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RECRUITINGPhase 1INTERVENTIONAL

A First-In-Human Study of LY3954068 in Participants With Early Symptomatic Alzheimer's Disease

A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3954068 in Patients With Early Symptomatic Alzheimer's Disease

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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. Who Should NOT Join This Trial: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

DRUG

LY3954068

Administered IT

DRUG

Placebo

Administered IT

DRUG

Flortaucipir F18

Administered intravenously (IV) prior to Positron Emission Tomography (PET) scan

Locations (10)

K2 Medical Research, LLC
Maitland, Florida, United States
Charter Research, LLC
The Villages, Florida, United States
CenExel iResearch, LLC (CenExel iRA)
Decatur, Georgia, United States
Massachusetts General Hospital (MGH)
Charlestown, Massachusetts, United States
CenExel AMRI
Toms River, New Jersey, United States
Duke University
Durham, North Carolina, United States
The University of Tokyo Hospital
Bunkyō City, Japan
National Hospital for Neurology and Neurosurgery (UCLH)
London, United Kingdom
Royal Hallamshire Hospital
Sheffield, United Kingdom
University Hospital Southampton
Southampton, United Kingdom