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

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

Study Overview

• Status: Completed
• Conditions: Brain Diseases; Central Nervous System Diseases; Cognitive Impairment; Dementia; Alzheimer Disease
• Intervention / Treatment: Other: No Intervention; Drug: donanemab

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1N 5C8
      • Bruyere Research Institute
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Clinique de la Memoire de l'Outaouais
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • DIEX Recherche Sherbrooke Inc.
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
  • California
    • Irvine, California, United States, 92697
      • UC Irvine-Institute for Memory Impairments and Neurological Disorders (UCI MIND)
  • Florida
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center, Inc.
    • Merritt Island, Florida, United States, 32952
      • Merritt Island Medical Research, LLC
    • Orlando, Florida, United States, 32806
      • Synexus Clinical Research US, Inc.
    • Palm Beach Gardens, Florida, United States, 33410
      • Advanced Research Consultants
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Sarasota, Florida, United States, 34239
      • Intercoastal Medical Group - Hyde Park
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology, PC
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas - Clinical Research Center
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center - Central Office
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas Medical Research
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of New Jersey
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Guilford Neurologic Research, PA
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics, Inc.
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates, Ltd.
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Part A: Validation of Remote Scale Assessments; 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.	Other: No Intervention; No intervention
Experimental: Part B: Donanemab; 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.	Drug: donanemab; Administered IV; Other Names: LY3002813

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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.	Baseline, Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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).	Baseline, 4, 8, 16, 24, 36, 48, 60, 72, 84, and 96 Weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Actual): February 27, 2024
• Study Completion (Actual): February 27, 2024

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): June 13, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Brain Diseases; Nervous System Diseases; Central Nervous System Diseases
• Other Study ID Numbers: 17447; I5T-MC-AACH (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

Access Criteria:

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No