Alzheimer Disease
Conditions
Brief summary
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.
Interventions
DRUGDonanemab
Administered intravenously
DRUGPlacebo
Administered intravenously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* A Telephone Interview for Cognitive Status - modified (TICS-M) score reflective of intact cognitive functioning. * Has a phosphorylated tau (P-tau) result consistent with the presence of amyloid pathology. * Has a reliable study partner and backup study partner familiar with overall function and behavior, such as day-to-day activities and cognitive abilities. * Have adequate literacy, vision, and hearing for neuropsychological testing at screening. * Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies * Female participants include those who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis; or post menopausal (women 55 or older not on hormone therapy and had at least 12 months of spontaneous amenorrhea; or with a diagnosis of menopause prior to starting hormone replacement therapy. Treatment Extension: (Study Period II Placebo Group Only) * Are actively participating in Study AACM at the conclusion of Study Period III.
Exclusion criteria
* Mild cognitive impairment or dementia, or significant other neurodegenerative disease that can affect cognition. * Current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease that could interfere with the analysis of the study or a life expectancy of approximately ≤5 years. * History of cancer with high risk of recurrence and preventing completion of the trial. * 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). * Have any clinically important abnormality at screening on magnetic resonance imaging (MRI) or clinical laboratory test results that could be detrimental to the participant or study integrity. * Have any contraindications for MRI, including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker. * Have a centrally read MRI demonstrating presence of amyloid-related imaging abnormalities (ARIA-E), \>4 cerebral microhemorrhages, more than 1 area of superficial siderosis, any macrohemorrhage or severe white matter disease at screening. * Have had prior treatment with a passive anti-amyloid immunotherapy \<5 half-lives prior to randomization. * Have received active immunization against amyloid beta (Aβ) in any other study. * Have received active immunization against Aβ in any other study. * Current or previous use of prescription medications used as treatment for mild cognitive impairment (MCI) or AD. Addendum 7
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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]) | Estimated up to Week 332 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Cognitive Composite in the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up to Week 332 | Change from baseline in Cognitive Composite in the Primary Study Population (CDR-GS 0) |
| Change from Baseline in International Shopping List Test (ISLT) in the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up to Week 332 | Change from baseline in clinical progression as measured by ISLT in the Primary Study Population (Baseline CDR-GS 0) |
| Change from Baseline in Continuous Paired Associate Learning (CPAL ) in the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up to Week 332 | Change from baseline in clinical progression as measured by CPAL in the Primary Study Population (baseline CDR-GS 0) |
| Change from Baseline in International Daily Symbol Substitution Test-Medicines (iDSSTm) in the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up to Week 332 | Change from baseline in clinical progression as measured by iDSSTm in the Primary Study Population (Baseline CDR-GS 0) |
| Change from Baseline in Category Fluency in the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up to Week 332 | Change from baseline in clinical progression as measured by Category Fluency in the Primary Study Population (Baseline CDR-GS 0) |
| Change from Baseline in CDR-Sum of Boxes (CDR-SB) n the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up Week 332 | Change from baseline in clinical progression as measured by CDR-SB in the Primary Study Population (Baseline CDR-GS 0) |
| Change from Baseline in Cognitive Function Index (CFI) in the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up to Week 332 | Change from baseline in clinical progression as measured by CFI in the Primary Study Population (Baseline CDR-GS 0) |
| Change from Baseline in Montreal Cognitive Assessment (MoCA) Score in the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up to Week 332 | Change from baseline in clinical progression as measured by MoCA score in the Primary Study Population (Baseline CDR-GS 0) |
| Change from Baseline in Mild Behavioral Impairment Checklist (MBI-C) in the Primary Study Population (Baseline CDR-GS 0) | Baseline, Up to Week 332 | Change from baseline in MBI-C in the Primary Study Population (Baseline CDR-GS 0) |
| Time to Clinical Progression of Composite Endpoint as Measured by CDR in the Overall Study Population (Baseline CDR-GS 0 or 0.5) | Baseline, Up to Week 332 | Time to clinical progression as measured by CDR in the Overall Study Population (Baseline CDR-GS 0 or 0.5) |
| Time to Clinical Progression as Measured by CDR Memory Box in Primary Study Population (Baseline CDR-GS 0) | Estimated up to Week 332 | Time to clinical progression as measured by CDR Memory 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) | 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 At Least 0.5 Change on CDR-SB in Primary Study Population (Baseline CDR-GS 0) | 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 of Composite Endpoint as Measured by CDR in Subpopulation Positive Based on Secondary Diagnostic Test | Estimated up to Week 332 | Time to clinical progression as measured by CDR in subpopulation positive based on secondary diagnostic test |
| Change from Baseline in Plasma P-tau217 | Baseline, Up to Week 332 | Change from baseline in Plasma P-tau217 |
| Pharmacokinetics (PK): Average Serum Donanemab Concentration at Steady State | Baseline through Week 76 | PK: Average serum donanemab concentration at steady state |
| Percentage of Participants with Treatment-emergent Anti-Drug Antibody (ADAs) | Baseline through Week 16 | Percentage of participants with treatment-emergent anti-drug antibody (ADAs) |
Countries
Japan, Puerto Rico, United States
Contacts
STUDY_DIRECTORCall 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
Outcome results
None listed