Recruiting
Phase 1

LY3954068

Sponsor:

Eli Lilly and Company

Code:

NCT06297590

Conditions

Alzheimer Disease

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Not accepted

Interventions

LY3954068

Placebo

Flortaucipir F18

Study Details

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.

Conditions

Alzheimer Disease

Study ID

NCT06297590

Start date

Aug 15, 2024

Status verified date

Aug, 2026

Completion date

Feb, 2027

Anticipated

Primary completion date

Feb, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 50 - 70+

Healthy Volunteers: Not 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.

Study Design

Enrollment

48 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: LY3954068 (Part A)

Single ascending dose of LY3954068 administered intrathecally (IT)

placebo comparator: Placebo (Part A)

Single ascending dose of placebo administered IT

experimental: LY3954068 (Part B)

Multiple ascending dose of LY3954068 administered IT

placebo comparator: Placebo (Part B)

Multiple ascending dose of placebo administered IT

Interventions

LY3954068

Administered IT

Placebo

Administered IT

Flortaucipir F18

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

Primary outcome measure

  • 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) ]
  • 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 ]

Central Contacts and Locations

Central contacts

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

1-317-615-4559LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

K2 Medical Research, LLC

Recruiting

Maitland, Florida, United States, 32751

Contacts

407-500-5252

Principal Investigator:

Brandon Lenox

Charter Research, LLC

Recruiting

The Villages, Florida, United States, 32162

Contacts

352-775-1000

Principal Investigator:

Jeffrey Norton

CenExel iResearch, LLC (CenExel iRA)

Recruiting

Decatur, Georgia, United States, 30030

Contacts

404-537-1281

Principal Investigator:

Kimball Johnson

CenExel AMRI

Recruiting

Toms River, New Jersey, United States, 08755

Contacts

732-341-9500

Principal Investigator:

Arun Singh

Duke University

Recruiting

Durham, North Carolina, United States, 27710

Contacts

919-684-5196

Principal Investigator:

Shruti Raja

More Information

Sponsor

Eli Lilly and Company

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Keywords

  • Dementia
  • Brain Diseases
  • Central Nervous System Diseases
  • Nervous System Diseases
  • Tauopathies
  • Tau
  • Neurodegenerative Diseases
  • Neurocognitive Disorders
  • Mental Disorders
  • Mild Cognitive Impairment

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-08-24.