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Alzheimer DiseasePhase 2NCT04640077

A Follow-On Study of Donanemab (LY3002813) With Video Assessments in Participants With Alzheimer's Disease (TRAILBLAZER-EXT)

A Phase 2 study testing donanemab in people with Alzheimer Disease and Dementia, run by Eli Lilly and Company at 27 sites in 2 countries.

Completed

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

Official record

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Trial summary

The main goals of this study are to further determine whether the study drug donanemab is safe and effective in participants with Alzheimer's disease and to validate neuropsychological assessments administered over videoconferencing Read more about this study

Who is it for?
Ages 60 to 90 years
Conditions the study is for
Alzheimer Disease, Dementia, Brain Diseases
What is being tested?
donanemab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
27 sitesin 2 countries
Study dates
23 Nov 2020to 27 Feb 2024
Phase
Phase 2

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 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participated in a double-blind treatment period of a sponsor-approved originating donanemab trial, for example the TRAILBLAZER-ALZ study.
  • Have a study partner
  • Stable symptomatic Alzheimer's Disease (AD) medications and other medication that may impact cognition for at least 30 days prior to randomization into Part A

Who cannot join

  • Current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with outcome assessments or the analyses in this study.
  • Have received treatment with a passive anti-amyloid immunotherapy after completion of originating donanemab study or received active immunization against Aβ in any other study.
  • Poor venous access
  • Contraindication to PET or MRI imaging

Trial locations and contacts

27 sites in 2 countries.

27 sites in 2 countries

United States23 sites
  • Abington Neurological Associates, Ltd.

    Abington, Pennsylvania, 19001

  • Bradenton Research Center, Inc.

    Bradenton, Florida, 34205

  • Ohio State University

    Columbus, Ohio, 43210

  • Neurology Diagnostics, Inc.

    Dayton, Ohio, 45459

  • The University of Kansas - Clinical Research Center

    Fairway, Kansas, 66205

  • Guilford Neurologic Research, PA

    Greensboro, North Carolina, 27405

  • Indiana University

    Indianapolis, Indiana, 46202

  • Josephson Wallack Munshower Neurology, PC

    Indianapolis, Indiana, 46256

  • UC Irvine-Institute for Memory Impairments and Neurological Disorders (UCI MIND)

    Irvine, California, 92697

  • Las Vegas Medical Research

    Las Vegas, Nevada, 89113

  • Merritt Island Medical Research, LLC

    Merritt Island, Florida, 32952

  • Boston Center for Memory

    Newton, Massachusetts, 02459

  • Synexus Clinical Research US, Inc.

    Orlando, Florida, 32806

  • Advanced Research Consultants

    Palm Beach Gardens, Florida, 33410

  • Banner Alzheimer's Institute

    Phoenix, Arizona, 85006

  • Progressive Medical Research

    Port Orange, Florida, 32127

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • National Clinical Research, Inc

    Richmond, Virginia, 23294

  • Intercoastal Medical Group - Hyde Park

    Sarasota, Florida, 34239

  • Washington University

    St Louis, Missouri, 63110

  • Stedman Clinical Trials

    Tampa, Florida, 33613

  • Advanced Memory Research Institute of New Jersey

    Toms River, New Jersey, 08755

  • Cotton O'Neil Clinical Research Center - Central Office

    Topeka, Kansas, 66606

Other trials in United States

Canada4 sites
  • Clinique de la Mémoire de l'Outaouais

    Gatineau, Quebec, J8T 8J1

  • Bruyère Research Institute

    Ottawa, Ontario, K1N 5C8

  • Diex Recherche Sherbrooke Inc.

    Sherbrooke, Quebec, J1L 0H8

  • Toronto Memory Program

    Toronto, Ontario, M3B 2S7

Other trials in Canada

About this study

Official title: Donanemab Follow-On Study: Safety, Tolerability, And Efficacy in Symptomatic Alzheimer's Disease With Validation of Remote Neuropsychological Assessments

The main goals of this study are to further determine whether the study drug donanemab is safe and effective in participants with Alzheimer's disease and to validate neuropsychological assessments administered over videoconferencing

Being tested
No Intervention, donanemab
Medical subject headings
Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Cognitive Dysfunction

What participants receive

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

  • No InterventionOther

    No intervention

  • donanemabDrug

    Also called LY3002813

    Administered IV

Study groups in NCT04640077
Study groupRoleWhat they receive
Part A: Validation of Remote Scale AssessmentsOtherParticipants from the originating trials did not receive any drug in Part A. Participants were randomized 1:1 into two groups to have their cognitive and functional scales assessed. Group 1: Cognitive/functional scale assessment at the study site (on-site), followed by an at-home assessment (VTC; video teleconference), or Group 2: Cognitive/functional scale assessment at home (VTC), followed by assessment on-site. Total time in Part A was up to 24 weeks.
Receives: Other: No Intervention
Part B: DonanemabExperimentalParticipants who had received placebo in the originating trials received 700 milligrams (mg) donanemab administered intravenously (IV) every 4 weeks (Q4W) for 3 doses, then 1400 mg donanemab administered IV Q4W for up to 48 weeks.
Receives: Drug: donanemab

What is being measured

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

  1. Part A: Intraclass Correlation Between On-Site and Video Teleconference (VTC) Assessments

    Part A didn't involve any drug and drug related efficacy analyses. Participants in Part A were divided into 2 groups, and they completed the same set of clinical assessments. Participants in Part A Group 1 completed the clinical assessments at a clinic site first (on-site) followed by at home assessments (VTC). Participants in Part A Group 2 completed the assessments at home first, followed by on-site assessment. The goal of Part A was to evaluate the comparability of remote and on-site clinical assessments. The intra-class correlation coefficient (ICC), a measure of agreement for continuous outcome measures, was used to determine agreement between remote and onsite assessments for each outcome measure. Outcome measure tested were the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog13), Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL), Mini Mental State Examination (MMSE), and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB).

    Measured: Baseline to 4 Weeks

  2. Part B: Percentage of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Percentage of participants with TEAEs and SAEs were reported here. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this record.

    Measured: Baseline Up To 96 Weeks

  3. Part B: Number of Participants With Suicidality Based on Columbia-Suicide Severity Rating Scale (C-SSRS)

    Number of Participants with Suicidality Based on C-SSRS was reported.

    Measured: Baseline, Week 72

Secondary outcomes (9)
  1. Part B: Change From Baseline on the Mini Mental State Examination (MMSE) Score

    The MMSE is an instrument used to assess cognitive function in participants. The instrument measures orientation, memory, and attention; the ability of the participant to name objects; follow verbal and written commands; write a sentence; and copy figures. The range for the total MMSE score is 0 to 30, with lower scores indicating greater level of impairment. LS Mean was determined by Mixed Models for Repeated Measurements (MMRM) model with Baseline + Visit + Baseline*Visit + Age + Years of Education + Presence/ Absence of Anti-dementia Drugs as variables.

    Measured: Baseline, Week 72

  2. Part B: Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score

    The ADAS-Cog13 (13-item version of ADAS Cog) assesses areas of cognitive function that are the most typically impaired in Alzheimer's Disease (AD): orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze-completion measures. The ADAS-Cog13 scale ranges from 0 to 85, with higher scores indicating greater disease severity. LS Mean was determined by MMRM model with Baseline + Visit + Baseline*Visit + Age + Years of Education + Presence/Absence of Anti-dementia Drugs as variables.

    Measured: Baseline, Week 72

  3. Part B: Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS)

    The iADRS is a composite that measures both cognition and function from the ADAS-Cog and the ADCS-iADL (Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living). The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with lower scores indicating greater impairment. LS Mean was determined by MMRM model using Baseline + Visit + Baseline*Visit + Age + Years of Education + Presence/Absence of Anti-dementia Drugs as variables.

    Measured: Baseline, Week 72

  4. Part B: Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL)

    The ADCS-iADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM model using = Baseline + Visit + Baseline*Visit + Age + Years of Education + Presence/Absence of Anti-dementia Drugs as variables.

    Measured: Baseline, Week 72

  5. Part B: Change From Baseline on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)

    The CDR-SB is a global assessment tool than can be used to effectively evaluate both cognition and function. Participant's cognitive status is rated across 6 domains or 'boxes' of functioning: Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, and Personal Care. The CDR-SB scores are calculated by adding the box scores and range from 0 to 18 with higher scores indicative of more impairment. LS Mean was determined by MMRM model using Baseline + Visit + Baseline*Visit + Age + Years of Education + Presence/Absence of Anti-dementia Drugs as variables.

    Measured: Baseline, Week 72

  6. Part B: 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 36 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. LS Mean was determined by ANCOVA model using originating study's Baseline + Age + Treatment (Type III sum of squares) as variables.

    Measured: Baseline, Week 36

  7. Part B: Change From Baseline in Whole Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)

    Change from Baseline in Whole Brain Volume as Measured by vMRI in Part B. LS mean were derived using MMRM model with fixed factors for visit, and covariates for baseline score, and age at baseline.

    Measured: Baseline, Week 72

  8. Part B: Pharmacokinetics (PK): Trough Concentrations of Donanemab (Ctrough)

    PK: Trough Concentration of donanemab. Ctrough is the concentration of drug in the blood immediately before the next dose of drug was administered.

    Measured: Predose at Week 8 and Week 16

  9. Part B: Number or Participants With Treatment-Emergent Anti-Drug Antibodies (TE ADA) of Donanemab

    Number of participants in Part B with positive Anti-drug antibodies (TE ADA+) was reported. A TE ADA evaluable participant is classified as TE ADA+ if they have at least one postbaseline titer that is 4 times or more higher than the baseline titer (treatment-boosted). If the baseline result is ADA Not Present, the subject is considered TE ADA+ if there is at least one postbaseline result showing ADA present with a titer of 1:10 or higher (treatment-induced).

    Measured: Baseline, 4, 8, 16, 24, 36, 48, 60, 72, 84, and 96 Weeks

Timeline

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

  1. First posted23 Nov 2020
  2. Study start23 Nov 2020
  3. Primary completion27 Feb 2024
  4. Study completion27 Feb 2024

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04640077
Sponsor's protocol ID
17447
Other IDs
I5T-MC-AACH
Status last verified
May 2025
First submitted
9 Nov 2020
Last updated
13 Jun 2025
Data monitoring committee
No
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

  • 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

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