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
Drug: donanemab

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 neuropsychological assessments administered over videoconferencing

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 95

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

Group	Intervention	Description
Part A: Validation of Remote Scale Assessments	No Intervention	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.
Part B: Donanemab	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.

Primary Outcome Measures

Name	Time	Method
Part A: Intraclass Correlation Between On-Site and Video Teleconference (VTC) Assessments	Baseline to 4 Weeks	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).
Part B: Number of Participants With Suicidality Based on Columbia-Suicide Severity Rating Scale (C-SSRS)	Baseline, Week 72	Number of Participants with Suicidality Based on C-SSRS was reported.
Part B: Percentage of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Baseline Up To 96 Weeks	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.

Secondary Outcome Measures

Name	Time	Method
Part B: Change From Baseline on the Mini Mental State Examination (MMSE) Score	Baseline, Week 72	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.
Part B: Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) Score	Baseline, Week 72	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.
Part B: Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS)	Baseline, Week 72	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.
Part B: Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL)	Baseline, Week 72	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.
Part B: Change From Baseline on the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB)	Baseline, Week 72	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.
Part B: Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan	Baseline, Week 36	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.
Part B: Change From Baseline in Whole Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)	Baseline, Week 72	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.
Part B: Pharmacokinetics (PK): Trough Concentrations of Donanemab (Ctrough)	Predose at Week 8 and Week 16	PK: Trough Concentration of donanemab. Ctrough is the concentration of drug in the blood immediately before the next dose of drug was administered.
Part B: Number or Participants With Treatment-Emergent Anti-Drug Antibodies (TE ADA) of Donanemab	Baseline, 4, 8, 16, 24, 36, 48, 60, 72, 84, and 96 Weeks	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).

Trial Locations

Locations (27): Banner Alzheimer's Institute
🇺🇸
Phoenix, Arizona, United States
UC Irvine-Institute for Memory Impairments and Neurological Disorders (UCI MIND)
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Irvine, California, United States
Bradenton Research Center, Inc.
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Bradenton, Florida, United States
Merritt Island Medical Research, LLC
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Merritt Island, Florida, United States
Synexus Clinical Research US, Inc.
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Orlando, Florida, United States
Advanced Research Consultants
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Palm Beach Gardens, Florida, United States
Progressive Medical Research
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Port Orange, Florida, United States
Intercoastal Medical Group - Hyde Park
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Sarasota, Florida, United States
Stedman Clinical Trials
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Tampa, Florida, United States
Indiana University
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Indianapolis, Indiana, United States
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Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States