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NCT Number: NCT07787169

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

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).

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Key information

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Irvine Clinical Research, Irvine, California, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LY4405094

Drug

Administered intravenously (IV)

Placebo

Drug

Administered IV

Florbetapir F18

Other

Administered IV

Florbetaben F 18

Other

Administered IV

Primary outcomes

  1. The number of participants allocated to each substudy

    Time frame: Baseline up to Day 160

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

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

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Aug 26, 2026
Registry last updated
Aug 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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