Clinical trial NCT05026866: A Donanemab (LY3002813) Study in Participants With Preclinical Alzheimer's Disease (TRAILBLAZER-ALZ 3)
Official title: A Study of Donanemab Versus Placebo in Participants at Risk for Cognitive and Functional Decline of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Alzheimer Disease
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2021-08-30
Enrollment: 2996
Sex: ALL
Minimum age (years): 65
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety and efficacy of donanemab in participants with preclinical Alzheimer's Disease (AD). Approximately 800 additional participants will be enrolled in a 12-month addendum to assess safety of a different titration regimen.


Eligibility criteria: Inclusion Criteria:

* A Telephone Interview for Cognitive Status - modified (TICS-M) score reflective of intact cognitive functioning.
* Has a phosphorylated tau (P-tau) result consistent with the presence of amyloid and early-tau pathology.
* Has a reliable study partner and backup study partner familiar with overall function and behavior, such as day-to-day activities and cognitive abilities.
* Have adequate literacy, vision, and hearing for neuropsychological testing at screening.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
* Female participants include those who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis; or post menopausal (women 55 or older not on hormone therapy and had at least 12 months of spontaneous amenorrhea; or with a diagnosis of menopause prior to starting hormone replacement therapy.

Exclusion Criteria:

* Mild cognitive impairment or dementia, or significant other neurodegenerative disease that can affect cognition.
* Current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease that could interfere with the analysis of the study or a life expectancy of approximately ≤5 years.
* History of cancer with high risk of recurrence and preventing completion of the trial.
* History of clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions (including but not limited to erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, and/or exfoliative dermatitis).
* Have any clinically important abnormality at screening on magnetic resonance imaging (MRI) or clinical laboratory test results that could be detrimental to the participant or study integrity.
* Have any contraindications for MRI, including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker.
* Have a centrally read MRI demonstrating presence of amyloid-related imaging abnormalities (ARIA-E), \>4 cerebral microhemorrhages, more than 1 area of superficial siderosis, any macrohemorrhage or severe white matter disease at screening.
* Have had prior treatment with a passive anti-amyloid immunotherapy \<5 half-lives prior to randomization.
* Have received active immunization against amyloid beta (Aβ) in any other study.
* Have received active immunization against Aβ in any other study.
* Current or previous use of prescription medications used as treatment for mild cognitive impairment (MCI) or AD.

Addendum 7 Exclusion Criteria for Clinicaltrials.gov:

* Same as the main study except contraindications for florbetapir F 18 PET are exclusionary.

Primary outcomes:
measure: Time to clinical progression as measured by Clinical Dementia Rating - Global Score (CDR-GS)
timeFrame: Estimated Up to Week 182
Secondary outcomes:
measure: Change from Baseline in International Shopping List Test (ISLT)
timeFrame: Baseline, Up to Week 182
measure: Change from Baseline in Continuous Paired Associate Learning (CPAL)
timeFrame: Baseline, Up to Week 182
measure: Change from Baseline in International Daily Symbol Substitution Test-Medicines (iDSSTm)
timeFrame: Baseline, Up to Week 182
measure: Change from Baseline in Category Fluency
timeFrame: Baseline, Up to Week 182
measure: Change from Baseline in Face Name Association Test (FNAME)
timeFrame: Baseline, Up to Week 182
measure: Change from Baseline in Behavioral Pattern Separation-Object test (BPS-O)
timeFrame: Baseline, Up to Week 182
measure: Change from Baseline in Cogstate Brief Battery (CBB)
timeFrame: Baseline, Up to Week 182
measure: Change from Baseline in CDR-Sum of Boxes (CDR-SB)
timeFrame: Baseline, Up Week 32
measure: Change from Baseline in Cognitive Function Index (CFI)
timeFrame: Baseline, Up to Week 182
measure: Change from Baseline in Montreal Cognitive Assessment (MoCA) score
timeFrame: Baseline, Up to Week 182
measure: Pharmacokinetics (PK): Average Serum Donanemab Concentration at Steady State
timeFrame: Baseline through Week 76
measure: Percentage of Participants with Treatment-emergent Anti-Drug Antibody (ADAs)
timeFrame: Baseline through Week 16
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Parkway Medical Center
state: Alabama
city: Homewood
country: United States
facility: Alabama Psychiatry - Birmingham - Brookwood Medical Center Drive
state: Alabama
city: Huntsville
country: United States
facility: Rehabilitation & Neurological Services
state: Alabama
city: Mesa
country: United States
facility: Care Access - 801 South Power Road, Mesa
state: Arizona
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Tucson
country: United States
facility: Banner Alzheimer's Institute Tucson
state: Arizona
city: Tucson
country: United States
facility: Center for Neurosciences
state: Arizona
city: Berkeley
country: United States
facility: Care Access - Berkeley
state: California
city: Beverly Hills
country: United States
facility: Care Access - Beverly Hills
state: California
city: Chula Vista
country: United States
facility: Velocity Clinical Research, Chula Vista
state: California
city: Covina
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: Gilroy
country: United States
facility: Care Access - Gilroy
state: California
city: Huntington Beach
country: United States
facility: Care Access Research - Huntington Beach
state: California
city: Irvine
country: United States
facility: Irvine Clinical Research
state: California
city: Irvine
country: United States
facility: Option Care - Irvine
state: California
city: La Jolla
country: United States
facility: Kaizen Brain Center
state: California
city: La Mesa
country: United States
facility: Velocity Clinical Research, San Diego
state: California
city: Lemon Grove
country: United States
facility: Pacific Research Network
state: California
city: Long Beach
country: United States
facility: Healthy Brain Clinic
state: California
city: Napa
country: United States
facility: Neurovations
state: California
city: Newport Beach
country: United States
facility: Care Access - Newport Beach
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials, Inc.
state: California
city: Redlands
country: United States
facility: Inland Psychiatric Medical Group
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: Riverside
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Riverside
country: United States
facility: Option Care - Riverside
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: San Francisco
country: United States
facility: Ray Dolby Brain Health Center
state: California
city: San Jose
country: United States
facility: Care Access - Los Gatos
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Santa Clarita
country: United States
facility: Care Access - Santa Clarita
state: California
city: Santa Fe Springs
country: United States
facility: Option Care - Los Angeles South
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Foundation
state: California
city: Thousand Oaks
country: United States
facility: Mazur, Statner, Dutta, Nathan, PC
state: California
city: Tustin
country: United States
facility: Tilda Research
state: California
city: Van Nuys
country: United States
facility: Velocity Clinical Research, Panorama City
state: California
city: Walnut Creek
country: United States
facility: Infectious Disease Doctors Medical Group, APC
state: California
city: Aurora
country: United States
facility: Care Access - Aurora
state: Colorado
city: Basalt
country: United States
facility: Mountain Neurological Research Center
state: Colorado
city: Denver
country: United States
facility: Denver Neurological Research
state: Colorado
city: New Haven
country: United States
facility: Invicro
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Aventura
country: United States
facility: VIN-Julie Schwartzbard
state: Florida
city: Boca Raton
country: United States
facility: Neurology Offices of South Florida
state: Florida
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Boca Raton
country: United States
facility: SFM Clinical Research
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc.
state: Florida
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc. (Clearwater)
state: Florida
city: Daytona Beach
country: United States
facility: Care Access - Daytona Beach
state: Florida
city: Delray Beach
country: United States
facility: Care Access - Delray Beach
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Lady Lake
country: United States
facility: Care Access - Guava Street
state: Florida
city: Largo
country: United States
facility: Accel Research Sites - St. Pete-Largo Clinical Research Unit
state: Florida
city: Maitland
country: United States
facility: ClinCloud - Maitland
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research
state: Florida
city: Melbourne
country: United States
facility: ClinCloud - Viera
state: Florida
city: Merritt Island
country: United States
facility: Merritt Island Medical Research, LLC
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami Springs
country: United States
facility: South Florida Research Phase I-IV
state: Florida
city: Miami
country: United States
facility: Optimus U Corporation
state: Florida
city: Miami
country: United States
facility: Finlay Medical Research
state: Florida
city: Miami
country: United States
facility: VIN-Andrew Lerman
state: Florida
city: Miami
country: United States
facility: Brainstorm Research Group
state: Florida
city: Miami
country: United States
facility: IMIC, Inc.
state: Florida
city: Miami
country: United States
facility: VIN-Victor Faradji
state: Florida
city: Mount Dora
country: United States
facility: Adult Medicine of Lake County
state: Florida
city: New Port Richey
country: United States
facility: Suncoast Clinical Research, Inc.
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Charter Research - Winter Park
state: Florida
city: Orlando
country: United States
facility: Headlands Research Orlando
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center, LLC
state: Florida
city: Pembroke Pines
country: United States
facility: VIN- Margarita Almeida El-Ramey
state: Florida
city: Pensacola
country: United States
facility: Emerald Coast Neurology - Airport Boulevard
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Sun City Center
country: United States
facility: Care Access - Sun City Center - Cypress Village Boulevard
state: Florida
city: Tamarac
country: United States
facility: Care Access - Tamarac
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Tampa
country: United States
facility: K2 Medical Research - Tampa
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Tampa
country: United States
facility: Vicis Clinical Research
state: Florida
city: Tampa
country: United States
facility: Coram CVS/Specialty Infusion Services - Tampa
state: Florida
city: The Villages
country: United States
facility: Charter Research - Lady Lake
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Winter Park
country: United States
facility: Conquest Research
state: Florida
city: Augusta
country: United States
facility: Masters of Clinical Research
state: Georgia
city: Decatur
country: United States
facility: iResearch Atlanta
state: Georgia
city: Gainesville
country: United States
facility: Center for Advanced Research & Education
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research, LLC
state: Georgia
city: Union City
country: United States
facility: SKY Clinical Research Network Group-Blake
state: Georgia
city: Woodstock
country: United States
facility: North Georgia Clinical Research
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Chicago
country: United States
facility: IMA Clinical Research - Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: Great Lakes Clinical Trials - Andersonville
state: Illinois
city: Chicago
country: United States
facility: Uptown Research Institute
state: Illinois
city: Elk Grove Village
country: United States
facility: AMITA Health - Alexian Brothers Neurosciences Institute Clinical Research
state: Illinois
city: Fairview Heights
country: United States
facility: Care Access - Fairview Heights
state: Illinois
city: Gurnee
country: United States
facility: Great Lakes Clinical Trials - Gurnee
state: Illinois
city: Lombard
country: United States
facility: Accellacare - DuPage
state: Illinois
city: Fort Wayne
country: United States
facility: Coram CVS/Specialty Infusion Services - Fort Wayne
state: Indiana
city: Indianapolis
country: United States
facility: Care Access - South Indianapolis
state: Indiana
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology, PC
state: Indiana
city: Waterloo
country: United States
facility: Covenant Medical Center
state: Iowa
city: Overland Park
country: United States
facility: College Park Specialty Center
state: Kansas
city: Louisville
country: United States
facility: Norton Brownsboro Hospital
state: Kentucky
city: Baton Rouge
country: United States
facility: Optum Infusion - Baton Rouge
state: Louisiana
city: Lake Charles
country: United States
facility: Care Access - Lake Charles
state: Louisiana
city: Oxon Hill
country: United States
facility: MD Medical Research
state: Maryland
city: Methuen
country: United States
facility: ActivMed Practices and Research
state: Massachusetts
city: Newton
country: United States
facility: Boston Center for Memory
state: Massachusetts
city: Quincy
country: United States
facility: Care Access - Quincy
state: Massachusetts
city: Waltham
country: United States
facility: MedVadis Research Corporation
state: Massachusetts
city: Southfield
country: United States
facility: Revival Research Institute
state: Michigan
city: Burnsville
country: United States
facility: Minneapolis Clinic of Neurology - Burnsville Office
state: Minnesota
city: Mendota Heights
country: United States
facility: Coram CVS/Specialty Infusion Services - Mendota Heights
state: Minnesota
city: Fayette
country: United States
facility: SKY Clinical Research Network Group - Hall
state: Mississippi
city: Ridgeland
country: United States
facility: SKY Clinical Research Network Group-Quinn
state: Mississippi
city: Bolivar
country: United States
facility: Citizens Memorial Hospital District
state: Missouri
city: Chesterfield
country: United States
facility: Clinical Research Professionals
state: Missouri
city: Saint Louis
country: United States
facility: IMA Clinical Research - St. Louis
state: Missouri
city: Henderson
country: United States
facility: Coram CVS/Specialty Infusion Services - Henderson
state: Nevada
city: Las Vegas
country: United States
facility: Option Care - Las Vegas
state: Nevada
city: Las Vegas
country: United States
facility: Las Vegas Medical Research
state: Nevada
city: Hoboken
country: United States
facility: IMA Clinical Research Hoboken
state: New Jersey
city: Springfield
country: United States
facility: The Cognitive and Research Center of New Jersey
state: New Jersey
city: Warren
country: United States
facility: IMA Clinical Research Warren
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience Inc.
state: New Mexico
city: Albany
country: United States
facility: IMA Clinical Research Albany
state: New York
city: Albany
country: United States
facility: Neurological Associates Albany
state: New York
city: Bronx
country: United States
facility: Prime Global Research
state: New York
city: East Syracuse
country: United States
facility: Velocity Clinical Research, Syracuse
state: New York
city: Hartsdale
country: United States
facility: IMA Clinical Research Westchester
state: New York
city: New York
country: United States
facility: IMA Clinical Research
state: New York
city: Patchogue
country: United States
facility: South Shore Neurologic Associates
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Asheville
country: United States
facility: Asheville Neurology Specialists
state: North Carolina
city: Charlotte
country: United States
facility: Care Access - Charlotte
state: North Carolina
city: Fayetteville
country: United States
facility: Care Access - Fayetteville
state: North Carolina
city: Greensboro
country: United States
facility: Care Access - Greensboro
state: North Carolina
city: Greensboro
country: United States
facility: Medication Management
state: North Carolina
city: Kinston
country: United States
facility: Care Access - Kinston
state: North Carolina
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Morehead City
country: United States
facility: Carteret Medical Group
state: North Carolina
city: Raleigh
country: United States
facility: Care Access - Raleigh
state: North Carolina
city: Winston-Salem
country: United States
facility: Accellacare - Winston-Salem
state: North Carolina
city: Canton
country: United States
facility: NeuroScience Research Center
state: Ohio
city: Dayton
country: United States
facility: Hometown Urgent Care and Research - Cincinnati
state: Ohio
city: Dayton
country: United States
facility: Neurology Diagnostics, Inc.
state: Ohio
city: Lima
country: United States
facility: Care Access - Lima
state: Ohio
city: Middleburg Heights
country: United States
facility: North Star Medical Research
state: Ohio
city: Poland
country: United States
facility: Care Access - Youngstown
state: Ohio
city: Tulsa
country: United States
facility: Central States Research
state: Oklahoma
city: Bend
country: United States
facility: Optum Infusion - Bend
state: Oregon
city: Medford
country: United States
facility: Velocity Clinical Research, Medford
state: Oregon
city: Portland
country: United States
facility: Center for Cognitive Health
state: Oregon
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Pottsville
country: United States
facility: Care Access - Pottsville
state: Pennsylvania
city: Warwick
country: United States
facility: Care Access Research - Warwick
state: Rhode Island
city: Anderson
country: United States
facility: Care Access - Anderson
state: South Carolina
city: Anderson
country: United States
facility: Velocity Clinical Research, Anderson
state: South Carolina
city: Columbia
country: United States
facility: VitaLink Research - Columbia
state: South Carolina
city: Gaffney
country: United States
facility: Velocity Clinical Research, Gaffney
state: South Carolina
city: Greenville
country: United States
facility: VitaLink Research - Greenville
state: South Carolina
city: Mauldin
country: United States
facility: Care Access - Mauldin
state: South Carolina
city: Spartanburg
country: United States
facility: VitaLink Research - Spartanburg
state: South Carolina
city: Union
country: United States
facility: VitaLink Research - Union
state: South Carolina
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Cordova
country: United States
facility: Neurology Clinic
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
state: Tennessee
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology, P.A.
state: Texas
city: Austin
country: United States
facility: Senior Adults Specialty Research
state: Texas
city: Beaumont
country: United States
facility: Gadolin Research
state: Texas
city: Brownsville
country: United States
facility: Headlands Research - Brownsville
state: Texas
city: Conroe
country: United States
facility: Conroe Willis Medical Research
state: Texas
city: El Paso
country: United States
facility: Advanced Neuro Research Center - ANRC
state: Texas
city: Georgetown
country: United States
facility: Care Access - Georgetown
state: Texas
city: Houston
country: United States
facility: Optum Infusion - Houston
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
city: Houston
country: United States
facility: Next Level Urgent Care
state: Texas
city: McAllen
country: United States
facility: Family Practice Center
state: Texas
city: Rio Grande City
country: United States
facility: El Faro Health and Therapeutics
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research - Knickerbocker
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group
state: Texas
city: Shavano Park
country: United States
facility: Consano Clinical Research, LLC
state: Texas
city: Weslaco
country: United States
facility: Texas Valley Clinical Research
state: Texas
city: Bennington
country: United States
facility: The Memory Clinic
state: Vermont
city: Arlington
country: United States
facility: Care Access - Arlington
state: Virginia
city: Chantilly
country: United States
facility: Option Care - Chantilly
state: Virginia
city: Richmond
country: United States
facility: Dominion Medical Associates, Inc.
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Tacoma
country: United States
facility: Universal Research Group
state: Washington
city: Woodinville
country: United States
facility: Optum Infusion - Woodinville
state: Washington
city: Morgantown
country: United States
facility: Exemplar Research
state: West Virginia
city: Obu
country: Japan
facility: National Center for Geriatrics and Gerontology
state: Aichi
city: Yufu
country: Japan
facility: Oita University Hospital
state: Oita
city: Suita-shi
country: Japan
facility: Medical Corporation Heishinkai OCROM Clinic
state: Osaka
city: Bunkyo-ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
state: Tokyo
city: Chuo-ku
country: Japan
facility: Fukuwa Clinic
state: Tokyo
city: Hachioji
country: Japan
facility: P-One Clinic
state: Tokyo
city: Itabashi
country: Japan
facility: Tokyo Metropolitan Geriatric Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Heishinkai Medical Group ToCROM Clinic
state: Tokyo
city: Shinjuku
country: Japan
facility: Samoncho Clinic
state: Tokyo
city: Osaka
country: Japan
facility: AMC Nishiumeda Clinic
city: Tokyo
country: Japan
facility: Tokyo Asbo Clinic
city: Bayamon
country: Puerto Rico
facility: SCB Research Center
city: Caguas
country: Puerto Rico
facility: Dr. Samuel Sanchez PSC
city: San Juan
country: Puerto Rico
facility: INSPIRA Clinical Research
city: San Juan
country: Puerto Rico
facility: Instituto De Neurologia Dra. Ivonne Fraga
city: San Juan
country: Puerto Rico
facility: Mindful Medical Research
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico - Medical Sciences Campus_Do not use - Duplicate facility
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: