonance imaging (MRI) scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (example, in-skull and cardiac devices other than those approved as safe for use in MRI scanners), or exhibit other significant pathological findings on brain MRI at Screening
- Hypersensitivity to any monoclonal antibody treatment
- Any immunological disease which is not adequately controlled, or which requires treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives of monoclonal antibodies), systemic immunosuppressants, or plasmapheresis during the study
- Bleeding disorder that is not under adequate control (including a platelet count \<50,000 or international normalized ratio \[INR\] \>1.5) at screening
- Results of laboratory tests conducted during screening that are outside the following limits:
- Thyroid stimulating hormone (TSH) above normal range
- Known to be human immunodeficiency virus (HIV) positive
- Any other clinically significant abnormalities that in the opinion of the investigator require further investigation or treatment or may interfere with study procedures or safety
- Malignant neoplasms within 3 years of screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants with treatment cycles completed at least 6 months before screening). Participants who had malignant neoplasms but who have had at least 3 years of documented uninterrupted remission before screening need not be excluded
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eisai Inc.lead
- Alzheimer's Clinical Trials Consortiumcollaborator
- Biogencollaborator
- National Institute on Aging (NIA)collaborator
Study Sites (107)
University of Alabama, Birmingham
Birmingham, Alabama, 35233, United States
Banner Alzheimer's Institute
Phoenix, Arizona, 85006, United States
Banner Sun Health Research Institute
Sun City, Arizona, 85351, United States
UCI MIND
Irvine, California, 92697-4285, United States
University of Southern California
Los Angeles, California, 90033, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663, United States
Stanford University
Palo Alto, California, 94304, United States
Sharp Mesa Vista Hospital
San Diego, California, 92123, United States
University of California, San Francisco
San Francisco, California, 94158, United States
University of California, Davis
Walnut Creek, California, 94598, United States
Yale University School of Medicine
New Haven, Connecticut, 06510, United States
Georgetown University
Washington D.C., District of Columbia, 20057, United States
Howard University
Washington D.C., District of Columbia, 20060, United States
Advanced Clinical Research Network, Corp
Coral Gables, Florida, 33134-1613, United States
Brain Matters Research
Delray Beach, Florida, 33445, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224, United States
K2 Medical Research - The Villages
Lady Lake, Florida, 32159, United States
K2 Medical Research, Llc
Maitland, Florida, 32751, United States
Gonzalez MD & Aswad MD Health Sciences
Miami, Florida, 33125, United States
Wien Center for Clinical Research
Miami Beach, Florida, 33140, United States
Renstar Medical Research
Ocala, Florida, 34470, United States
Synexus Clinical Research - Orlando
Orlando, Florida, 32806, United States
University of South Florida - Health Byrd Alzheimer Institute
Tampa, Florida, 33613, United States
Synexus Clinical Research - The Villages
The Villages, Florida, 32162, United States
Alzheimer's Research and Treatment Center
Wellington, Florida, 33414, United States
Charter Research
Winter Park, Florida, 31792, United States
Emory University
Atlanta, Georgia, 30329, United States
Columbus Memory Center
Columbus, Georgia, 31909, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush University Medical Center
Chicago, Illinois, 60612, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
University of Kansas
Fairway, Kansas, 66205, United States
University of Kentucky
Lexington, Kentucky, 40504, United States
Johns Hopkins University
Baltimore, Maryland, 21224, United States
Boston University
Boston, Massachusetts, 02118, United States
Brigham and Woman's Hospital Center for Alzheimer Research and Treatment
Boston, Massachusetts, 21155, United States
Donald S.Marks, M.D.,P.C.
Plymouth, Massachusetts, 02360, United States
University of Michigan
Ann Arbor, Michigan, 48105, United States
Mayo Clinic, Rochester
Rochester, Minnesota, 55905, United States
Washington University, St. Louis
St Louis, Missouri, 63108, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, 89106, United States
Advanced Memory Research Institute of New Jersey
Toms River, New Jersey, 08755, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Columbia University
New York, New York, 10032, United States
University of Rochester
Rochester, New York, 14620, United States
Duke Health Center
Durham, North Carolina, 27705, United States
AMC Research
Matthews, North Carolina, 28105, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Case Western Reserve University/University Hospitals
Beachwood, Ohio, 44122, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
Cleveland, Ohio, 44195, United States
Ohio State University
Columbus, Ohio, 43210, United States
Central States Research, LLC
Tulsa, Oklahoma, 74136, United States
Summit Research Network, Oregon
Portland, Oregon, 97210, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Abington Neurological Associates
Abington, Pennsylvania, 19001, United States
Keystone Clinical Studies, LLC
Norristown, Pennsylvania, 19403, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Butler Hospital Memory and Aging Program
Providence, Rhode Island, 02906, United States
Ralph H. Johnson VA Medical Center
Charleston, South Carolina, 20403, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37212, United States
University of Texas, Southwestern MC at Dallas
Dallas, Texas, 75390, United States
University of North Texas Health Sciences Center
Fort Worth, Texas, 76107, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
Houston Methodist Neurological Institute
Houston, Texas, 77030, United States
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229-3900, United States
Eastern Virginia Medical School
Norfolk, Virginia, 23507, United States
National Clinical Research, Inc
Richmond, Virginia, 23294, United States
University of Washington Memory and Brain Wellness Center
Seattle, Washington, 98104, United States
SIBCR
Seattle, Washington, 98108, United States
University of Wisconsin, Madison
Madison, Wisconsin, 53792, United States
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
CALHN Cognitive Neurology Clinical Trials
Adelaide, South Australia, Australia
Austin Hospital - Medical and Cognitive Research Unit
Ivanhoe, Victoria, Australia
Alzheimer's Research Australia
Nedlands, Western Australia, 06009, Australia
Centricity Research
Hailfax, Nova Scotia, B3S 1L8, Canada
True North Clinical Research Inc.
New Minas, Nova Scotia, B4N 3R7, Canada
True North Clinical Research
New Minas, Nova Scotia, B4N 3R7, Canada
Parkwood Institute Main Building
London, Ontario, N6C0A7, Canada
Toronto Memory Program
Toronto, Ontario, M3B 2S7, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
National Center for Geriatrics and Gerontology
Obu-shi, Aichi-ken, 474-8511, Japan
Fukuoka University Hospital
Fukuoka, Fukuoka, 814-0180, Japan
Kobe University Hospital
Kobe, Hyōgo, 650-0017, Japan
Shonan Kamakura General Hospital
Kamakura-shi, Kanagawa, 247-8533, Japan
Koseikai Takeda Hospital
Kyoto, Kyoto, 600-8558, Japan
Tohoku University Hospital
Sendai, Miyagi, 980-8574, Japan
Medical Corporation Heishinkai OPHAC Hospital
Osaka, Osaka, 532-0003, Japan
The University of Osaka Hospital
Suita-shi, Osaka, 565-0871, Japan
The University of Tokyo Hospital
Bunkyo-ku, Tokyo, 113-8655, Japan
P-One Clinic, Keikokai Medical Corporation
Hachioji -shi, Tokyo, 192-0071, Japan
Tokyo Metropolitan Institute for Geriatrics and Gerontology
Itabashi-ku, Tokyo, 173-0015, Japan
National Center of Neurology and Psychiatry
Kodaira-shi, Tokyo, 187-8551, Japan
ICR Clinical Research Hospital Tokyo
Shinjuku-Ku, Tokyo, 160-0004, Japan
National University Hospital
Singapore, Singapore
Barcelona Beta Brain Research Center (BBRC)
Barcelona, 08005, Spain
Fundaci ACE
Barcelona, 08028, Spain
Fundacion CITA ALZHEIMER
Donostia / San Sebastian, 20009, Spain
Hospital Universitario Quir n Salud Madrid
Madrid, 28223, Spain
Hospital Universitario Marqu s de Valdeciila
Santander, 39008, Spain
Bristol Brain Centre
Bristol, BS10 5NB, United Kingdom
Glasgow Memory Clinic
Glasgow, ML1 4UF, United Kingdom
St Pancras Clinical Research
London, EC2Y 8EA, United Kingdom
Imperial Memory Unit
London, W6 8RF, United Kingdom
Related Publications (4)
Devanarayan V, Doherty T, Charil A, Sachdev P, Ye Y, Murali LK, Llano DA, Zhou J, Reyderman L, Hampel H, Kramer LD, Dhadda S, Irizarry MC. Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease. Alzheimers Dement. 2024 Aug;20(8):5617-5628. doi: 10.1002/alz.14073. Epub 2024 Jun 28.
PMID: 38940656DERIVEDMolina-Henry DP, Raman R, Liu A, Langford O, Johnson K, Shum LK, Glover CM, Dhadda S, Irizarry M, Jimenez-Maggiora G, Braunstein JB, Yarasheski K, Venkatesh V, West T, Verghese PB, Rissman RA, Aisen P, Grill JD, Sperling RA. Racial and ethnic differences in plasma biomarker eligibility for a preclinical Alzheimer's disease trial. Alzheimers Dement. 2024 Jun;20(6):3827-3838. doi: 10.1002/alz.13803. Epub 2024 Apr 17.
PMID: 38629508DERIVEDRissman RA, Langford O, Raman R, Donohue MC, Abdel-Latif S, Meyer MR, Wente-Roth T, Kirmess KM, Ngolab J, Winston CN, Jimenez-Maggiora G, Rafii MS, Sachdev P, West T, Yarasheski KE, Braunstein JB, Irizarry M, Johnson KA, Aisen PS, Sperling RA; AHEAD 3-45 Study team. Plasma Abeta42/Abeta40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease. Alzheimers Dement. 2024 Feb;20(2):1214-1224. doi: 10.1002/alz.13542. Epub 2023 Nov 6.
PMID: 37932961DERIVEDKirn DR, Grill JD, Aisen P, Ernstrom K, Gale S, Heidebrink J, Jicha G, Jimenez-Maggiora G, Johnson L, Peskind E, McCann K, Shaffer E, Sultzer D, Wang S, Sperling R, Raman R. Centralizing prescreening data collection to inform data-driven approaches to clinical trial recruitment. Alzheimers Res Ther. 2023 May 2;15(1):88. doi: 10.1186/s13195-023-01235-4.
PMID: 37131229DERIVED
MeSH Terms
Interventions
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 9, 2020
First Posted
July 13, 2020
Study Start
July 14, 2020
Primary Completion (Estimated)
December 21, 2028
Study Completion (Estimated)
January 16, 2031
Last Updated
March 13, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will share
Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.