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 video scale assessments.

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): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1N 5C8
      • Bruyère Research Institute
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Clinique de la Mémoire 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; Alternating at-home and on-site cognitive and functional scale assessments 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	Other: No Intervention; No intervention
Other: Part B Donanemab; Donanemab administered intravenously (IV)	Drug: donanemab; Administered IV; Other Names: LY3002813

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Correlation between VTC and on-site assessment for PAIR 1 for Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)	Correlation between VTC and on-site assessment for PAIR 1 (defined as completing a VTC evaluation and one in person evaluation regardless of order) for the ADAS-Cog13. The ADAS-Cog13 (13-item version of ADAS Cog) assesses areas of cognitive function that are the most typically impaired in 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.	1 Month
Part A: Correlation between VTC and on-site assessment for PAIR 1 for Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL)	Correlation between VTC and on-site assessment for PAIR 1 for ADCS-ADL. 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 of daily living by participants. The range for the total ADCS-ADL score is 0 to 78, with lower scores indicating greater level of impairment. Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) is calculated from a subset of questions from the ADCS-ADL. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance.	1 Month
Part A: Correlation between VTC and on-site assessment for PAIR 1 for Mini Mental State Examination (MMSE) Score	Correlation between VTC and on-site assessment for PAIR 1 for MMSE. The MMSE is a brief instrument used to assess cognitive function in participants. The range for the total MMSE score is 0 to 30, with lower scores indicating greater level of impairment.	1 Month
Part A: Correlation between VTC and on-site assessment for PAIR 1 for Clinical Dementia Rating-Sum of Boxes (CDR-SB)	Correlation between VTC and on-site assessment for PAIR 1 for CDR-SB. The CDR-SB is a global assessment tool than can be used to effectively evaluate both cognition and function. The CDR-SB scores are calculated by adding the box scores and range from 0 to 18 (with higher scores indicative of more impairment).	1 Month
Part B: Percentage of Participants with One or More Adverse Events (AEs) or Serious AEs	A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.	Up to 72 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B: Change from Baseline on the MMSE Score	Change from Baseline on the MMSE Score. The MMSE is a brief instrument used to assess cognitive function in participants. The range for the total MMSE score is 0 to 30, with lower scores indicating greater level of impairment.	Baseline, Week 72
Part B: Change from Baseline on the ADAS-Cog13 score	Change from Baseline on the ADAS-Cog13. The ADAS-Cog13 (13-item version of ADAS Cog) assesses areas of cognitive function that are the most typically impaired in 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.	Baseline, Week 72
Part B: Change from Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS)	Change from Baseline on the iADRS. The iADRS is a composite that measures both cognition and function from the ADAS- Cog and the ADCS-iADL. 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.	Baseline, Week 72
Part B: Change from Baseline on the ADCS-iADL	Change from Baseline on the ADCS-iADL. 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 of daily living by participants. The range for the total ADCS-ADL score is 0 to 78, with lower scores indicating greater level of impairment. ADCS-iADL is calculated from a subset of questions from the ADCS-ADL. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance.	Baseline, Week 72
Part B: Change from Baseline on the CDR-SB	Change from Baseline on the CDR-SB. The CDR-SB is a global assessment tool than can be used to effectively evaluate both cognition and function. The CDR-SB scores are calculated by adding the box scores and range from 0 to 18 (with higher scores indicative of more impairment).	Baseline, Week 72
Part B: Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan	Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 PET Scan	Baseline, Week 72
Part B: Change from Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) measures	Change from Baseline in Brain Volume as Measured by vMRI	Baseline, Week 72
Part B: Pharmacokinetics (PK): Average Serum Concentration of Donanemab	PK: Average Serum Concentration of donanemab	Predose, Up to Week 72
Part B: Number or Participants with Anti-Donanemab Antibodies	Number or Participants with Anti-donanemab Antibodies	Baseline to Week 72
Part B: Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)	Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a scale that captures the occurrence, severity, and frequency of suicidal ideation and behavior during the assessment period via a questionnaire. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity).	Baseline, Week 72

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): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Nervous System Diseases; Alzheimer Disease; Brain 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