RecruitingPhase 1

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

Lead sponsor

Eli Lilly and Company

Asset

LY3954068

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•Tau biomarker required (PET)•CDR global 0.5-1•MMSE 18-30•MRI contraindications excluded

Primary endpoints

•Part•Part B

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID18795

Secondary ID2024-510604-37-00EU Trial Number

Secondary IDJ4T-MC-OLAAEli Lilly and Company

NCT IDNCT06297590

Secondary IDU1111-1302-6222Universal Trial Number

Timeline

Milestones

Study first posted2024-03-07actual

Study start2024-08-15actual

Last update posted2026-04-20actual

Primary completion2027-02estimated (month precision)

Study completion2027-02estimated (month precision)

Assets

Drug assets

LY3954068

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (10)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Fluid / digital biomarkers

4 endpoints

Secondary/protocol endpoint

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

Time frame:Day 3 up to Week 24

concentration, descriptive

Secondary/protocol endpoint

Part B: PK: CSF concentration of LY3954068

Time frame:Day 3 up to Week 52

concentration, descriptive

Secondary/protocol endpoint

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

Time frame:Baseline up to Week 24

change from baseline, improvement

Secondary/protocol endpoint

Part B: PD: Change from Baseline of CSF tau

Time frame:Baseline up to Week 52

change from baseline, improvement

Safety / tolerability / PK

6 endpoints

Primary/protocol endpoint

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)

event count, event

Primary/protocol endpoint

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

event count, event

Secondary/protocol endpoint

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

Time frame:Day 1 up to Week 24

concentration, descriptive

Secondary/protocol endpoint

Part B: PK: Cmax

Time frame:Day -1 up to Week 52

concentration, descriptive

Secondary/protocol endpoint

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

Time frame:Day 1 up to Week 24

concentration, descriptive

Secondary/protocol endpoint

Part B: PK: AUC

Time frame:Day -1 up to Week 52

concentration, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.