The main purpose of this study is to evaluate the safety and efficacy of donanemab in participants with preclinical Alzheimer's Disease (AD) over up to 332 weeks. Approximately 800 additional participants will be enrolled in the 12-month Addendum 7 to assess safety of a different titration regimen.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
2,996
Time to Clinical Progression of Composite Endpoint as Measured by Clinical Dementia Rating (CDR) in the Primary Study Population (Baseline CDR-Global Score [GS 0])
Time to clinical progression as measured by CDR. CDR is a clinician-rated scale that provides an overall assessment of the participant's stage on the spectrum of Alzheimer's Disease (AD) dementia
Time frame: Estimated up to Week 332
Change from Baseline in Cognitive Composite in the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in Cognitive Composite in the Primary Study Population (CDR-GS 0)
Time frame: Baseline, Up to Week 332
Change from Baseline in International Shopping List Test (ISLT) in the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in clinical progression as measured by ISLT in the Primary Study Population (Baseline CDR-GS 0)
Time frame: Baseline, Up to Week 332
Change from Baseline in Continuous Paired Associate Learning (CPAL ) in the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in clinical progression as measured by CPAL in the Primary Study Population (baseline CDR-GS 0)
Time frame: Baseline, Up to Week 332
Change from Baseline in International Daily Symbol Substitution Test-Medicines (iDSSTm) in the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in clinical progression as measured by iDSSTm in the Primary Study Population (Baseline CDR-GS 0)
Time frame: Baseline, Up to Week 332
Change from Baseline in Category Fluency in the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in clinical progression as measured by Category Fluency in the Primary Study Population (Baseline CDR-GS 0)
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Parkway Medical Center
Birmingham, Alabama, United States
Alabama Psychiatry - Birmingham - Brookwood Medical Center Drive
Homewood, Alabama, United States
Rehabilitation & Neurological Services
Huntsville, Alabama, United States
Care Access - 801 South Power Road, Mesa
Mesa, Arizona, United States
Banner Alzheimer's Institute
Phoenix, Arizona, United States
Banner Alzheimer's Institute Tucson
Tucson, Arizona, United States
Center for Neurosciences
Tucson, Arizona, United States
Care Access - Berkeley
Berkeley, California, United States
Care Access - Beverly Hills
Beverly Hills, California, United States
Velocity Clinical Research, Chula Vista
Chula Vista, California, United States
...and 206 more locations
Time frame: Baseline, Up to Week 332
Change from Baseline in CDR-Sum of Boxes (CDR-SB) n the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in clinical progression as measured by CDR-SB in the Primary Study Population (Baseline CDR-GS 0)
Time frame: Baseline, Up Week 332
Change from Baseline in Cognitive Function Index (CFI) in the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in clinical progression as measured by CFI in the Primary Study Population (Baseline CDR-GS 0)
Time frame: Baseline, Up to Week 332
Change from Baseline in Montreal Cognitive Assessment (MoCA) Score in the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in clinical progression as measured by MoCA score in the Primary Study Population (Baseline CDR-GS 0)
Time frame: Baseline, Up to Week 332
Change from Baseline in Mild Behavioral Impairment Checklist (MBI-C) in the Primary Study Population (Baseline CDR-GS 0)
Change from baseline in MBI-C in the Primary Study Population (Baseline CDR-GS 0)
Time frame: Baseline, Up to Week 332
Time to Clinical Progression of Composite Endpoint as Measured by CDR in the Overall Study Population (Baseline CDR-GS 0 or 0.5)
Time to clinical progression as measured by CDR in the Overall Study Population (Baseline CDR-GS 0 or 0.5)
Time frame: Baseline, Up to Week 332
Time to Clinical Progression as Measured by CDR Memory Box in Primary Study Population (Baseline CDR-GS 0)
Time to clinical progression as measured by CDR Memory Box in the Primary Study Population (Baseline CDR-GS 0)
Time frame: Estimated up to Week 332
Time to Clinical Progression as Measured by CDR Judgment and Problem Solving Box in the Primary Study Population (Baseline CDR-GS 0)
Time to clinical progression as measured by CDR Judgment and Problem Solving Box in the Primary Study Population (Baseline CDR-GS 0)
Time frame: Estimated up to Week 332
Time to Clinical Progression as Measured by At Least 0.5 Change on CDR-SB in Primary Study Population (Baseline CDR-GS 0)
Time to clinical progression as measured by at least 0.5 change on CDR-SB in Primary Study Population (Baseline CDR-GS 0)
Time frame: Estimated up to Week 332
Time to Clinical Progression of Composite Endpoint as Measured by CDR in Subpopulation Positive Based on Secondary Diagnostic Test
Time to clinical progression as measured by CDR in subpopulation positive based on secondary diagnostic test
Time frame: Estimated up to Week 332
Change from Baseline in Plasma P-tau217
Change from baseline in Plasma P-tau217
Time frame: Baseline, Up to Week 332
Pharmacokinetics (PK): Average Serum Donanemab Concentration at Steady State
PK: Average serum donanemab concentration at steady state
Time frame: Baseline through Week 76
Percentage of Participants with Treatment-emergent Anti-Drug Antibody (ADAs)
Percentage of participants with treatment-emergent anti-drug antibody (ADAs)
Time frame: Baseline through Week 16