Alzheimer Disease
Conditions
Keywords
Dementia, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Tau, Neurodegenerative Diseases, Neurocognitive Disorders, Mental Disorders, Mild Cognitive Impairment
Brief summary
The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD). The study will also investigate how much LY3954068 gets into the bloodstream and will test the effects of LY3954068 on markers of AD. The study will be comprised of two parts, A and B. Each enrolled participant in Part A will receive a single dose of LY3954068 or placebo (no active drug) given into the spinal fluid. Each participant in Part B will receive 2 doses of either LY3954068 or placebo administered into the spinal fluid. Participants will have the opportunity to join an optional bridging period to a separate potential study where participants would receive LY3954068. The study will last up to approximately 45 weeks for Part A, and 100 weeks for Part B, including the screening period.
Interventions
DRUGLY3954068
Administered IT
DRUGPlacebo
Administered IT
DRUGFlortaucipir F18
Administered intravenously (IV) prior to Positron Emission Tomography (PET) scan
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Have a body mass index (BMI) within the range 18 to 40 kilograms per square meter (kg/m²), inclusive, at screening. * Have gradual and progressive change in memory function for greater than or equal to (≥) 6 months as reported by the participant or informant. * Have a mini mental state examination (MMSE) score of 18 to 30 at screening. * Have a clinical dementia rating (CDR) global score of 0.5 to 1.0, with a memory box score ≥ 0.5 at screening. * Meet flortaucipir F18 positron emission tomography (PET) criteria, as defined in the TAUVID™ FDA label (TAUVID™ prescribing information, 2024), demonstrating evidence of tau pathology. * Males who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP). * Participants must have up to 2 study partners who are with contact with the participant at least 10 hours per week and one of whom can attend study appointments.
Exclusion criteria
* Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (other than Alzheimer's Disease), psychiatric, immunologic, 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 less than (\<)24 months. * Have a sensitivity to flortaucipir F18. * Have contraindication to magnetic resonance imaging (MRI), including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker. * Have a current exposure to an amyloid targeted therapy (ATT). Prior exposure to ATTs greater than 1 year from the last dose may be permitted at the discretion of the investigator and in consultation with the sponsor. * Have previous exposure to any Investigational Medicinal Product administered intrathecal (IT) or previous exposure to any anti-tau therapy. * Have a history of clinically significant back pain, back pathology and/or back injury (for example, degenerative disease, spinal deformity or spinal surgery) that may predispose to complications or technical difficulty with lumbar puncture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration | Baseline up to Week 24 and Week 72 (for optional bridging period participants) | A summary of AEs, TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module |
| Part B: Number of participants with one or more Adverse Event (s) (AEs), Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration | Baseline up to Week 52 | A summary of AEs, TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) | Day 1 up to Week 24 | To evaluate plasma concentration of LY3954068 |
| Part B: PK: Cmax | Day -1 up to Week 52 | To evaluate plasma concentration of LY3954068 |
| Part A: PK: Area Under the Concentration Versus Time Curve (AUC) | Day 1 up to Week 24 | To evaluate plasma concentration of LY3954068 |
| Part B: PK: AUC | Day -1 up to Week 52 | To evaluate plasma concentration of LY3954068 |
| Part A: PK: Cerebrospinal Fluid (CSF) concentration of LY3954068 | Day 3 up to Week 24 | To evaluate CSF concentration of LY3954068 |
| Part B: PK: CSF concentration of LY3954068 | Day 3 up to Week 52 | To evaluate CSF concentration of LY3954068 |
| Part A: Pharmacodynamics (PD): Change from Baseline of CSF tau | Baseline up to Week 24 | To evaluate the effect of LY3954068 on CSF tau |
| Part B: PD: Change from Baseline of CSF tau | Baseline up to Week 52 | To evaluate the effect of LY3954068 on CSF tau |
Countries
Japan, United Kingdom, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed