A Master Protocol Studying Multiple Amyloid-Targeting Therapies in Healthy Participants and Participants With Alzheimer's Disease

Summary

The purpose of this Master Protocol is to support multiple studies looking at safety and tolerability of different drugs in healthy participants and participants with Alzheimer's disease, and if they remove clumps of protein (amyloid plaque) in the brain in participants with Alzheimer's Disease. Participants will enroll into either A1D-MC-AT01 (NCT07787182) or A1D-MC-AT02 (upcoming).

Interventions

• LY4405094 · DRUG

  Administered intravenously (IV)

• LY4405094 · DRUG

  Administered Subcutaneously (SC)

• Placebo · DRUG

  Administered IV

• Placebo · DRUG

  Administered SC

• Florbetapir F18 · OTHER

  Administered IV

• Florbetaben F 18 · OTHER

  Administered IV

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Participants must meet eligibility criteria below. Additional criteria are specified in the substudy to which the participant will enroll.

Inclusion Criteria for Healthy Participants:

* Are between 18 and 45 years of age
* Have a body mass index (BMI) of 18.0 to 32.0 kilograms per square meter (kg/m²)
* Are overtly healthy as determined by medical evaluation, including medical history, physical examination, and electrocardiograms (ECGs).

Inclusion Criteria for Participants with Alzheimer's Disease (AD):

* Are between 55-85 years of age
* Have gradual and progressive changes in memory function, as reported by the participant or their study partner, for greater than or equal to (≥) 6 months at screening, as well as a clinical diagnosis of mild cognitive impairment due to AD or mild-to-moderate AD dementia as determined by the investigator or based on medical history.
* Have Mini-Mental State Exam (MMSE) score ≥16
* Have positive amyloid positron emission tomography (PET)
* Have a reliable study partner who will provide written informed consent to participate and is in frequent contact with the participant. A second person may serve as backup.
* For participants on symptomatic treatments for AD (for example, cholinesterase inhibitors, memantine) the dosing regimen must be stable, in the opinion of the investigator, for at least 8 weeks before randomization to a study intervention, and the dosing regimen is planned to remain stable.

Exclusion Criteria for all Participants:

* Have currently, or a history of, serious or unstable neurological or psychological disease (except for AD for participants in the AD cohorts).
* Have currently, or a history of, significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological diseases.
* Have currently, or a history of, allergies to monoclonal antibodies, diphenhydramine, epinephrine, or methylprednisolone.
* Have currently, or a history of, clinically significant multiple or severe drug allergies or severe posttreatment hypersensitivity reactions.
* Have currently, or a history of cancer within the past 5 years except for some early skin cancers that have been resected with no evidence of metastatic disease for 3 years.
* Have received any amyloid-targeting therapy (ATT), whether marketed or investigational; or have received active immunization against amyloid beta (Aβ).
* Have received an active study intervention, within the last 30 days, in a clinical study involving an IMP.
* Are pregnant or breastfeeding or intend to become pregnant or to breastfeed during the study;
* Have an abnormal blood pressure, pulse rate, or both, as determined by the investigator, or a preexisting history of hypertension.

Exclusion Criteria for Healthy Participants:

* Have a locally read brain magnetic resonance imaging (MRI) that demonstrates any clinically significant findings, including but not limited to, findings suggestive of CAA, that, in the opinion of the investigator, may impact the participant's ability to safely participate in the study.
* Have a history of clinically significant back pain, pathological conditions of the back, or back injury (for example, degenerative disease, spinal deformity, or spinal surgery), or have a local infection at the intended site of the lumbar puncture (LP) that may predispose to complications or technical difficulty with LP.
* Have a family history of early onset AD (AD diagnosed before 65 years of age).

Exclusion Criteria for Participants with AD:

* Contraindications or unable to tolerate MRI
* Have a centrally read brain MRI that demonstrates the presence of Amyloid-Related Imaging Abnormalities with Edema/Effusion (ARIA-E), greater than (\>)4 cerebral microhemorrhages, any evidence of superficial siderosis, any macrohemorrhage, or severe white matter disease; \>2 lacunar infarcts or any territorial infarct \>1 square centimeters (cm²); significant abnormalities that suggest another potential etiology for progressive dementia, or clinically significant finding that, in the opinion of the investigator, may impact the participant's ability to safely participate in the study.
* Contraindications to amyloid PET scan.

Sites (16)

• CenExel ACT, Anaheim, California
• Irvine Clinical Research, Irvine, California
• Collaborative Neuroscience Network - CNS, Los Alamitos, California
• Fortrea Clinical Research Unit, Daytona Beach, Florida
• K2 Medical Research - The Villages, Lady Lake, Florida
• K2 Medical Research, Maitland, Florida
• Charter Research, Orlando, Florida
• Progressive Medical Research, Port Orange, Florida
• Alzheimer's Research and Treatment Center, Stuart, Florida
• K2 Medical Research - Tampa, Tampa, Florida
• Charter Research, The Villages, Florida
• Accel Research Sites - NeuroStudies Clinical Research Unit, Decatur, Georgia
• QUEST Research Institute, Farmington Hills, Michigan
• Xuanwu Hospital Capital Medical University, Beijing, China
• The University of Tokyo Hospital, Bunkyō City, Japan
• National Center for Geriatrics and Gerontology, Ōbu, Japan