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

JRCT ID: jRCT2051240006

Registered date:03/04/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Alzheimer Disease
• Date of first enrollment: 30/06/2024
• Target sample size: 60
• Countries of recruitment: United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

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

[Study Arms]
Experimental: LY3954068 (Part A)
Single ascending dose of LY3954068 administered intrathecally (IT)
Interventions:
Drug: LY3954068
Drug: Flortaucipir F18
Placebo Comparator: Placebo (Part A)
Single ascending dose of placebo administered IT
Interventions:
Drug: Placebo
Drug: Flortaucipir F18
Experimental: LY3954068 (Optional Part B)
Multiple ascending dose of LY3954068 administered IT
Interventions:
Drug: LY3954068
Drug: Flortaucipir F18
Placebo Comparator: Placebo (Optional Part B)
Multiple ascending dose of placebo administered IT
Interventions:
Drug: Placebo
Drug: Flortaucipir F18

Outcome(s)

Primary Outcome

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 48 and Week 96 (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
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

Key inclusion & exclusion criteria

• Age minimum: >= 50age old
• Age maximum: <= 85age old
• Gender: Both

Include 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.

Exclude 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 Information

• Primary Sponsor: Wakayama Naohiko
• Secondary ID(s): NCT06297590