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
NCT ID: NCT04468659
Last Updated: 2026-01-12
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
1400 participants
INTERVENTIONAL
2020-07-14
2031-01-16
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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A45 Trial: Lecanemab 5 mg/kg + 10 mg/kg (Core Study)
Participants 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.
Lecanemab
IV infusion.
A45 Trial: Placebo (Core Study)
Participants 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.
Placebo
IV infusion.
A3 Trial: Lecanemab 5 mg/kg + 10 mg/kg (Core Study)
Participants 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.
Lecanemab
IV infusion.
A3 Trial: Placebo (Core Study)
Participants will receive placebo (0.9% sodium chloride solution), administered as IV infusion, every four weeks from Week 0 to 216.
Placebo
IV infusion.
A3 and A45 Trial: Lecanemab 10 mg/kg (Extension Phase)
Participants (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.
Lecanemab
IV infusion.
Interventions
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Lecanemab
IV infusion.
Placebo
IV infusion.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. 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
2. Global Clinical Dementia Rating (CDR) score of 0 at screening
3. Mini Mental State Examination score greater than or equal to (\>=) 27 (with educational adjustments) at screening.
4. Wechsler Memory Scale-Revised Logical Memory subscale II (WMS-R LM II) score at screening of \>=6
5. 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
6. 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
7. Provide written (or electronic, if allowed per country-specific regulations) informed consent
8. Willing and able to comply with all aspects of the protocol
For extension phase :
1. Completed the Core Study, or meet the following progression criteria during the Core Study:
* Two consecutive CDR visits with Global Scores \> zero when measured at least 6 months apart within the Core Study
* The principal investigator's confirmation that the participant has clinically declined consistent progression to EAD
2. Must continue to have a study partner who is willing and able to provide follow-up information on the participant throughout the course of the Extension Phase. The study partner must provide separate written informed consent for the Extension Phase. Study partners must continue to have sufficient contact such that the investigator feels the study partner can provide meaningful information about the participant's daily functions
3. Provide written informed consent for the Extension Phase. If a participant lacks capacity to consent in the investigator's opinion, the participant's assent should be obtained, if required and in accordance with local laws, regulations, and customs, plus the written informed consent of a legal representative (capacity to consent and the definition of a legal representative should be determined in accordance with applicable local laws and regulations). In countries where local laws, regulations, and customs do not permit participants who lack capacity to consent to participate in this study (example, Spain), they will not be enrolled
4. Willing and able to comply with all aspects of the protocol
Exclusion Criteria
1. Females who are breastfeeding or pregnant at screening or baseline
2. 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
3. History of transient ischemic attacks (TIA), stroke, or seizures within 12 months of screening
4. 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
5. 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
6. Hypersensitivity to any monoclonal antibody treatment
7. 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
8. Bleeding disorder that is not under adequate control (including a platelet count \<50,000 or international normalized ratio \[INR\] \>1.5) at screening
9. Results of laboratory tests conducted during screening that are outside the following limits:
* Thyroid stimulating hormone (TSH) above normal range
* Abnormally low (below lower limit of normal \[LLN\]) serum vitamin B12 levels for the testing laboratory (if participant is taking vitamin B12 injections, level should be at or above the LLN for the testing laboratory). A low vitamin B12 is exclusionary, unless the required follow-up labs (homocysteine and methylmalonic acid \[MMA\]) indicate that it is not physiologically significant
10. Known to be human immunodeficiency virus (HIV) positive
11. 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
12. 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. Answer "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, or any suicidal behavior assessment within 6 months before screening, at screening, or at baseline, or has been hospitalized or treated for suicidal behavior in the past 5 years before screening
14. Known or suspected history of drug or alcohol abuse or dependence within 2 years before screening or a positive urine drug test at screening. Participants who test positive for benzodiazepines, opioids, or tetrahydrocannabinol (THC) in urine drug testing need not be excluded unless in the clinical opinion of the investigator this is due to potential drug abuse
15. Taking prohibited medications
16. Participation in a clinical study involving:
* Any anti-amyloid plaque lowering immunotherapy (example, therapeutic monoclonal antibody or active anti-amyloid vaccine) at any time, unless it can be documented that the participant was randomized to placebo or never received study drug
* Any immunoglobulin therapy, or vaccine within 6 months before Screening, unless it can be documented that the participant was randomized to placebo or never received study drug
* Lecanemab
* Any new chemical entities or investigational drug for AD within 6 months before randomization unless it can be documented that the participant received only placebo
* Any other investigational medication or device study in the 8 weeks or 5 half-lives (whichever is longer) of the medication before randomization unless it can be documented that the participant was in a placebo treatment arm
17. Planned surgery during the pre-randomization phase or within 3 months of randomization, which requires general anesthesia
For extension phase:
1. Discontinued from the Core Study or from study treatment
2. Under study drug interruption due to ARIA or other AE at the time of transition to the extension phase
55 Years
80 Years
ALL
No
Sponsors
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Alzheimer's Clinical Trials Consortium
OTHER
Biogen
INDUSTRY
National Institute on Aging (NIA)
NIH
Eisai Inc.
INDUSTRY
Responsible Party
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Locations
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University of Alabama, Birmingham
Birmingham, Alabama, United States
Banner Alzheimer's Institute
Phoenix, Arizona, United States
Banner Sun Health Research Institute
Sun City, Arizona, United States
UCI MIND
Irvine, California, United States
University of Southern California
Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
Stanford University
Palo Alto, California, United States
Sharp Mesa Vista Hospital
San Diego, California, United States
Univeristy of California, San Francisco
San Francisco, California, United States
University of California, Davis
Walnut Creek, California, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Georgetown University
Washington D.C., District of Columbia, United States
Howard University
Washington D.C., District of Columbia, United States
Advanced Clinical Research Network, Corp
Coral Gables, Florida, United States
Brain Matters Research
Delray Beach, Florida, United States
Mayo Clinic Jacksonville
Jacksonville, Florida, United States
K2 Medical Research - The Villages
Lady Lake, Florida, United States
K2 Medical Research, Llc
Maitland, Florida, United States
K2 Medical Research
Maitland, Florida, United States
Gonzalez MD & Aswad MD Health Sciences
Miami, Florida, United States
Wien Center for Clinical Research
Miami Beach, Florida, United States
Renstar Medical Research
Ocala, Florida, United States
Synexus Clinical Research
Orlando, Florida, United States
University of South Florida - Health Byrd Alzheimer Institute
Tampa, Florida, United States
Synexus Clinical Research
The Villages, Florida, United States
Alzheimer's Research and Treatment Center
Wellington, Florida, United States
Charter Research
Winter Park, Florida, United States
Emory University
Atlanta, Georgia, United States
Columbus Memory Center, PC
Columbus, Georgia, United States
Northwestern University
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
Indiana University School of Medicine
Indianapolis, Indiana, United States
University of Kansas
Fairway, Kansas, United States
University of Kentucky
Lexington, Kentucky, United States
Johns Hopkins University
Baltimore, Maryland, United States
Boston University
Boston, Massachusetts, United States
Brigham and Woman's Hospital Center for Alzheimer Research and Treatment
Boston, Massachusetts, United States
Donald S.Marks, M.D.,P.C.
Plymouth, Massachusetts, United States
University of Michigan (UMICH)
Ann Arbor, Michigan, United States
Mayo Clinic, Rochester
Rochester, Minnesota, United States
Washington University
St Louis, Missouri, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, United States
Advanced Memory Research Institute of New Jersey
Toms River, New Jersey, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Columbia University
New York, New York, United States
University of Rochester
Rochester, New York, United States
Duke Health Center
Durham, North Carolina, United States
AMC Research
Matthews, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Case Western Reserve University/University Hospitals
Beachwood, Ohio, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
Cleveland, Ohio, United States
Ohio State University
Columbus, Ohio, United States
Central States Research, LLC
Tulsa, Oklahoma, United States
Summit Research Network, Oregon
Portland, Oregon, United States
Oregon Health & Science University
Portland, Oregon, United States
Abington Neurological Associates
Abington, Pennsylvania, United States
Keystone Clinical Studies, LLC
Norristown, Pennsylvania, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Butler Hospital Memory and Aging Program
Providence, Rhode Island, United States
Ralph H. Johnson VA Medical Center
Charleston, South Carolina, United States
Ralph H. Johnson VA Medical Center
Charleston, South Carolina, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
University of Texas, Southwestern MC at Dallas
Dallas, Texas, United States
University of North Texas Health Sciences Center
Fort Worth, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
Houston Methodist Neurological Institute
Houston, Texas, United States
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Eastern Virginia Medical School
Norfolk, Virginia, United States
National Clinical Research, Inc
Richmond, Virginia, United States
University of Washington Memory and Brain Wellness Center
Seattle, Washington, United States
SIBCR
Seattle, Washington, United States
University of Wisconsin
Madison, Wisconsin, 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 Memory Trials
Adelaide, South Australia, Australia
Austin Hospital - Medical and Cognitive Research Unit
Ivanhoe, Victoria, Australia
Alzheimer's Research Australia
Nedlands, Western Australia, Australia
Centricity Research
Hailfax, Nova Scotia, Canada
True North Clinical Research Inc.
New Minas, Nova Scotia, Canada
True North Clinical Research
New Minas, Nova Scotia, Canada
Parkwood Institute Main Building
London, Ontario, Canada
Toronto Memory Program
Toronto, Ontario, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
National Center for Geriatrics and Gerontology
Obu-shi, Aichi-ken, Japan
Fukuoka University Hospital
Fukuoka, Fukuoka, Japan
Kobe University Hospital
Kobe, Hyōgo, Japan
Shonan Kamakura General Hospital
Kamakura-shi, Kanagawa, Japan
Koseikai Takeda Hospital
Kyoto, Kyoto, Japan
Tohoku University Hospital
Sendai, Miyagi, Japan
Medical Corporation Heishinkai OPHAC Hospital
Osaka, Osaka, Japan
Medical Corporation Heishinkai OPHAC Hospital
Suita-shi, Osaka, Japan
The University of Tokyo Hospital
Bunkyo-ku, Tokyo, Japan
P-One Clinic, Keikokai Medical Corporation
Hachioji -shi, Tokyo, Japan
Tokyo Metropolitan Geriatric Hospital
Itabashi-ku, Tokyo, Japan
National Center of Neurology and Psychiatry
Kodaira-shi, Tokyo, Japan
ICR Clinical Research Hospital Tokyo
Shinjuku-Ku, Tokyo, Japan
National University Hospital
Singapore, , Singapore
Barcelona Beta Brain Research Center
Barcelona, , Spain
Fundació ACE
Barcelona, , Spain
Fundacion CITA ALZHEIMER
Donostia / San Sebastian, , Spain
Hospital Universitario Quirón Salud Madrid
Madrid, , Spain
Hospital Universitario Marqués de Valdeciila
Santander, , Spain
Bristol Brain Centre
Bristol, , United Kingdom
Glasgow Memory Clinic
Glasgow, , United Kingdom
St Pancras Clinical Research
London, , United Kingdom
Imperial Memory Unit
London, , United Kingdom
Countries
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References
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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.
Molina-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.
Rissman 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.
Kirn 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.
Other Identifiers
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