Clinical trial NCT02008357: Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss
Official title: Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cognition Disorders
Keywords: Cognition
Prevention
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Alzheimer's Therapeutic Research Institute
First posted: 2013-12-11
Enrollment: 1169
Sex: ALL
Minimum age (years): 65
Maximum age (years): 85
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 \[AD\]).

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.

Eligibility 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

Primary outcomes:
measure: Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score
timeFrame: Baseline, Week approximately 240
measure: Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score
timeFrame: Baseline, Week 336
Secondary outcomes:
measure: Change From Baseline in Cognitive Function Index (CFI)
timeFrame: Baseline, Week approximately 240
measure: Change From Baseline in Cognitive Function Index (CFI)
timeFrame: Baseline, Week 336
measure: Change From Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Questionnaire (ADCS-ADL-Prevention Questionnaire) Score
timeFrame: Baseline, Week approximately 240
measure: Change From Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Questionnaire (ADCS-ADL-Prevention Questionnaire) Score
timeFrame: Baseline, Week 336
measure: Change From Baseline in Mean Composite Standardized Uptake Value Ratio (SUVr)
timeFrame: Baseline, Week approximately 240
measure: Change From Baseline in Cerebrospinal Fluid (CSF) Tau Biomarkers
timeFrame: Baseline, Week approximately 240
measure: Change From Baseline of Cerebrospinal Fluid (CSF) Concentrations of Amyloid Beta (Aβ)
timeFrame: Baseline, Week approximately 240
measure: Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)
timeFrame: Baseline, Week approximately 240
measure: Change From Baseline on the Clinical Dementia Rating-Sum of Boxes Score (CDR-SB)
timeFrame: Baseline, Week 336
measure: Change From Baseline on the Computerized Cognitive Composite (C3)
timeFrame: Baseline, Week 336
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner Health Research Institute
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Irvine
country: United States
facility: Institute for Memory Impairment & Neurological Disorders
state: California
city: La Jolla
country: United States
facility: University of California - San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California School of Medicine
state: California
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: Orange
country: United States
facility: Univ of California Irvine College of Medicine
state: California
city: Palo Alto
country: United States
facility: Veterans Affairs Medical Center Palo Alto
state: California
city: Sacramento
country: United States
facility: Sutter Medical Group
state: California
city: San Francisco
country: United States
facility: Univ of California San Francisco
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Walnut Creek
country: United States
facility: University of California, Davis - Health Systems
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic-Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: Wien Center for Clinical Research
state: Florida
city: Orlando
country: United States
facility: Compass Research - Orlando
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: The Villages
country: United States
facility: Compass Research -The Villages
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute at Palm Beach Neurology
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush Alzheimer's Disease Center
state: Illinois
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Univ of Nebraska Med Center
state: Nebraska
city: Las Vegas
country: United States
facility: Cleveland Clinic of Las Vegas
state: Nevada
city: Amherst
country: United States
facility: Dent Neurological Institute
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Beachwood
country: United States
facility: Case Western Reserve University
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Clinical Research LLC
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Drexel University College of Medicine at EPPI
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Roper Hospital
state: South Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Seattle
country: United States
facility: University of Washington School of Medicine
state: Washington
city: Madison
country: United States
facility: University of Wisconsin-Madison Hospital and Health Clinic
state: Wisconsin
city: Parkville
country: Australia
facility: 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.
state: Victoria
city: London
country: Canada
facility: 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.
city: Toronto
country: Canada
facility: 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.
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
city: Vancouver
country: Canada
facility: 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.
city: Bunkyo-ku
country: Japan
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: 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
References:
citation: 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.
citation: 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.