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

Phase 2
Completed
Conditions
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Cognitive Impairment
Interventions
Other: No Intervention
Registration Number
NCT04640077
Lead Sponsor
Eli Lilly and Company
Brief 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 video scale assessments.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
94
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part A Validation of Remote Scale AssessmentsNo InterventionAlternating 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
Part B DonanemabdonanemabDonanemab administered intravenously (IV)
Primary Outcome Measures
NameTimeMethod
Part A: Correlation between VTC and on-site assessment for PAIR 1 for Mini Mental State Examination (MMSE) Score1 Month

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.

Part A: Correlation between VTC and on-site assessment for PAIR 1 for Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)1 Month

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.

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)1 Month

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.

Part A: Correlation between VTC and on-site assessment for PAIR 1 for Clinical Dementia Rating-Sum of Boxes (CDR-SB)1 Month

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).

Part B: Percentage of Participants with One or More Adverse Events (AEs) or Serious AEsUp to 72 Weeks

A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Secondary Outcome Measures
NameTimeMethod
Part B: Change from Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS)Baseline, Week 72

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.

Part B: Change from Baseline on the ADCS-iADLBaseline, Week 72

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.

Part B: Change from Baseline on the CDR-SBBaseline, Week 72

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).

Part B: Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) ScanBaseline, Week 72

Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 PET Scan

Part B: Change from Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) measuresBaseline, Week 72

Change from Baseline in Brain Volume as Measured by vMRI

Part B: Pharmacokinetics (PK): Average Serum Concentration of DonanemabPredose, Up to Week 72

PK: Average Serum Concentration of donanemab

Part B: Number or Participants with Anti-Donanemab AntibodiesBaseline to Week 72

Number or Participants with Anti-donanemab Antibodies

Part B: Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)Baseline, Week 72

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).

Part B: Change from Baseline on the MMSE ScoreBaseline, Week 72

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.

Part B: Change from Baseline on the ADAS-Cog13 scoreBaseline, Week 72

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.

Trial Locations

Locations (27)

Bradenton Research Center, Inc.

🇺🇸

Bradenton, Florida, United States

Merritt Island Medical Research, LLC

🇺🇸

Merritt Island, Florida, United States

Boston Center for Memory

🇺🇸

Newton, Massachusetts, United States

Cotton O'Neil Clinical Research Center - Central Office

🇺🇸

Topeka, Kansas, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Stedman Clinical Trials

🇺🇸

Tampa, Florida, United States

The University of Kansas - Clinical Research Center

🇺🇸

Fairway, Kansas, United States

Clinique de la Mémoire de l'Outaouais

🇨🇦

Gatineau, Quebec, Canada

Toronto Memory Program

🇨🇦

Toronto, Ontario, Canada

Bruyère Research Institute

🇨🇦

Ottawa, Ontario, Canada

Abington Neurological Associates, Ltd.

🇺🇸

Abington, Pennsylvania, United States

Banner Alzheimer's Institute

🇺🇸

Phoenix, Arizona, United States

Las Vegas Medical Research

🇺🇸

Las Vegas, Nevada, United States

Josephson Wallack Munshower Neurology, PC

🇺🇸

Indianapolis, Indiana, United States

Diex Recherche Sherbrooke Inc.

🇨🇦

Sherbrooke, Quebec, Canada

National Clinical Research, Inc

🇺🇸

Richmond, Virginia, United States

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

🇺🇸

Irvine, California, United States

Advanced Research Consultants

🇺🇸

Palm Beach Gardens, Florida, United States

Advanced Memory Research Institute of New Jersey

🇺🇸

Toms River, New Jersey, United States

Ohio State University

🇺🇸

Columbus, Ohio, United States

Guilford Neurologic Research, PA

🇺🇸

Greensboro, North Carolina, United States

Neurology Diagnostics, Inc.

🇺🇸

Dayton, Ohio, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Intercoastal Medical Group - Hyde Park

🇺🇸

Sarasota, Florida, United States

Progressive Medical Research

🇺🇸

Port Orange, Florida, United States

Synexus Clinical Research US, Inc.

🇺🇸

Orlando, Florida, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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