RecruitingPhase 1

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

A Master Protocol for Phase 1 Clinical Trials of Multiple Amyloid-Targeting Therapies for the Treatment of Alzheimer's Disease

Lead sponsor

Eli Lilly and Company

Asset

LY4405094

Listed sites

Recruiting sites

Enrollment

179

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•MCI due to AD / mild-to-moderate AD / moderate AD dementia•Amyloid biomarker required (PET)•MMSE ≥16•Study partner/caregiver required•Healthy volunteers

Primary endpoint

•Number of participants allocated to each substudy

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Ctis2026-527295-81-00

Org study ID27909

Secondary IDA1D-MC-AT01Eli Lilly and Company

Secondary IDA1D-MC-AT02Eli Lilly and Company

Secondary IDA1D-MC-ATMPEli Lilly and Company

NCT IDNCT07787169

Timeline

Milestones

Study first posted2026-08-26actual

Study start2026-09-09actual

Last update posted2026-11-05actual

Primary completion2028-07estimated (month precision)

Study completion2028-07estimated (month precision)

Assets

Drug assets

LY4405094

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age18 Years

Maximum age85 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

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.

Endpoints (1)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Other (unclassified)

1 endpoint

Primary/protocol endpoint/low confidence

The number of participants allocated to each substudy

Time frame:Baseline up to Day 160

event count, event

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateNovember 5, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the November 5, 2026 snapshot.