A Real-World Comparative Study of Donanemab (LY3002813) Plus Usual Care Versus Usual Care Alone in US Participants With Early Symptomatic Alzheimer's Disease

Long-Term Real-World Comparative Effectiveness of Donanemab Plus Usual Care Versus Usual Care Alone in US Patients With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-REAL US)

The main purpose of this study is to evaluate the long-term effectiveness of donanemab plus usual care versus usual care alone in participants with early symptomatic AD. The study will employ a prospective, observational cohort design with participant management resembling real-world practice to the greatest extent possible via prospective assessments and linkage to historical and prospective electronic health records. The study will last about 273 weeks and may include up to 28 visits.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Donanemab; Drug: Usual Care

• Study Type: Observational
• Enrollment (Estimated): 6250

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: clinical_inquiry_hub@lilly.com

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805-4046
      • Recruiting
      • Rehabilitation & Neurological Services
      • Principal Investigator: Belinda Savage-Edwards

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of a donanemab plus usual care group and a usual care alone group. Participants will be enrolled 1:2 into donanemab plus usual care and usual care alone groups to allow enough participants in the usual care group to be matched with participants in the donanemab group to enable robust comparative effectiveness analyses.

Description

Inclusion Criteria:

Participants

• are under care for presumed mild cognitive impairment (MCI) or mild dementia stage of AD (Note: neither a biomarker-based diagnosis of AD nor a diagnosis in electronic health records [EHR] is required prior to screening)
• have a Telephone Interview for Cognitive Status (TICS) score of ≥21
• presence of amyloid beta (Aβ) pathology supported by biomarker results (e.g., P-tau, amyloid positron emission tomography (PET), and/or cerebrospinal fluid [CSF]). (Note: A historical biomarker may be used for eligibility if performed within 12 months of study entry)
• have a reliable study partner who is in frequent contact with the participant and will be available by telephone at designated times (every 6 months), and
• have EHR data available for linkage and are willing to allow access to EHR data for the duration of the study.

Exclusion Criteria:

• have prior ischemic or hemorrhagic stroke(s) with an inability to independently perform any one or more basic activities of daily living (ADLs) (i.e., walking, transferring, eating, bathing, dressing, or toileting). (Note: mixed dementias with amyloid pathology are permitted)
• have current or recent serious or unstable illness (other than AD) that, in the investigator's opinion, could interfere with the ability of the participant or study partner to complete the study (e.g., life expectancy of less than 36 months, requirement for long-term (>12 months) institutional-level care, serious psychiatric illness, etc.)
• are currently enrolled or intend to enroll in a clinical trial of another investigational product, and
• have contraindications to donanemab, magnetic resonance imaging (MRI), or amyloid PET tracers. (Donanemab group only).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Donanemab Group + Usual Care; Participants will receive open-label (unblinded) donanemab intravenously (IV) and Usual Care	Drug: Donanemab; Administered IV; Other Names: LY3002813; Drug: Usual Care; Medication (excluding amyloid-targeting agents) or non-pharmacological therapy including watchful waiting.
Usual Care Group; Participants will receive usual care.	Drug: Usual Care; Medication (excluding amyloid-targeting agents) or non-pharmacological therapy including watchful waiting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Increase in Dependence Level Above Baseline (as derived from the Dependence Scale [DS])	The DS is a caregiver-reported outcome assessing the need for daily in-home or institutional assistance by participants with AD. The DS is completed as a structured interview with a knowledgeable caregiver or study partner. The scale is composed of 13 items evaluating progressive needs for assistance. The total score ranges from 0 to 15, with higher scores indicating a greater degree of dependence on external support.	Up to 5 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Loss of Independence (Dependence Level ≥3 as derived from the DS) for the Subgroup of Participants with Dependence Level <3 at Baseline		Up to 5 Years
Time to Institutionalization from Baseline for the Subgroup of Participants not Institutionalized at Baseline	Participants who endorse, "Assisted living facility" or "Skilled nursing facility, nursing home, hospice" as their primary residence on the participant lifestyle status Questionnaire (P-LSQ) will be considered institutionalized.	Up to 5 Years
Change from Baseline Over Time (Semi-Annually) in DS Total Score		Baseline, Up to 5 Years
Change from Baseline Over Time (Assessed Semi-Annually) in Functional Assessment Questionnaire (FAQ) Total Score	The FAQ is a brief, 10-item caregiver-reported outcome measure assessing performance on functional activities impacted early during AD. The maximum total score is 30, with higher scores indicating greater impairment.	Baseline, Up to 5 Years
Change from Baseline Over Time (Assessed Yearly) in Neuropsychiatric Inventory (NPI-Q) Total Severity Score	The NPI-Q is a brief, caregiver-reported assessment of neuropsychiatric symptoms associated with dementia. The NPI-Q yields total scores for Severity and Distress, reflecting the sum of ratings across all domains, with higher scores indicating a greater degree of symptom severity and caregiver distress, respectively.	Baseline, Up to 5 Years
Change from Baseline Over Time (Assessed Yearly) in Zarit Burden Inventory-short version (ZBI-12) total score	ZBI is a caregiver-reported instrument used widely to evaluate caregiver burden associated with AD and other diseases such as multiple sclerosis, congestive heart failure, and cancer. Items on the ZBI-12 assess caregiver stress, time available for self, and the impact of caring on the caregiver's social life. Responses are provided on a 5-point Likert scale (never=0, nearly always=4). The ZBI-12 total score has a range of 0 to 48, with higher scores indicating greater caregiver burden.	Baseline, Up to 5 Years
Change from Baseline Over Time (Assessed Semi-Annually) in Living Situation as Assessed by the Participant Lifestyle Questionnaire (P-LSQ)	The P-LSQ is a brief, sponsor-created questionnaire used to collect supplementary data regarding participants' living environment, home healthcare needs, and driving status that is not captured elsewhere.	Baseline, Up to 5 Years
Change from Baseline Over Time (Assessed Semi-Annually) in Home Healthcare as Assessed by the P-LSQ		Baseline, Up to 5 Years
Change from Baseline Over Time (Assessed Semi-Annually) in Driving Status as Assessed by the P-LSQ		Baseline, Up to 5 Years

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

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2024
• Primary Completion (Estimated): February 1, 2033
• Study Completion (Estimated): February 1, 2033

Study Registration Dates

• First Submitted: August 20, 2024
• First Submitted That Met QC Criteria: August 20, 2024
• First Posted (Actual): August 22, 2024

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; donanemab
• Other Study ID Numbers: 18721; I5T-MC-AACS (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 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