Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss

NCT ID: NCT02008357

Last Updated: 2023-12-28

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1169 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-28

Study Completion Date

2023-06-08

Brief Summary

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The purpose of this study is to test whether an investigational drug called solanezumab can slow the progression of memory problems associated with brain amyloid (protein that forms plaques in the brains of people with Alzheimer Disease \[AD\]).

Detailed Description

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The A4 study is a clinical trial for older individuals who have evidence of amyloid plaque build-up in their brains who may be at risk for memory loss and cognitive decline due to Alzheimer's disease. The A4 study will test an anti-amyloid investigational drug in older individuals who do not yet show symptoms of Alzheimer's disease cognitive impairment or dementia with the aim of slowing memory and cognitive decline. The A4 study will also test whether anti-amyloid treatment can delay the progression of AD related brain injury on imaging and other biomarkers.

Conditions

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Cognition Disorders

Keywords

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Cognition Prevention

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Solanezumab/Solanezumab

Participants received 400 milligram (mg) solanezumab followed by 800 mg solanezumab and then 1600 milligram solanezumab administered intravenously (IV) every 4 weeks (Q4W) for approximately 240 weeks in double-blind placebo-controlled period.

Participants begin open label extension and received 1600 mg solanezumab Q4W for 204 weeks (from week 240 to week 444).

Group Type EXPERIMENTAL

Solanezumab

Intervention Type DRUG

Administered IV

Placebo/Solanezumab

Participants received placebo administered IV Q4W for approximately 240 weeks in double-blind period.

Participants begin open label extension period and received 1600 mg solanezumab Q4W for 204 weeks (from week 240 to week 444).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Administered IV

Solanezumab

Intervention Type DRUG

Administered IV

Interventions

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Placebo

Administered IV

Intervention Type DRUG

Solanezumab

Administered IV

Intervention Type DRUG

Other Intervention Names

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LY2062430

Eligibility Criteria

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Inclusion Criteria

* Has a Mini-Mental State Examination (MMSE) score at screening of 25 to 30
* Has a global Clinical Dementia Rating (CDR) scale score at screening of 0
* Has a Logical Memory II score at screening of 6 to 18
* Has a florbetapir positron emission tomography (PET) scan that shows evidence of brain amyloid pathology at screening
* Has a study partner that is willing to participate as a source of information and has at least weekly contact with the participant (contact can be in-person, via telephone or electronic communication)


* All participants who complete the placebo-controlled period will be allowed to continue into the open-label period

Exclusion Criteria

* Is receiving a prescription acetylcholinesterase inhibitor (AChEI) and/or memantine at screening or baseline
* Lacks good venous access, such that intravenous drug delivery or multiple blood draws would be precluded
* Has current serious or unstable illness including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study
* Has had a history within the last 5 years of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis) or head trauma resulting in protracted loss of consciousness
* Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of any in situ cancer that was appropriately treated and is being appropriately monitored, such as resected cutaneous squamous cell carcinoma in situ or in situ prostate cancer with normal prostate-specific antigen post-treatment
* Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis)
* Is clinically judged by the investigator to be at serious risk for suicide
* Has a history within the past 2 years of major depression or bipolar disorder as defined by the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM)
* Has a history within the past 5 years of chronic alcohol or drug abuse/dependence as defined by the most current version of the DSM
Minimum Eligible Age

65 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alzheimer's Therapeutic Research Institute

OTHER

Sponsor Role collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner Health Research Institute

Phoenix, Arizona, United States

Site Status

Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

Banner Sun Health Research Institute

Sun City, Arizona, United States

Site Status

Institute for Memory Impairment & Neurological Disorders

Irvine, California, United States

Site Status

University of California - San Diego

La Jolla, California, United States

Site Status

University of Southern California School of Medicine

Los Angeles, California, United States

Site Status

University of California - Los Angeles

Los Angeles, California, United States

Site Status

Univ of California Irvine College of Medicine

Orange, California, United States

Site Status

Veterans Affairs Medical Center Palo Alto

Palo Alto, California, United States

Site Status

Sutter Medical Group

Sacramento, California, United States

Site Status

Univ of California San Francisco

San Francisco, California, United States

Site Status

Syrentis Clinical Research

Santa Ana, California, United States

Site Status

University of California, Davis - Health Systems

Walnut Creek, California, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Howard University Hospital

Washington D.C., District of Columbia, United States

Site Status

Brain Matters Research

Delray Beach, Florida, United States

Site Status

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States

Site Status

Wien Center for Clinical Research

Miami Beach, Florida, United States

Site Status

Compass Research - Orlando

Orlando, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Compass Research -The Villages

The Villages, Florida, United States

Site Status

Premiere Research Institute at Palm Beach Neurology

West Palm Beach, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush Alzheimer's Disease Center

Chicago, Illinois, United States

Site Status

Great Lakes Clinical Trials

Chicago, Illinois, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas Hospital

Fairway, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

Site Status

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status

Brigham and Womens Hospital

Boston, Massachusetts, United States

Site Status

Boston University Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Univ of Nebraska Med Center

Omaha, Nebraska, United States

Site Status

Cleveland Clinic of Las Vegas

Las Vegas, Nevada, United States

Site Status

Dent Neurological Institute

Amherst, New York, United States

Site Status

New York University Medical Center

New York, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States

Site Status

Case Western Reserve University

Beachwood, Ohio, United States

Site Status

Tulsa Clinical Research LLC

Tulsa, Oklahoma, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Drexel University College of Medicine at EPPI

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Butler Hospital

Providence, Rhode Island, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Roper Hospital

Charleston, South Carolina, United States

Site Status

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Houston Methodist

Houston, Texas, United States

Site Status

University of Washington School of Medicine

Seattle, Washington, United States

Site Status

University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, United States

Site Status

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Parkville, Victoria, Australia

Site Status

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

London, , Canada

Site Status

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

Toronto, , Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, , Canada

Site Status

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

Vancouver, , Canada

Site Status

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Bunkyō City, , Japan

Site Status

Countries

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United States Australia Canada Japan

References

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Shirzadi Z, Schultz AP, Loghmani N, Yang HS, Ford J, Yaari R, Properzi M, Yau WW, Liu L, Rafii MS, Donohue MC, Brickman AM, Jack CR Jr, Greenberg SM, Aisen P, Sperling RA, Chhatwal JP; A4 Study Team. Independent effects of white matter lesion volume and APOE varepsilon4 on ARIA-H in A4 Study. Alzheimers Dement. 2025 Oct;21(10):e70751. doi: 10.1002/alz.70751.

Reference Type DERIVED
PMID: 41085172 (View on PubMed)

Digma LA, Young CB, Winer JR, Cody KA, Younes K, Sheng J, Insel PS, Rissman RA, Sperling R, Mormino EC. Continuum of Core 1 Biomarkers in Preclinical Alzheimer's Disease. medRxiv [Preprint]. 2025 Sep 19:2025.09.17.25336007. doi: 10.1101/2025.09.17.25336007.

Reference Type DERIVED
PMID: 41001450 (View on PubMed)

Farina FR, Bennett M, Grill JD, Sperling R, Lawlor B, Griffith JW. Association of Alzheimer's disease concerns with amyloid burden and lifestyle behaviors in cognitively unimpaired older adults. Alzheimers Dement. 2025 Jun;21(6):e70225. doi: 10.1002/alz.70225.

Reference Type DERIVED
PMID: 40476544 (View on PubMed)

Dubbelman MA, Liu A, Donohue MC, Langford O, Raman R, Rentz DM, Amariglio R, Sperling RA, Aisen PS, Marshall GA; as the A4 Study team. Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid. Neurology. 2025 Jun 24;104(12):e213775. doi: 10.1212/WNL.0000000000213775. Epub 2025 May 29.

Reference Type DERIVED
PMID: 40440591 (View on PubMed)

Sperling RA, Donohue MC, Raman R, Rafii MS, Johnson K, Masters CL, van Dyck CH, Iwatsubo T, Marshall GA, Yaari R, Mancini M, Holdridge KC, Case M, Sims JR, Aisen PS; A4 Study Team. Trial of Solanezumab in Preclinical Alzheimer's Disease. N Engl J Med. 2023 Sep 21;389(12):1096-1107. doi: 10.1056/NEJMoa2305032. Epub 2023 Jul 17.

Reference Type DERIVED
PMID: 37458272 (View on PubMed)

Lewis CK, Bernstein OM, Grill JD, Gillen DL, Sultzer DL. Anxiety and Depressive Symptoms and Cortical Amyloid-beta Burden in Cognitively Unimpaired Older Adults. J Prev Alzheimers Dis. 2022;9(2):286-296. doi: 10.14283/jpad.2022.13.

Reference Type DERIVED
PMID: 35543002 (View on PubMed)

Grober E, Lipton RB, Sperling RA, Papp KV, Johnson KA, Rentz DM, Veroff AE, Aisen PS, Ezzati A. Associations of Stages of Objective Memory Impairment With Amyloid PET and Structural MRI: The A4 Study. Neurology. 2022 Mar 29;98(13):e1327-e1336. doi: 10.1212/WNL.0000000000200046. Epub 2022 Feb 23.

Reference Type DERIVED
PMID: 35197359 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://trials.lillytrialguide.com/en-US/trial/4qngyPbBRKqiYWCI0ouGIQ

A Study of Solanezumab in Older Participants Who May be at Risk for Memory Loss (A4)

Other Identifiers

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H8A-MC-LZAZ

Identifier Type: OTHER

Identifier Source: secondary_id

15275

Identifier Type: -

Identifier Source: org_study_id