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
- Conditions
- Early Preclinical Alzheimer's DiseasePreclinical Alzheimer's Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT04468659
- Lead Sponsor
- Eisai Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 1400
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A45 Trial: Placebo (Core Study) Placebo 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. A3 Trial: Lecanemab 5 mg/kg + 10 mg/kg (Core Study) Lecanemab 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. A3 Trial: Placebo (Core Study) Placebo Participants will receive placebo (0.9% sodium chloride solution), administered as IV infusion, every four weeks from Week 0 to 216. A45 Trial: Lecanemab 5 mg/kg + 10 mg/kg (Core Study) Lecanemab 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. A45 Trial: Lecanemab 10 mg/kg (Extension Phase) Lecanemab Participants 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 through to at least Week 216 from randomization in the core study. Participants completing the core study (completers) will enter extension phase and will receive lecanemab 10 mg/kg, administered as IV infusion, every two weeks for up to Week 312. Eligible participants receiving placebo in core study will continue to extension phase. A3 Trial: Lecanemab 10 mg/kg (Extension Phase) Lecanemab Participants progressing to 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 through to at least Week 216 from randomization in the core study. Participants completing the core study (completers) will enter extension phase and will receive lecanemab 10 mg/kg, administered as IV infusion, every two weeks for up to Week 312. Eligible participants receiving placebo in core study will continue to extension phase.
- Primary Outcome Measures
Name Time Method A45 Trial: Change From Baseline in Preclinical Alzheimer Cognitive Composite 5 (PACC5) Score at Week 216 Baseline, 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).
A3 Trial: Change From Baseline in Amyloid Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 Baseline, Week 216
- Secondary Outcome Measures
Name Time Method 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 CFI assessment to assess the participant's perceived ability to perform high-level functional tasks in daily life and sense of overall cognitive functional ability. Study participants (18 questions) and their study partners (15 questions) independently rate the participant's abilities. Total score combines participant and study partner scores, with higher scores indicating greater impairment.
A3 Trial: Change From Baseline in tau Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at Week 216 Baseline, Week 216 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
Trial Locations
- Locations (105)
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, District of Columbia, United States
Howard University
🇺🇸Washington, 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
Wien Center for Clinical Research
🇺🇸Miami Beach, Florida, United States
Gonzalez MD & Aswad MD Health Sciences
🇺🇸Miami, Florida, United States
Renstar Medical Research
🇺🇸Ocala, Florida, United States
Synexus Clinical Research
🇺🇸The Villages, Florida, United States
University of South Florida - Health Byrd Alzheimer Institute
🇺🇸Tampa, 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
🇺🇸Saint Louis, Missouri, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
🇺🇸Cleveland, Ohio, 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
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
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, Japan
Fukuoka University Hospital
🇯🇵Fukuoka-shi, Fukuoka, Japan
Kobe University Hospital
🇯🇵Kobe-shi, Hyogo, Japan
Shonan Kamakura General Hospital
🇯🇵Kamakura-shi, Kanagawa, Japan
Koseikai Takeda Hospital
🇯🇵Kyoto-shi, Kyoto, Japan
Tohoku University Hospital
🇯🇵Sendai-shi, Miyagi, 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
Hospital Universitario Quirón Salud Madrid
🇪🇸Madrid, Spain
Fundacion CITA ALZHEIMER
🇪🇸San Sebastian, 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