A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)

Study Overview
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Brief Summary
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The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer's disease. Additional participants will be enrolled to an addendum safety cohort. The participants will be administered open-label donanemab.

Detailed Description
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TRAILBLAZER-ALZ 2 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of N3pG antibody (donanemab) in participants with early symptomatic AD (prodromal AD and mild dementia due to AD) with the presence of brain tau pathology. Following the double-blind 76-week main study period, a double-blind 78-week long-term extension period is added to further evaluate donanemab efficacy and safety over time. Participants from the addendum safety cohort are not eligible for the extension period.

Official Title
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Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: Donanemab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months MMSE score of 20 to 28 (inclusive) at baseline Meet 18F flortaucipir PET scan (central read) criteria - does not apply to safety cohort Meet 18F florbetapir PET scan (central read) criteria Have a study partner who will provide written informed consent to participate Exclusion Criteria: Contraindication to MRI or PET scans Current treatment with immunoglobulin G (IgG) therapy

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donanemab<br>Donanemab given intravenously (IV). | Drug: Donanemab<br>* Given IV<br>* Other names: LY3002813;|
| Placebo Comparator: Placebo<br>Placebo given IV. | Drug: Placebo<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline on the integrated Alzheimer's Disease Rating Scale (iADRS) | Change from Baseline on the iADRS in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Up to Week 76 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline on the Mini Mental State Examination (MMSE) Score | Change from Baseline on the MMSE Score in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Up to Week 76 | 
| Change from Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) | Change from Baseline on the ADAS-Cog13 in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population' | Baseline, Up to Week 76 | 
| Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) | Change from Baseline on the CDR-SB in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Up to Week 76 | 
| Change from Baseline on the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) Score | Change from Baseline on the ADCS-iADL Score in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'. | Baseline, Up to Week 76 | 
| 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, Up to Week 76 | 
| Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan | Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan | Baseline, Up to Week 76 | 
| Change from Baseline in Brain Volume as Measured by volumetric Magnetic Resonance Imaging (vMRI) | Change from Baseline in Brain Volume as Measured by vMRI | Baseline, Up to Week 76 | 
| Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab | PK: Average Serum Concentration at steady state of Donanemab | Baseline through Week 76 | 
| Number or Participants with Anti-Donanemab Antibodies | Number or Participants with Anti-Donanemab Antibodies | Baseline through Week 76 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's, Dementia, Cognitive Impairment, Amyloid Plaque