Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss (A4)

• ClinicalTrials.gov Identifier: NCT02008357
• Recruitment Status: Active, not recruiting
• First Posted: December 11, 2013
• Last Update Posted: January 18, 2023
• Sponsor: Eli Lilly and Company
• Collaborator: Alzheimer's Therapeutic Research Institute
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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]).

Condition or disease	Intervention/treatment	Phase
Cognition Disorders	Drug: Placebo; Drug: Solanezumab	Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)
• Actual Study Start Date: February 28, 2014
• Actual Primary Completion Date: December 27, 2022
• Estimated Study Completion Date: June 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Solanezumab; Solanezumab (400-1600 milligrams) intravenously (IV) every 4 weeks for 240 weeks. Participants who enter the open-label extension will receive solanezumab IV.	Drug: Solanezumab; Administered IV; Other Name: LY2062430
Placebo Comparator: Placebo; Placebo IV every 4 weeks for 240 weeks. Participants who enter the open-label extension will receive solanezumab IV.	Drug: Placebo; Administered IV; Drug: Solanezumab; Administered IV; Other Name: LY2062430

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) [ Time Frame: Baseline, Week 240; Baseline, Week 336 ]

Secondary Outcome Measures :

1. Change from Baseline in Cognitive Function Index (CFI) [ Time Frame: Baseline, Week 240; Baseline, Week 336 ]
2. Change from Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Questionnaire (ADCS-ADL-Prevention Questionnaire) Score [ Time Frame: Baseline, Week 240; Baseline, Week 336 ]
3. Change from Baseline in Mean Composite Standardized Uptake Value Ratio (SUVr) [ Time Frame: Baseline, Week 240 ]
4. Change from Baseline in Cerebrospinal Fluid (CSF) Tau Biomarkers [ Time Frame: Baseline, Week 240 ]
5. Change from Baseline of CSF Concentrations of Amyloid Beta (Abeta) [ Time Frame: Baseline, Week 240 ]
6. Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline, Week 240 ]
7. Change from Baseline on the Clinical Dementia Rating-Sum of Boxes score (CDR-SB) [ Time Frame: Baseline, Week 336 ]
8. Change from Baseline on the Computerized Cognitive Composite (C3) [ Time Frame: Baseline, Week 336 ]

Eligibility Criteria

• Ages Eligible for Study: 65 Years to 85 Years (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

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

Open-Label Inclusion Criteria:

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, Arizona

Banner Health Research Institute

Phoenix, Arizona, United States, 85006

Barrow Neurological Institute

Phoenix, Arizona, United States, 85013

Banner Sun Health Research Institute

Sun City, Arizona, United States, 85351

United States, California

Institute for Memory Impairment & Neurological Disorders

Irvine, California, United States, 92697

University of California - San Diego

La Jolla, California, United States, 92037

University of Southern California School of Medicine

Los Angeles, California, United States, 90033

University of California - Los Angeles

Los Angeles, California, United States, 90095

Univ of California Irvine College of Medicine

Orange, California, United States, 92868

Veterans Affairs Medical Center Palo Alto

Palo Alto, California, United States, 94304

Sutter Medical Group

Sacramento, California, United States, 95816

Univ of California San Francisco

San Francisco, California, United States, 94158

Syrentis Clinical Research

Santa Ana, California, United States, 92705

University of California, Davis - Health Systems

Walnut Creek, California, United States, 94598

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06510

United States, District of Columbia

Georgetown University Hospital

Washington, District of Columbia, United States, 20057

Howard University Hospital

Washington, District of Columbia, United States, 20060

United States, Florida

Brain Matters Research

Delray Beach, Florida, United States, 33445

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States, 32224

Wien Center for Clinical Research

Miami Beach, Florida, United States, 33140

Compass Research - Orlando

Orlando, Florida, United States, 32806

University of South Florida

Tampa, Florida, United States, 33613

Compass Research -The Villages

The Villages, Florida, United States, 32162

Premiere Research Institute at Palm Beach Neurology

West Palm Beach, Florida, United States, 33407

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

Rush Alzheimer's Disease Center

Chicago, Illinois, United States, 60612

Great Lakes Clinical Trials

Chicago, Illinois, United States, 60640

United States, Indiana

Indiana University School of Medicine

Indianapolis, Indiana, United States, 46202

United States, Iowa

University of Iowa

Iowa City, Iowa, United States, 52242

United States, Kansas

University of Kansas Hospital

Fairway, Kansas, United States, 66205

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40504

United States, Louisiana

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States, 70808-4124

United States, Maryland

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States, 21093

United States, Massachusetts

Brigham and Womens Hospital

Boston, Massachusetts, United States, 02115

Boston University Medical Center

Boston, Massachusetts, United States, 02118

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48105

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, Nebraska

Univ of Nebraska Med Center

Omaha, Nebraska, United States, 68198

United States, Nevada

Cleveland Clinic of Las Vegas

Las Vegas, Nevada, United States, 89106

United States, New York

Dent Neurological Institute

Amherst, New York, United States, 14226

New York University Medical Center

New York, New York, United States, 10016

Weill Cornell Medical College

New York, New York, United States, 10021

Mount Sinai School of Medicine

New York, New York, United States, 10029

Columbia University Medical Center

New York, New York, United States, 10032

University of Rochester

Rochester, New York, United States, 14620

United States, North Carolina

Wake Forest University School of Medicine

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Case Western Reserve University

Beachwood, Ohio, United States, 44122

United States, Oklahoma

Tulsa Clinical Research LLC

Tulsa, Oklahoma, United States, 74104

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Drexel University College of Medicine at EPPI

Philadelphia, Pennsylvania, United States, 19102

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, Rhode Island

Butler Hospital

Providence, Rhode Island, United States, 02906

Rhode Island Hospital

Providence, Rhode Island, United States, 02906

United States, South Carolina

Roper Hospital

Charleston, South Carolina, United States, 29401

United States, Texas

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States, 75235

Baylor College of Medicine

Houston, Texas, United States, 77030

Houston Methodist

Houston, Texas, United States, 77030

United States, Washington

University of Washington School of Medicine

Seattle, Washington, United States, 98108

United States, Wisconsin

University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, United States, 53705

Australia, Victoria

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, 3010

Canada

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, N6C 0A7

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, M3B2S7

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, M4N 3M5

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, V6T 2B5

Japan

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.

Bunkyo-ku, Japan, 113-8655

Sponsors and Collaborators

Eli Lilly and Company

Alzheimer's Therapeutic Research Institute

Investigators

• Study Director: 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); Eli Lilly and Company

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02008357
• Other Study ID Numbers: 15275; H8A-MC-LZAZ ( Other Identifier: Eli Lilly and Company )
• First Posted: December 11, 2013
• Last Update Posted: January 18, 2023
• Last Verified: January 15, 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eli Lilly and Company:

Cognition; Prevention

Additional relevant MeSH terms:

Cognition Disorders; Neurocognitive Disorders; Mental Disorders