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NCT Number: NCT06297590

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

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.

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Key information

Conditions

Alzheimer Disease Brain Diseases Central Nervous System Diseases Cognition Disorders Cognitive Dysfunction Dementia Frontotemporal Dementia Frontotemporal Lobar Degeneration Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Pick Disease of the Brain Tauopathies

Age range

50 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

The University of Tokyo Hospital, Bunkyō City, Japan

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LY3954068

Drug

Administered IT

Placebo

Drug

Administered IT

Flortaucipir F18

Drug

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

Primary outcomes

  1. 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

    Time frame: 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

  2. 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

    Time frame: 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 outcomes

  1. Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)

    Time frame: Day 1 up to Week 24

    To evaluate plasma concentration of LY3954068

  2. Part B: PK: Cmax

    Time frame: Day -1 up to Week 52

    To evaluate plasma concentration of LY3954068

  3. Part A: PK: Area Under the Concentration Versus Time Curve (AUC)

    Time frame: Day 1 up to Week 24

    To evaluate plasma concentration of LY3954068

  4. Part B: PK: AUC

    Time frame: Day -1 up to Week 52

    To evaluate plasma concentration of LY3954068

  5. Part A: PK: Cerebrospinal Fluid (CSF) concentration of LY3954068

    Time frame: Day 3 up to Week 24

    To evaluate CSF concentration of LY3954068

  6. Part B: PK: CSF concentration of LY3954068

    Time frame: Day 3 up to Week 52

    To evaluate CSF concentration of LY3954068

  7. Part A: Pharmacodynamics (PD): Change from Baseline of CSF tau

    Time frame: Baseline up to Week 24

    To evaluate the effect of LY3954068 on CSF tau

  8. Part B: PD: Change from Baseline of CSF tau

    Time frame: Baseline up to Week 52

    To evaluate the effect of LY3954068 on CSF tau

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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 dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Mar 7, 2024
Registry last updated
Apr 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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