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

NCT02008357 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 15275H8A-MC-LZAZ
• Study Type: interventional
• Target: 1,169
• Locations: 4 countries
• Sites: 68

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 \[AD\]).

Conditions

Cognition Disorders

Keywords

Cognition; Prevention

Outcome Measures

Primary Outcomes (2)

• Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score

  PACC has 4 components: Free and Cued Selective Reminding Test (0 (worst)-96 (best recall); Delayed Paragraph Recall test (Range 0 (worst)-25 (best recall); Wechsler Adult Intelligence scale: Digit Symbol Substitution Test (DSST): (ranges 0 \[none\]-91 \[best performance\]) and Mini Mental State Examination (Range 0 \[worst\] - 30 \[best performance\]). Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. Thus, a change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.

  Baseline, Week approximately 240

• Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score

  PACC has 4 components: Free and Cued Selective Reminding Test (0 (worst)-96 (best recall); Delayed Paragraph Recall test (Range 0 (worst)-25 (best recall); Wechsler Adult Intelligence scale: Digit Symbol Substitution Test (DSST): (ranges 0 \[none\]-91 \[best performance\]) and Mini Mental State Examination (Range 0 \[worst\] - 30 \[best performance\]). Component scores are transformed using an established normalization method into z-scores. Each of 4 component change scores is divided by baseline sample standard deviation (SD) of that component. These z scores are summed to form the composite score. Thus, a change of 1 baseline standard deviation on each component would correspond to a 4-point change on the composite. A z-score of 0 is equal to the mean and implies how many SD higher or lower score as compared with baseline score, with increase signifying improvement.

  Baseline, Week 336

Secondary Outcomes (10)

• Change From Baseline in Cognitive Function Index (CFI)

  Baseline, Week approximately 240

• Change From Baseline in Cognitive Function Index (CFI)

  Baseline, Week 336

• Change From Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Questionnaire (ADCS-ADL-Prevention Questionnaire) Score

  Baseline, Week approximately 240

• Change From Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Questionnaire (ADCS-ADL-Prevention Questionnaire) Score

  Baseline, Week 336

• Change From Baseline in Mean Composite Standardized Uptake Value Ratio (SUVr)

  Baseline, Week approximately 240

Study Arms (2)

Solanezumab/Solanezumab

EXPERIMENTAL

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).

Drug: Solanezumab

Placebo/Solanezumab

PLACEBO COMPARATOR

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).

Drug: Placebo; Drug: Solanezumab

Interventions

Placebo DRUG

Administered IV

Placebo/Solanezumab

Solanezumab DRUG

Administered IV

Also known as: LY2062430

Placebo/Solanezumab; Solanezumab/Solanezumab

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Alzheimer's Therapeutic Research Institute: collaborator

Study Sites (68)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Banner Health Research Institute

Phoenix, Arizona, 85006, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Institute for Memory Impairment & Neurological Disorders

Irvine, California, 92697, United States

Location

University of California - San Diego

La Jolla, California, 92037, United States

Location

University of Southern California School of Medicine

Los Angeles, California, 90033, United States

Location

University of California - Los Angeles

Los Angeles, California, 90095, United States

Location

Univ of California Irvine College of Medicine

Orange, California, 92868, United States

Location

Veterans Affairs Medical Center Palo Alto

Palo Alto, California, 94304, United States

Location

Sutter Medical Group

Sacramento, California, 95816, United States

Location

Univ of California San Francisco

San Francisco, California, 94158, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

University of California, Davis - Health Systems

Walnut Creek, California, 94598, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Georgetown University Hospital

Washington D.C., District of Columbia, 20057, United States

Location

Howard University Hospital

Washington D.C., District of Columbia, 20060, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

Wien Center for Clinical Research

Miami Beach, Florida, 33140, United States

Location

Compass Research - Orlando

Orlando, Florida, 32806, United States

Location

University of South Florida

Tampa, Florida, 33613, United States

Location

Compass Research -The Villages

The Villages, Florida, 32162, United States

Location

Premiere Research Institute at Palm Beach Neurology

West Palm Beach, Florida, 33407, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush Alzheimer's Disease Center

Chicago, Illinois, 60612, United States

Location

Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas Hospital

Fairway, Kansas, 66205, United States

Location

University of Kentucky

Lexington, Kentucky, 40504, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808-4124, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21093, United States

Location

Brigham and Womens Hospital

Boston, Massachusetts, 02115, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Univ of Nebraska Med Center

Omaha, Nebraska, 68198, United States

Location

Cleveland Clinic of Las Vegas

Las Vegas, Nevada, 89106, United States

Location

Dent Neurological Institute

Amherst, New York, 14226, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14620, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Case Western Reserve University

Beachwood, Ohio, 44122, United States

Location

Tulsa Clinical Research LLC

Tulsa, Oklahoma, 74104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Drexel University College of Medicine at EPPI

Philadelphia, Pennsylvania, 19102, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02906, United States

Location

Roper Hospital

Charleston, South Carolina, 29401, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

University of Washington School of Medicine

Seattle, Washington, 98108, United States

Location

University of Wisconsin-Madison Hospital and Health Clinic

Madison, Wisconsin, 53705, United States

Location

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, 3010, Australia

Location

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, N6C 0A7, Canada

Location

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, M3B2S7, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, M4N 3M5, Canada

Location

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, V6T 2B5, Canada

Location

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, 113-8655, Japan

Location

Related Publications (8)

• Hibar DP, Bauer A, Rabe C, Borlinghaus N, Jethwa A, Kollmorgen G, Di Domenico A, Zetterberg H, Blennow K, Masters CL, Sperling RA, Bittner T. Elecsys pTau217 plasma immunoassay detection of amyloid pathology in clinical cohorts. Alzheimers Dement. 2026 Jan;22(1):e71009. doi: 10.1002/alz.71009.

  PMID: 41537338 DERIVED

• 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.

  PMID: 41085172 DERIVED

• 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.

  PMID: 41001450 DERIVED

• 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.

  PMID: 40476544 DERIVED

• 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.

  PMID: 40440591 DERIVED

• 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.

  PMID: 37458272 DERIVED

• 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.

  PMID: 35543002 DERIVED

• 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.

  PMID: 35197359 DERIVED

Related Links

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

MeSH Terms

Conditions

Cognition Disorders

Interventions

solanezumab

Condition Hierarchy (Ancestors)

Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

Per protocol and SAP, delayed-start analyses were not conducted because no treatment difference was observed at the end of the double-blind (placebo-controlled) period. Hence, data were not evaluated for outcome measure analyses (week 336), but safety data were analyzed for open-label extension period.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2013
• First Posted: December 11, 2013
• Study Start: February 28, 2014
• Primary Completion: December 27, 2022
• Study Completion: June 8, 2023
• Last Updated: December 28, 2023
• Results First Posted: December 28, 2023

Record last verified: 2023-12

Locations

JP (1); US (62); AU (1); CA (4)