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

NCT07787169 | Not Yet Recruiting Phase 1 FDA Drug

• 4 other identifiers: 279092026-527295-81-00A1D-MC-ATMPA1D-MC-AT01
• Study Type: interventional
• Target: 179
• Locations: 1 country
• Sites: 10

Brief 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).

Conditions

Alzheimer Disease; Plaque, Amyloid; Healthy Volunteers; Amyloid

Outcome Measures

Primary Outcomes (1)

• The number of participants allocated to each substudy

  Baseline up to Day 160

Study Arms (2)

LY4405094 Study AT01 (Healthy ISA)

EXPERIMENTAL

LY4405094 or placebo administered intravenously (IV) or subcutaneously (SC) in healthy volunteers.

Drug: LY4405094; Drug: Placebo

LY4405094 Study AT01 (AD ISA)

EXPERIMENTAL

LY4405094 or placebo administered IV to participants with AD. Florbetapir F 18 or Florbetaben F 18 will be administered IV during amyloid positron emission tomography (PET) scan.

Drug: LY4405094; Drug: Placebo; Other: Florbetapir F18; Other: Florbetaben F 18

Interventions

LY4405094 DRUG

Administered intravenously (IV)

LY4405094 Study AT01 (AD ISA); LY4405094 Study AT01 (Healthy ISA)

Placebo DRUG

Administered IV

LY4405094 Study AT01 (AD ISA); LY4405094 Study AT01 (Healthy ISA)

Florbetapir F18 OTHER

Administered IV

LY4405094 Study AT01 (AD ISA)

Florbetaben F 18 OTHER

Administered IV

LY4405094 Study AT01 (AD ISA)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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).
• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (10)

Irvine Clinical Research

Irvine, California, 92614, United States

Location

Fortrea Clinical Research Unit

Daytona Beach, Florida, 32117, United States

Location

K2 Medical Research - The Villages

Lady Lake, Florida, 32159, United States

Location

K2 Medical Research

Maitland, Florida, 32751, United States

Location

Charter Research

Orlando, Florida, 32803, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

K2 Medical Research - Tampa

Tampa, Florida, 33634, United States

Location

Charter Research

The Villages, Florida, 32162-2698, United States

Location

Accel Research Sites - NeuroStudies Clinical Research Unit

Decatur, Georgia, 30030, United States

Location

QUEST Research Institute

Farmington Hills, Michigan, 48334, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Plaque, Amyloid

Interventions

florbetapir; 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2026
• First Posted: August 26, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: August 27, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)