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

Alzheimer Disease Clinical Trial

Official 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06297590
• Other study ID #: 18795
• Secondary ID: J4T-MC-OLAA2024-
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: February 2027

Study information

• Verified date: April 2024
• Source: Eli Lilly and Company
• Contact: There may be multiple sites in this clinical trial. 1-877-CTLILL
• Phone: 1-317-615-4559
• Email: ClinicalTrials.gov[@]Lilly.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. Part B is optional, and participants from Part A may also have the opportunity to join an optional bridging period to a separate potential study where participants would receive LY3954068. Each enrolled participant in Part A will receive a single dose of LY3954068 or placebo (no active drug) given into the spinal fluid. If conducted, each participant in Part B would receive 2 doses of either LY3954068 or placebo administered into the spinal fluid.

The study will last up to approximately 69 weeks for Part A, and, if conducted, 73 weeks for Part B. If conducted, the optional bridging period for Part A participants would last up to approximately 1 year after their completion of Part A.

If the optional bridging period is conducted, participants in Part A could be enrolled in the separate potential study for up to approximately 120 weeks.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: February 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• Have a body mass index (BMI) within the range 18 (17 for Japan participants) 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 positron emission tomography (PET) criteria 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 18F.

• 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 sponsor and in consultation with the sponsor.

• Have previous exposure to any Investigational Medicinal Product administered 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.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• LY3954068
Administered IT
• Placebo
Administered IT
• Flortaucipir F18
Administered intravenously (IV) prior to Positron Emission Tomography (PET) scan

Locations

Country	Name	City	State
Japan	The University of Tokyo Hospital	Bunkyo-ku	Tokyo
United Kingdom	National Hospital for Neurology and Neurosurgery (UCLH)	London
United Kingdom	Royal Hallamshire Hospital	Sheffield
United Kingdom	University Hospital Southampton	Southampton
United States	Massachusetts General Hospital (MGH)	Charlestown	Massachusetts
United States	Duke University	Durham	North Carolina
United States	Indiana University School of Medicine - Clinical Research Center	Indianapolis	Indiana
United States	K2 Medical Research LLC	Maitland	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Charter Research, LLC	The Villages	Florida
United States	CenExel AMRI	Toms River	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 48 and Week 96 (for optional bridging period participants)
Primary	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	Part A: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)	To evaluate plasma concentration of LY3954068	Day 1 up to Week 48
Secondary	Optional Part B: PK: Cmax	To evaluate plasma concentration of LY3954068	Day -1 up to Week 52
Secondary	Part A: PK: Area Under the Concentration Versus Time Curve (AUC)	To evaluate plasma concentration of LY3954068	Day 1 up to Week 48
Secondary	Optional Part B: PK: AUC	To evaluate plasma concentration of LY3954068	Day -1 up to Week 52
Secondary	Part A: PK: Cerebrospinal Fluid (CSF) concentration of LY3954068	To evaluate CSF concentration of LY3954068	Day 1 up to Week 48
Secondary	Optional Part B: PK: CSF concentration of LY3954068	To evaluate CSF concentration of LY3954068	Day -1 up to Week 52
Secondary	Part A: Pharmacodynamics (PD): Change from Baseline of CSF tau	To evaluate the effect of LY3954068 on CSF tau	Baseline up to Week 48
Secondary	Optional Part B: PD: Change from Baseline of CSF tau	To evaluate the effect of LY3954068 on CSF tau	Baseline up to Week 52

External Links

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