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Alzheimer DiseasePhase 2NCT03367403

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

A Phase 2 study testing Donanemab and LY3202626 in people with Alzheimer Disease, run by Eli Lilly and Company at 61 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 60 to 85 years
Conditions the study is for
Alzheimer Disease
What is being tested?
Donanemab and LY3202626
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
272 participants
Where
61 sitesin 2 countries
Study dates
18 Dec 2017to 21 Sep 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

61 sites in 2 countries.

61 sites in 2 countries

United States56 sites

  • JEM Research Institute

    Atlantis, Florida, 33462

  • Insight Clinical Trials

    Beachwood, Ohio, 44122

  • McLean Hospital

    Belmont, Massachusetts, 02478

  • The Memory Clinic

    Bennington, Vermont, 05201

  • Bradenton Research Center

    Bradenton, Florida, 34205

  • Behavioral Health Center Research

    Charlotte, North Carolina, 28211

  • Great Lakes Clinical Trials

    Chicago, Illinois, 60640

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • Texas Neurology, PA

    Dallas, Texas, 75214

  • Associated Neurologists, PC - Danbury

    Danbury, Connecticut, 06810

  • Neurology Diagnostics, Inc.

    Dayton, Ohio, 45459

  • Brain Matters Research

    Delray Beach, Florida, 33445

  • Alexian Brothers Medical Center

    Elk Grove Village, Illinois, 60007

  • Cognition Health

    Fairfax, Virginia, 22031

  • University of Kansas Hospital

    Fairway, Kansas, 66160

  • Neurology Center of North Orange County

    Fullerton, California, 92835

  • Guilford Neurologic Associates

    Greensboro, North Carolina, 27405

  • Infinity Clinical Research, LLC

    Hollywood, Florida, 33021

  • Houston Methodist

    Houston, Texas, 77030

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

  • Josephson Wallack Munshower Neurology

    Indianapolis, Indiana, 46256

  • Irvine Clinical Research Center

    Irvine, California, 92614

  • Institute for Memory Impairment & Neurological Disorders

    Irvine, California, 92697

  • Jacksonville Center for Clinical Research

    Jacksonville, Florida, 32216

  • Las Vegas Medical Research

    Las Vegas, Nevada, 89113

  • Merritt Island Medical Research LLC

    Merritt Island, Florida, 32592

  • ActivMed Practices & Research, Inc

    Methuen, Massachusetts, 01844

  • Pharmax Research Clinic

    Miami, Florida, 33126

  • Miami Jewish Health Systems

    Miami, Florida, 33137

  • Suncoast Clinical Research

    New Port Richey, Florida, 34652

  • Pharmacology Research Institute

    Newport Beach, California, 92660

  • Boston Center for Memory

    Newton, Massachusetts, 02459

  • Compass Research

    Orlando, Florida, 32806

  • Palm Beach Neurological Group

    Palm Beach Gardens, Florida, 33410

  • Banner Alzheimer's Institute

    Phoenix, Arizona, 85006

  • Donald S Marks

    Plymouth, Massachusetts, 02360-4843

  • Quantum Laboratories

    Pompano Beach, Florida, 33064

  • Progressive Medical Research

    Port Orange, Florida, 32127

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Butler Hospital

    Providence, Rhode Island, 02906

  • Raleigh Neurology Associates

    Raleigh, North Carolina, 27607

  • National Clinical Research - Richmond

    Richmond, Virginia, 23294

  • Pacific Research Network Inc

    San Diego, California, 92103

  • Sharp Mesa Vista Hospital

    San Diego, California, 92123

  • Syrentis Clinical Research

    Santa Ana, California, 92705

  • Intercoastal Medical Group

    Sarasota, Florida, 34239

  • Washington University

    St Louis, Missouri, 63108

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

    Stamford, Connecticut, 06905

  • Banner Sun Health Research Institute

    Sun City, Arizona, 85351

  • Axiom Research

    Tampa, Florida, 33609

  • Stedman Clinical Trials

    Tampa, Florida, 33613

  • Compass Research

    The Villages, Florida, 32162

  • Advanced Memory Research Institute of New Jersey

    Toms River, New Jersey, 08755

  • Cotton O'Neil Clinic

    Topeka, Kansas, 66606

  • Abington Neurological Associates

    Willow Grove, Pennsylvania, 19090

  • Piedmont Medical Research

    Winston-Salem, North Carolina, 27103

Other trials in United States

Canada5 sites

  • Clinique de la Memoire de l'Outaouais

    Gatineau, Quebec, J8T 8J1

  • Bruyere Research Institute

    Ottawa, Ontario, K1N 5C8

  • Kawartha Regional Memory Clinic

    Peterborough, Ontario, K9H2P4

  • DIEX Recherche Sherbrooke, Inc

    Sherbrooke, Quebec, J1L 0H8

  • Toronto Memory Program

    Toronto, Ontario, M3B2S7

Other trials in Canada

About this study

Official title: Assessment of Safety, Tolerability and Efficacy of LY3002813 in Early Symptomatic Alzheimer's Disease

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

Being tested
Donanemab, Placebo, LY3202626
Keywords
TRAILBLAZER-ALZ
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DonanemabDrug

    Also called LY3002813

    Administered IV

  • PlaceboDrug

    Administered IV

  • LY3202626Drug

    Administered orally

Study groups in NCT03367403
Study groupRoleWhat they receive
Donanemab Monotherapy (Donanemab-M)ExperimentalParticipants 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.
Receives: Drug: Donanemab
PlaceboPlacebo comparatorParticipants received placebo IV Q4W for up to 72 weeks.
Receives: Drug: Placebo
Donanemab in Combination With LY3202626 (Donanemab-C)ExperimentalParticipants 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.
Receives: Drug: Donanemab; Drug: LY3202626

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, 76 Weeks

Secondary outcomes (7)

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

    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 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 controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    Measured: Baseline, 76 Weeks

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

    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 controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    Measured: Baseline, 76 Weeks

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

    MMSE is a brief screening 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 controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    Measured: Baseline, 76 Weeks

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

    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 controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    Measured: Baseline, 76 Weeks

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

    Florbetapir PET imaging was used as a quantitative amyloid biomarker. Florbetapir 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 areas of the brain 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. Least Squares mean change was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.

    Measured: Baseline, 76 Weeks

  6. Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan

    Flortaucipir PET imaging was used as a quantitative tau biomarker. Flortaucipir 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 two measures: weighted average Standardized Uptake Value Ratio (MUBADA SUVR) in the brain relative to the cerebellum gray as a reference region and the global tau load (TauL) generated using a TauIQ method. Larger weighted average SUVR reflects the larger cortical tau burden relative to cerebellum gray. The TauIQ method quantifies the spatiotemporal accumulation pattern of tau and larger TauL value reflects the larger global tau level in the brain as determined using a TauIQ mathematical framework. Least Squares mean change was controlled for baseline + age + treatment (Type III sum of squares).

    Measured: Baseline, 76 Weeks

  7. 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 atrophy. Volumetric MRI (vMRI) parameters were measured in 14 brain regions: bilateral cortical, bilateral entorhinal cortex, bilateral hippocampus, bilateral inferior parietal lobe, bilateral isthmus cingulate, bilateral lateral parietal lobe, bilateral medial temporal lobe, bilateral precuneus, bilateral prefrontal lobe, bilateral superior temporal lobe, bilateral ventricles, bilateral whole brain, bilateral whole temporal lobe, and bilateral white matter. The atrophy was assessed by tensor-based morphometry, which captures volume changes within the deformation map. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, fixed covariates of baseline, and age at baseline.

    Measured: Baseline, 76 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2017
  2. Study start18 Dec 2017
  3. Primary completion4 Dec 2020
  4. Study completion21 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
272 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03367403
Sponsor's protocol ID
16933
Other IDs
I5T-MC-AACG
Status last verified
Sep 2022
First submitted
5 Dec 2017
Last updated
19 Mar 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Brookfield N, Hauck PM, Doty EG, Zimmer JA, Yang F, Chen YF, Ardayfio P, Khanna R, Ye W, Tockhorn-Heidenreich A, Patel N. Donanemab for early symptomatic AD in the UK-indicated population: safety and efficacy in those who are non-carriers or heterozygous for APOE epsilon4. Neurodegener Dis Manag. 2026 Aug 26:1-11. doi: 10.1080/17582024.2026.2723524. Online ahead of print.

    PubMed 42644303

  • 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.

    PubMed 41804324

  • Gueorguieva I, Chow K, Chua L, Shcherbinin S, Zimmer JA, Evans CD, Wang H, Nery ESM, Brooks DA, Sims JR. Donanemab exposure-response in early symptomatic Alzheimer's disease. Alzheimers Dement. 2025 Jul;21(7):e70491. doi: 10.1002/alz.70491.

    PubMed 40667684

  • 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.

    PubMed 40603145

  • 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.

    PubMed 40063015

  • 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.

    PubMed 38323738

  • 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.

    PubMed 36251300

  • 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.

    PubMed 36094645

  • 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.

    PubMed 33720637

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Donanemab and LY3202626 in people with Alzheimer Disease, run by Eli Lilly and Company at 61 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS) Score (time frame: Baseline, 76 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03367403, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2026.

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