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

NCT06297590 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: 18795J4T-MC-OLAA2024-510604-37-00U1111-1302-6222
• Study Type: interventional
• Target: 48
• Locations: 3 countries
• Sites: 10

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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

  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

  Baseline up to Week 52

Secondary Outcomes (8)

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

  Day 1 up to Week 24

• Part B: PK: Cmax

  Day -1 up to Week 52

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

  Day 1 up to Week 24

• Part B: PK: AUC

  Day -1 up to Week 52

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

  Day 3 up to Week 24

Study Arms (4)

LY3954068 (Part A)

EXPERIMENTAL

Single ascending dose of LY3954068 administered intrathecally (IT)

Drug: LY3954068; Drug: Flortaucipir F18

Placebo (Part A)

PLACEBO COMPARATOR

Single ascending dose of placebo administered IT

Drug: Placebo; Drug: Flortaucipir F18

LY3954068 (Part B)

EXPERIMENTAL

Multiple ascending dose of LY3954068 administered IT

Drug: LY3954068; Drug: Flortaucipir F18

Placebo (Part B)

PLACEBO COMPARATOR

Multiple ascending dose of placebo administered IT

Drug: Placebo; Drug: Flortaucipir F18

Interventions

LY3954068 DRUG

Administered IT

LY3954068 (Part A); LY3954068 (Part B)

Placebo DRUG

Administered IT

Placebo (Part A); Placebo (Part B)

Flortaucipir F18 DRUG

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

LY3954068 (Part A); LY3954068 (Part B); Placebo (Part A); Placebo (Part B)

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (10)

K2 Medical Research, LLC

Maitland, Florida, 32751, United States

RECRUITING

Charter Research, LLC

The Villages, Florida, 32162, United States

RECRUITING

CenExel iResearch, LLC (CenExel iRA)

Decatur, Georgia, 30030, United States

RECRUITING

Massachusetts General Hospital (MGH)

Charlestown, Massachusetts, 02129, United States

NOT YET RECRUITING

CenExel AMRI

Toms River, New Jersey, 08755, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

The University of Tokyo Hospital

Bunkyō City, 113-8655, Japan

RECRUITING

National Hospital for Neurology and Neurosurgery (UCLH)

London, WC1N 3BG, United Kingdom

RECRUITING

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

NOT YET RECRUITING

University Hospital Southampton

Southampton, SO16 6YD, United Kingdom

NOT YET RECRUITING

Related Links

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

MeSH Terms

Conditions

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Pick Disease of the Brain; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognitive Dysfunction

Interventions

7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Condition Hierarchy (Ancestors)

Frontotemporal Dementia; Frontotemporal Lobar Degeneration; Cognition Disorders

Study Officials

• Call 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

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

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

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 7, 2024
• Study Start: August 15, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1); US (6); GB (3)