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

Study Overview
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Brief Summary
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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.

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

Conditions
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Alzheimer Disease, Dementia, Brain Diseases, Central Nervous System Diseases, Cognitive Impairment

Intervention / Treatment
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* Other: No Intervention
* Drug: donanemab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Part A Validation of Remote Scale Assessments<br>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<br>* No intervention<br>|
| Other: Part B Donanemab<br>Donanemab administered intravenously (IV) | Drug: donanemab<br>* Administered IV<br>* Other names: LY3002813;|

What is the study measuring?
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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 |