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.
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
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
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
- Conditions
- Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Cognitive Impairment
- 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 group | Role | What they receive |
|---|---|---|
| Part A: Validation of Remote Scale Assessments | Other | Participants 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: Donanemab | Experimental | Participants 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.
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
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
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)
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
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
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
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
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
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
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
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
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.
- First posted23 Nov 2020
- Study start23 Nov 2020
- Primary completion27 Feb 2024
- Study completion27 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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 41804324Gueorguieva 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