NCT03367403

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and efficacy of LY3002813 in early symptomatic Alzheimer's disease.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
272

participants targeted

Target at P75+ for phase_2 alzheimer-disease

Timeline
Completed

Started Dec 2017

Typical duration for phase_2 alzheimer-disease

Geographic Reach
2 countries

61 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 5, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 8, 2017

Completed
10 days until next milestone

Study Start

First participant enrolled

December 18, 2017

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 4, 2020

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 21, 2021

Completed
5 months until next milestone

Results Posted

Study results publicly available

February 15, 2022

Completed
Last Updated

March 19, 2026

Status Verified

September 1, 2022

Enrollment Period

3 years

First QC Date

December 5, 2017

Results QC Date

December 1, 2021

Last Update Submit

March 5, 2026

Conditions

Keywords

TRAILBLAZER-ALZ

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS) Score

    Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the cognitive and functional decline associated with AD compared with placebo. iADRS is a simple linear combination of 13-item 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. Least Squares (LS) Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, acetylcholinesterase inhibitor (AChEI) and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    Baseline, 76 Weeks

Secondary Outcomes (7)

  • Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score

    Baseline, 76 Weeks

  • Change From Baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score

    Baseline, 76 Weeks

  • Change From Baseline in the Mini Mental State Examination (MMSE) Score

    Baseline, 76 Weeks

  • Change From Baseline in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-iADL) Score

    Baseline, 76 Weeks

  • Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan

    Baseline, 76 Weeks

  • +2 more secondary outcomes

Study Arms (3)

Donanemab Monotherapy (Donanemab-M)

EXPERIMENTAL

Participants received 700 milligram (mg) donanemab intravenously (IV) every 4 weeks (Q4W) x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks.

Drug: Donanemab

Placebo

PLACEBO COMPARATOR

Participants received placebo IV Q4W for up to 72 weeks.

Drug: Placebo

Donanemab in Combination With LY3202626 (Donanemab-C)

EXPERIMENTAL

Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W in combination with 12 mg of LY3202626 orally for up to 72 weeks. As per protocol amendment (d) approved on Oct 9, 2018, donanemab in combination with LY3202626 (donanemab-C) arm discontinued as there was a low probability of identifying a statistically significant effect of 12mg of LY3202626 slowing cognitive decline.

Drug: DonanemabDrug: LY3202626

Interventions

Administered orally

Donanemab in Combination With LY3202626 (Donanemab-C)

Administered IV

Also known as: LY3002813
Donanemab Monotherapy (Donanemab-M)Donanemab in Combination With LY3202626 (Donanemab-C)

Administered IV

Placebo

Eligibility Criteria

Age60 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months.
  • MMSE score of 20 to 28 (inclusive) at baseline or an acceptable historical flortaucipir PET scan within 6 months prior to baseline that meets the central read criteria.
  • Meet 18F flortaucipir PET scan eligibility criteria.
  • Meet 18F florbetapir PET scan (central read) eligibility criteria.

You may not qualify if:

  • Have a history of long QT syndrome.
  • Have received treatment with a stable dose of an acetylcholinesterase inhibitor (AChEI) and/or memantine for less than 2 months before randomization.
  • Contraindication to MRI.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (61)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Neurology Center of North Orange County

Fullerton, California, 92835, United States

Location

Irvine Clinical Research Center

Irvine, California, 92614, United States

Location

Institute for Memory Impairment & Neurological Disorders

Irvine, California, 92697, United States

Location

Pharmacology Research Institute

Newport Beach, California, 92660, United States

Location

Pacific Research Network Inc

San Diego, California, 92103, United States

Location

Sharp Mesa Vista Hospital

San Diego, California, 92123, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Associated Neurologists, PC - Danbury

Danbury, Connecticut, 06810, United States

Location

KI Health Partners, LLC d/b/a NE Inst. for Clin. Res.

Stamford, Connecticut, 06905, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Bradenton Research Center

Bradenton, Florida, 34205, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Infinity Clinical Research, LLC

Hollywood, Florida, 33021, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Merritt Island Medical Research LLC

Merritt Island, Florida, 32592, United States

Location

Pharmax Research Clinic

Miami, Florida, 33126, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Suncoast Clinical Research

New Port Richey, Florida, 34652, United States

Location

Compass Research

Orlando, Florida, 32806, United States

Location

Palm Beach Neurological Group

Palm Beach Gardens, Florida, 33410, United States

Location

Quantum Laboratories

Pompano Beach, Florida, 33064, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Intercoastal Medical Group

Sarasota, Florida, 34239, United States

Location

Axiom Research

Tampa, Florida, 33609, United States

Location

Stedman Clinical Trials

Tampa, Florida, 33613, United States

Location

Compass Research

The Villages, Florida, 32162, United States

Location

Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

Alexian Brothers Medical Center

Elk Grove Village, Illinois, 60007, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Josephson Wallack Munshower Neurology

Indianapolis, Indiana, 46256, United States

Location

University of Kansas Hospital

Fairway, Kansas, 66160, United States

Location

Cotton O'Neil Clinic

Topeka, Kansas, 66606, United States

Location

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

ActivMed Practices & Research, Inc

Methuen, Massachusetts, 01844, United States

Location

Boston Center for Memory

Newton, Massachusetts, 02459, United States

Location

Donald S Marks

Plymouth, Massachusetts, 02360-4843, United States

Location

Washington University

St Louis, Missouri, 63108, United States

Location

Las Vegas Medical Research

Las Vegas, Nevada, 89113, United States

Location

Advanced Memory Research Institute of New Jersey

Toms River, New Jersey, 08755, United States

Location

Behavioral Health Center Research

Charlotte, North Carolina, 28211, United States

Location

Guilford Neurologic Associates

Greensboro, North Carolina, 27405, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607, United States

Location

Piedmont Medical Research

Winston-Salem, North Carolina, 27103, United States

Location

Insight Clinical Trials

Beachwood, Ohio, 44122, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Neurology Diagnostics, Inc.

Dayton, Ohio, 45459, United States

Location

Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Texas Neurology, PA

Dallas, Texas, 75214, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

The Memory Clinic

Bennington, Vermont, 05201, United States

Location

Cognition Health

Fairfax, Virginia, 22031, United States

Location

National Clinical Research - Richmond

Richmond, Virginia, 23294, United States

Location

Bruyere Research Institute

Ottawa, Ontario, K1N 5C8, Canada

Location

Kawartha Regional Memory Clinic

Peterborough, Ontario, K9H2P4, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B2S7, Canada

Location

Clinique de la Memoire de l'Outaouais

Gatineau, Quebec, J8T 8J1, Canada

Location

DIEX Recherche Sherbrooke, Inc

Sherbrooke, Quebec, J1L 0H8, Canada

Location

Related Publications (7)

  • Ardayfio P, Mullins GR, Khanna R, Zimmer JA, Wang H, Nery ESM, Evans CD, Piela P, Battioui C, Lauzon S, Anglin G, Ng HW, Jayaraman AR, Agada N, Natalie CR, Brooks DA, Sims JR. Infusion-related reactions in donanemab-treated participants with early symptomatic Alzheimer's disease. Alzheimers Dement (N Y). 2026 Mar 8;12(1):e70229. doi: 10.1002/trc2.70229. eCollection 2026 Jan-Mar.

  • Chandler JM, Lansdall CJ, Ye W, McDougall F, Belger M, Toth B, Mi X, Sink KM, Atkins AS. The Alzheimer's Disease Cooperative Study - Activities of Daily Living dependence score: revision and validation of an algorithm evaluating patient dependence across the spectrum of AD severity. J Prev Alzheimers Dis. 2025 Sep;12(8):100261. doi: 10.1016/j.tjpad.2025.100261. Epub 2025 Jul 1.

  • Zimmer JA, Ardayfio P, Wang H, Khanna R, Evans CD, Lu M, Sparks J, Andersen S, Lauzon S, Nery ESM, Battioui C, Engle SE, Biffi A, Svaldi D, Salloway S, Greenberg SM, Sperling RA, Mintun M, Brooks DA, Sims JR. Amyloid-Related Imaging Abnormalities With Donanemab in Early Symptomatic Alzheimer Disease: Secondary Analysis of the TRAILBLAZER-ALZ and ALZ 2 Randomized Clinical Trials. JAMA Neurol. 2025 May 1;82(5):461-469. doi: 10.1001/jamaneurol.2025.0065.

  • Klein EG, Schroeder K, Wessels AM, Phipps A, Japha M, Schilling T, Zimmer JA. How donanemab data address the coverage with evidence development questions. Alzheimers Dement. 2024 Apr;20(4):3127-3140. doi: 10.1002/alz.13700. Epub 2024 Feb 7.

  • Pontecorvo MJ, Lu M, Burnham SC, Schade AE, Dage JL, Shcherbinin S, Collins EC, Sims JR, Mintun MA. Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ Randomized Clinical Trial. JAMA Neurol. 2022 Dec 1;79(12):1250-1259. doi: 10.1001/jamaneurol.2022.3392.

  • Shcherbinin S, Evans CD, Lu M, Andersen SW, Pontecorvo MJ, Willis BA, Gueorguieva I, Hauck PM, Brooks DA, Mintun MA, Sims JR. Association of Amyloid Reduction After Donanemab Treatment With Tau Pathology and Clinical Outcomes: The TRAILBLAZER-ALZ Randomized Clinical Trial. JAMA Neurol. 2022 Oct 1;79(10):1015-1024. doi: 10.1001/jamaneurol.2022.2793.

  • Mintun MA, Lo AC, Duggan Evans C, Wessels AM, Ardayfio PA, Andersen SW, Shcherbinin S, Sparks J, Sims JR, Brys M, Apostolova LG, Salloway SP, Skovronsky DM. Donanemab in Early Alzheimer's Disease. N Engl J Med. 2021 May 6;384(18):1691-1704. doi: 10.1056/NEJMoa2100708. Epub 2021 Mar 13.

Related Links

MeSH Terms

Conditions

Alzheimer Disease

Interventions

donanemabLY3202626

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Limitations and Caveats

As per protocol amendment (d) approved on Oct 9, 2018, donanemab in combination with LY3202626 (donanemab-C) arm discontinued as there was a low probability of identifying a statistically significant effect of 12mg of LY3202626 slowing cognitive decline. Clinical efficacy was not reported for this group.

Results Point of Contact

Title
Chief Medical Officer
Organization
Eli Lilly and Company

Study Officials

  • 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)

    Eli Lilly and Company

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 5, 2017

First Posted

December 8, 2017

Study Start

December 18, 2017

Primary Completion

December 4, 2020

Study Completion

September 21, 2021

Last Updated

March 19, 2026

Results First Posted

February 15, 2022

Record last verified: 2022-09

Data Sharing

IPD Sharing
Will share

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria
A research proposal should be approved by an independent review panel and researchers should sign a data sharing agreement.
More information

Locations