A Study of Donanemab (LY3002813) Compared With Aducanumab in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ 4)

Lilly

Status and phase: Completed; Phase 3

Conditions: Mild Cognitive Impairment (MCI); Alzheimer Disease

Treatments: Drug: Aducanumab; Drug: Donanemab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05108922

18369

I5T-MC-AACN (Other Identifier)

Details and patient eligibility

About

The main purpose of this study is to compare donanemab to aducanumab on brain amyloid plaque clearance in participants with early symptomatic Alzheimer's Disease (AD).

Enrollment: 148 patients

Sex: All

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Gradual and progressive change in memory function reported by the participant or informant for ≥6 months.
• Meet florbetapir F18 PET scan criteria.
• A Clinical Dementia Rating (CDR)-Global Score of 0.5 or 1.
• Must consent to apolipoprotein E (ApoE) genotyping
• Must have a mini mental state examination (MMSE) score between 20 and 30
• Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to study visits or be available by telephone at designated times.
• Have adequate literacy, vision, and hearing for neuropsychological testing in the opinion of the investigator at the time of screening.
• Women not of childbearing potential may participate

Exclusion criteria

• Significant neurological disease affecting the central nervous system (other than AD), that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, history of transient ischemic attack or stroke, or epilepsy or recurrent seizures (except febrile childhood seizures).

• Current serious or unstable medical illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, psychiatric (including actively suicidal or deemed at risk of suicide, or current alcohol or substance abuse), immunologic, infectious, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study; or has a life expectancy of approximately

  ≤24 months.

• History of clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions (including but not limited to erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, and/or exfoliative dermatitis).

• History of bleeding disorder or use of medications with platelet anti-aggregant or anti-coagulant properties (unless aspirin at ≤325 milligram (mg).

• Have had prior or current treatment with donanemab or aducanumab

• Have known allergies to donanemab or aducanumab, related compounds, or any components of the formulation

• Prior or current participation in any immunotherapy study targeting Amyloid beta

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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148 participants in 2 patient groups

Donanemab

Experimental group

Description:

Donanemab is administered intravenously (IV) every 4 weeks (Q4W).

Treatment:

Drug: Donanemab

Aducanumab

Active Comparator group

Description:

Aducanumab administered IV per US label.

Treatment:

Drug: Aducanumab