A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)

Alzheimer Disease Clinical Trial

Official title:

Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04437511
• Other study ID #: 17737
• Secondary ID: I5T-MC-AACI2020-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 19, 2020
• Est. completion date: August 22, 2025

Study information

• Verified date: May 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer's disease.

Additional participants will be enrolled to an addendum safety cohort. The participants will be administered open-label donanemab.

Description:

TRAILBLAZER-ALZ 2 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of N3pG antibody (donanemab) in participants with early symptomatic AD (prodromal AD and mild dementia due to AD) with the presence of brain amyloid and tau pathology.

Following the double-blind 76-week main study period, a double-blind 78-week long-term extension period is added to further evaluate donanemab efficacy and safety over time. Participants from the addendum safety cohort are not eligible for the extension period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1736
• Est. completion date: August 22, 2025
• Est. primary completion date: April 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

Inclusion Criteria:

• Gradual and progressive change in memory function reported by participants or informants for = 6 months

• MMSE score of 20 to 28 (inclusive) at baseline

• Meet 18F flortaucipir PET scan (central read) criteria - does not apply to safety cohort

• Meet 18F florbetapir PET scan (central read) criteria

• Have a study partner who will provide written informed consent to participate

Exclusion Criteria:

• Contraindication to MRI or PET scans

• Current treatment with immunoglobulin G (IgG) therapy

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Donanemab
Given IV
• Placebo
Given IV

Locations

Country	Name	City	State
Australia	NeuroCentrix	Carlton	Victoria
Australia	Central Coast Neurosciences Research	Erina	New South Wales
Australia	Delmont Private Hospital	Glen Iris	Victoria
Australia	HammondCare	Malvern	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	The Royal Melbourne Hospital	Parkville	Victoria
Australia	HammondCare Greenwich Hospital	Sydney	New South Wales
Australia	KARA Institute for Neurological Diseases	Sydney	New South Wales
Australia	St Vincent's Hospital	Sydney	New South Wales
Canada	Clinique de la Mémoire de l'Outaouais	Gatineau	Quebec
Canada	MoCA Research and Innovation Inc.	Greenfield Park	Quebec
Canada	True North Clinical Research	Halifax	Nova Scotia
Canada	OCT Research ULC	Kelowna	British Columbia
Canada	True North Clinical Research	New Minas	Nova Scotia
Canada	SKDS Research Inc.	Newmarket	Ontario
Canada	Bruyère Research Institute	Ottawa	Ontario
Canada	Ottawa Memory Clinic	Ottawa	Ontario
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	Alpha Recherche Clinique	Quebec
Canada	ALPHA Recherche Clinique	Quebec
Canada	Bluewater Clinical Research Group Inc.	Sarnia	Ontario
Canada	Diex Recherche Sherbrooke Inc.	Sherbrooke	Quebec
Canada	Q&T Research Sherbrooke Inc.	Sherbrooke	Quebec
Canada	Baycrest Health Sciences	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto Memory Program	Toronto	Ontario
Czechia	Clinline Services	Hostivice	Stredoceský Kraj
Czechia	Brain-Soul Therapy	Kladno	Stredoceský Kraj
Czechia	A-Shine	Pilsen	Plzen-mesto
Czechia	Neuropsychiatrie	Prague	Praha 6
Czechia	Clintrial s.r.o.	Praha	Praha 10
Czechia	Neurologická Ambulance - Forbeli	Praha	Praha 6
Japan	Matsui e-clinic	Akashi	Hyogo
Japan	Medical Corporation Chiseikai Tokyo Center Clinic	Chuo-ku	Tokyo
Japan	Moriyama Neuro Center Hospital	Edogawa-ku	Tokyo
Japan	P-One Clinic	Hachioji	Tokyo
Japan	Himeji Central Hospital Affiliated Clinic	Himeji	Hyogo
Japan	Hiroshima Neurology Clinic	Hiroshima
Japan	Honmachi Clinic	Ikeda	Osaka
Japan	Inage Neurology and Memory Clinic	Inage	Chiba
Japan	Tokyo Medical University Ibaraki Medical Center	Inashiki	Ibaraki
Japan	Kakigi Dementia Happiness Clinic	Kobe	Hyogo
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Kobe University Hospital	Kobe	Hyogo
Japan	Katayama Medical Clinic	Kurashiki	Okayama
Japan	Ishikawa Clinic	Kyoto
Japan	Koseikai Takeda Hospital	Kyoto
Japan	National hospital Organization Utano National Hospital	Kyoto
Japan	Chubu Rosai Hospital	Nagoya	Aichi
Japan	Kojunkai Daido Clinic	Nagoya	Aichi
Japan	Nagoya Ekisaikai Hospital	Nagoya-shi	Aichi
Japan	National Center for Geriatrics and Gerontology	Obu	Aichi
Japan	Oita Prefectural Hospital	Oita
Japan	Clinical Research Hospital Tokyo	Shinjuku-ku	Tokyo
Japan	Tokyo Metro Bokutoh Hospital	Sumida-ku	Tokyo
Japan	Takatsuki General Hospital	Takatsuki	Osaka
Japan	Itsuki Hospital	Tokushima
Japan	Makita General Hospital	Tokyo
Japan	Nippon Medical School Hospital	Tokyo
Japan	Tokyo Asbo Clinic	Tokyo
Japan	Memory Clinic Toride	Toride	Ibaraki
Japan	Yokohama City Minato Red Cross Hospital	Yokohama	Kanagawa
Japan	Oita University Hospital	Yufu	Oita
Netherlands	Brain Research Center Den Bosch B.V.	's-Hertogenbosch	Noord-Brabant
Netherlands	Brain Research Center	Amsterdam	Noord-Holland
Netherlands	QPS Netherlands B.V	Leeuwarden	Fryslân
Netherlands	Brain Research Center Zwolle	Zwolle	Overijssel
Poland	KLIMED Marek Klimkiewicz	Bialystok	Podlaskie
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok	Podlaskie
Poland	Centrum Medyczne NEUROMED	Bydgoszcz	Kujawsko-pomorskie
Poland	Centrum Badan Klinicznych PI-House sp. z o.o.	Gdansk	Pomorskie
Poland	Klinika Neuro-Care	Katowice	Slaskie
Poland	Diamond Clinic	Krakow	Malopolskie
Poland	Private Practice - Dr. Urszula Chyrchel- Paszkiewicz	Lublin	Lubelskie
Poland	Nzoz Neuro-Kard Ilkowski i Partnerzy SPL	Poznan	Wielkopolskie
Poland	Osrodek Badawczo Naukowo Dydaktyczny Chorób Otepiennych Im Ksiedza Henryka Kardynala Gulbinowicza Uniwersy -T	Scinawa	Dolnoslaskie
Poland	Centrum Medyczne SENIOR	Sopot	Pomorskie
Poland	Centrum Medyczne Euromedis	Szczecin	Zachodniopomorskie
Poland	Centrum Medyczne NeuroProtect	Warsawawa	Mazowieckie
Poland	Centrum Medyczne AMED	Warszawa	Mazowieckie
Poland	Wroclawskie Centrum Alzheimerowskie	Wroclaw	Dolnoslaskie
Puerto Rico	SCB Research Center	Bayamon
Puerto Rico	Barbara Diaz-Hernandez MD Research, Inc.	San Juan
Puerto Rico	INSPIRA Clinical Research	San Juan
Puerto Rico	Instituto De Neurologia Dra. Ivonne Fraga	San Juan
United Kingdom	Re:Cognition Health - Birmingham	Birmingham
United Kingdom	Re:Cognition Health Guildford	Guildford	Surrey
United Kingdom	Re:Cognition Health - London	London	London, City Of
United Kingdom	Glasgow Memory Clinic	Motherwell	Great Britain
United States	Abington Neurological Associates, Ltd.	Abington	Pennsylvania
United States	Albany Medical College	Albany	New York
United States	Neurological Associates Albany	Albany	New York
United States	McFarland Clinic, PC	Ames	Iowa
United States	Dent Neurologic Institute	Amherst	New York
United States	Integrated Neurology Services - Falls Church	Arlington	Virginia
United States	JEM Research Institute	Atlantis	Florida
United States	Senior Adults Specialty Research	Austin	Texas
United States	VIN-Julie Schwartzbard	Aventura	Florida
United States	Mountain Neurological Research Center	Basalt	Colorado
United States	Gadolin Research	Beaumont	Texas
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	The Memory Clinic	Bennington	Vermont
United States	Neurology Offices of South Florida	Boca Raton	Florida
United States	SFM Clinical Research	Boca Raton	Florida
United States	Northwest Clinical Trials	Boise	Idaho
United States	Boston Clinical Trials	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Alpine Clinical Research Center	Boulder	Colorado
United States	University at Buffalo - UBMD Neurology	Buffalo	New York
United States	Gwinnett Research Institute	Buford	Georgia
United States	NeuroScience Research Center	Canton	Ohio
United States	North County Neurology Associates	Carlsbad	California
United States	Valley Medical Research	Centerville	Ohio
United States	CHS-Behavioral Health Research	Charlotte	North Carolina
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Great Lakes Clinical Trials - Andersonville	Chicago	Illinois
United States	Rapid Medical Research	Cleveland	Ohio
United States	Colorado Springs Neurological Associates	Colorado Springs	Colorado
United States	Prism Health Richland Department of Neurology Research	Columbia	South Carolina
United States	Columbus Memory Center, LLC	Columbus	Georgia
United States	Ohio State University	Columbus	Ohio
United States	Neurology Clinic, P.C.	Cordova	Tennessee
United States	Kerwin Medical Center	Dallas	Texas
United States	Neurology Consultants of Dallas, PA	Dallas	Texas
United States	Neurology Diagnostics, Inc.	Dayton	Ohio
United States	University of Cincinnati Physicians Company, LLC	Dayton	Ohio
United States	ARS-Neurostudies	Decatur	Georgia
United States	Brain Matters Research	Delray Beach	Florida
United States	Cohen Medical Associates	Delray Beach	Florida
United States	Colorado Neurological Research Center, PC	Denver	Colorado
United States	InSite Clinical Research	DeSoto	Texas
United States	Integrity Clinical Research	Doral	Florida
United States	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island
United States	Clarity Clinical Research	East Syracuse	New York
United States	AMITA Health - Alexian Brothers Neurosciences Institute Clinical Research	Elk Grove Village	Illinois
United States	Wr- Pri, Llc	Encino	California
United States	The University of Kansas - Clinical Research Center	Fairway	Kansas
United States	NECCR PrimaCare Research	Fall River	Massachusetts
United States	QUEST Research Institute	Farmington Hills	Michigan
United States	Health Initiatives Research	Fayetteville	Arkansas
United States	Precise Research Centers	Flowood	Mississippi
United States	Neuropsychiatric Research Center of Southwest Florida	Fort Myers	Florida
United States	Neuro-Pain Medical Center	Fresno	California
United States	Neurology Center of North Orange County	Fullerton	California
United States	Center for Advanced Research & Education	Gainesville	Georgia
United States	Gilbert Neurology	Gilbert	Arizona
United States	Finlay Medical Research	Greenacres City	Florida
United States	Guilford Neurologic Associates, Inc	Greensboro	North Carolina
United States	MD Clinical	Hallandale Beach	Florida
United States	AGA Clinical Trials	Hialeah	Florida
United States	Indago Research & Health Center, Inc	Hialeah	Florida
United States	Infinity Clinical Research, LLC	Hollywood	Florida
United States	Houston Methodist Hospital	Houston	Texas
United States	The University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Josephson Wallack Munshower Neurology, PC	Indianapolis	Indiana
United States	Irvine Clinical Research	Irvine	California
United States	Encore Research Group- Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	EvergreenHealth Medical Center	Kirkland	Washington
United States	Kaizen Brain Center	La Jolla	California
United States	Senior Clinical Trials, Inc.	Laguna Hills	California
United States	Accel Research Sites - Lakeland Clinical Research Unit	Lakeland	Florida
United States	Las Vegas Medical Research	Las Vegas	Nevada
United States	Collaborative Neuroscience Research, LLC	Los Alamitos	California
United States	Clinical Research Institute	Los Angeles	California
United States	USC Keck School of Medicine	Los Angeles	California
United States	ClinCloud - Maitland	Maitland	Florida
United States	AMC Research	Matthews	North Carolina
United States	Clinical Neuroscience Solutions, Inc. dba CNS Healthcare	Memphis	Tennessee
United States	Merritt Island Medical Research, LLC	Merritt Island	Florida
United States	Allied Biomedical Research Institute	Miami	Florida
United States	Ezy Medical Research	Miami	Florida
United States	Finlay Medical Research	Miami	Florida
United States	Florida International Research Center	Miami	Florida
United States	Future Care Solution	Miami	Florida
United States	Homestead Associates in Research	Miami	Florida
United States	Miami Dade Medical Research Institute, LLC	Miami	Florida
United States	Miami Jewish health	Miami	Florida
United States	New Horizon Research Center	Miami	Florida
United States	Optimus U Corporation	Miami	Florida
United States	The Neurology Research Group	Miami	Florida
United States	VIN-Victor Faradji	Miami	Florida
United States	Mount Sinai Cancer Center	Miami Beach	Florida
United States	Goji Group - Research Trials Group	Miami Lakes	Florida
United States	Carteret Medical Group	Morehead City	North Carolina
United States	Neurovations	Napa	California
United States	Collier Neurologic Specialists	Naples	Florida
United States	BTC Network	New Bedford	Massachusetts
United States	Institute for Neurodegenerative Disorders	New Haven	Connecticut
United States	Yale University, Alzheimer's Disease Research Unit	New Haven	Connecticut
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	NYU Langone Health	New York	New York
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Boston Center for Memory	Newton	Massachusetts
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	North Kansas City Hospital	North Kansas City	Missouri
United States	Research Center for Clinical Studies	Norwalk	Connecticut
United States	Renstar Medical Research	Ocala	Florida
United States	Sensible Healthcare, LLC	Ocoee	Florida
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	Headlands Research Orlando	Orlando	Florida
United States	Synexus Clinical Research US, Inc.	Orlando	Florida
United States	College Park Family Care Center/Multi Specialty Clinical Res	Overland Park	Kansas
United States	Sharlin Health and Neurology	Ozark	Missouri
United States	IMIC, Inc.	Palmetto Bay	Florida
United States	Stanford Neuroscience Health Center	Palo Alto	California
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	SC3 Research - Pasadena	Pasadena	California
United States	Emerald Coast Neurology - Airport Boulevard	Pensacola	Florida
United States	Penn Medicine: University of Pennsylvania Health System	Philadelphia	Pennsylvania
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Xenoscience	Phoenix	Arizona
United States	Donald S. Marks M.D., P.C.	Plymouth	Massachusetts
United States	Keystone Clinical Studies	Plymouth Meeting	Pennsylvania
United States	Quantum Laboratories Clinical Research	Pompano Beach	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	EPIC Imaging	Portland	Oregon
United States	Summit Headlands	Portland	Oregon
United States	PCND Neurology	Poway	California
United States	Alzheimers Disease Center	Quincy	Massachusetts
United States	Anderson Clinical Research	Redlands	California
United States	National Clinical Research, Inc	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Central Texas Neurology Consultants	Round Rock	Texas
United States	Arch Clinical Trials	Saint Louis	Missouri
United States	Suncoast Neuroscience Associates, Inc.	Saint Petersburg	Florida
United States	Glenn Biggs Institute for Alzheimers & Neurodegenerative Diseases	San Antonio	Texas
United States	Artemis Institute for Clinical Research	San Diego	California
United States	Pacific Research Network	San Diego	California
United States	Sharp Neurocognitive Research Center	San Diego	California
United States	UCSF Memory and Aging Center	San Francisco	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	Intercoastal Medical Group	Sarasota	Florida
United States	Roskamp Institute Clinical Trials Division	Sarasota	Florida
United States	Maine Medical Center-Maine Medical Partners Neurology	Scarborough	Maine
United States	Perseverance Research Center	Scottsdale	Arizona
United States	University of Washington - Harborview Medical Center	Seattle	Washington
United States	California Neuroscience Research Medical Group, Inc.	Sherman Oaks	California
United States	Kingfisher Cooperative	Spokane	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	The Cognitive and Research Center of New Jersey	Springfield	New Jersey
United States	Ki Health Partners, LLc, dba New England Institute for Clinical Research	Stamford	Connecticut
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Alzheimer's Research and Treatment Center	Stuart	Florida
United States	Brain Matters Research	Stuart	Florida
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Universal Research Group	Tacoma	Washington
United States	Tallahassee Neurological Clinic	Tallahassee	Florida
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Stedman Clinical Trials	Tampa	Florida
United States	USF Health Byrd Alzheimer's Institute	Tampa	Florida
United States	Charter Research - Lady Lake	The Villages	Florida
United States	Synexus Clinical Research US, Inc.	The Villages	Florida
United States	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey
United States	Bio Behavioral Health	Toms River	New Jersey
United States	Cotton O'Neil Clinical Research Center - Central Office	Topeka	Kansas
United States	Banner Alzheimer's Institute Tucson	Tucson	Arizona
United States	Center for Neurosciences	Tucson	Arizona
United States	Central States Research	Tulsa	Oklahoma
United States	Tilda Research	Tustin	California
United States	MedVadis Research Corporation	Waltham	Massachusetts
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Covenant Medical Center	Waterloo	Iowa
United States	Adams Clinical	Watertown	Massachusetts
United States	Alzheimer's Research and Treatment Center	Wellington	Florida
United States	Palm Beach Neurology	West Palm Beach	Florida
United States	Ascension Via Christi Research	Wichita	Kansas
United States	Accellacare - Winston-Salem	Winston-Salem	North Carolina
United States	Charter Research - Winter Park	Winter Park	Florida
United States	Conquest Research	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Japan,  Netherlands,  Poland,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Overall Population)	Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the ADAS-Cog13 and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. Least Squares (LS) Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline acetylcholinesterase inhibitor (AchI)/Memantine use.	Baseline, Week 76
Primary	Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)	Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline on the Mini Mental State Examination (MMSE) Score (Overall Population)	MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline on the Mini Mental State Examination (MMSE) Score (Intermediate (Low-medium) Tau Population)	MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population)	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. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)	The ADAS 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-cog 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. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Overall Population)	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. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, age at baseline, baseline tau category, pooled investigator, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)	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. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, age at baseline, pooled investigator, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score (Overall Population)	The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score (Intermediate (Low-medium) Tau Population)	The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.	Baseline, Week 76
Secondary	Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan	Amyloid PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in amyloid plaques. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical brain regions relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, baseline tau category, and age at baseline.	Baseline, Week 76
Secondary	Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan	Flortaucipir PET imaging was used as a quantitative tau biomarker. Tau PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in aggregated tau neurofibrillary tangles (NFTs). Quantitative tau burden was formalized using Standardized Uptake Value Ratio (SUVR) in frontal lobe relative to the cerebellum gray as a reference region. Larger SUVR reflects larger tau burden in the frontal lobe relative to cerebellum gray. LS Mean value was adjusted for baseline score, screening tau category, age and treatment (Type III sum of squares).	Baseline, Week 76
Secondary	Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)	MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain volume. Volumetric MRI parameters were measured in bilateral hippocampus, bilateral whole brain, and bilateral ventricles. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline tau category, and age at baseline.	Baseline, Week 76
Secondary	Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab	The average serum concentration at steady state, calculated as Cav = AUCtau/tau, where tau is the dosing interval (4 weeks). AUCtau/tau was assessed at week 12, 16, 24, 36, 52, 64 and Cav for the dosing interval from week 16 to week 20 is reported.	Week 16 to week 20
Secondary	Number or Participants With Anti-Donanemab Antibodies	Number of participants with treatment-emergent positive Anti-Donanemab antibodies was summarized by treatment group.	Baseline through Week 76

External Links

•   A Study of Donanemab (LY3002813) in Participants with Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)