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Protocol H8A-MC-LZAZ (a) / ADC-040-A4 Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)

Description

Alzheimers disease (AD) is an age-related neurodegenerative disorder characterized by progressive decline in cognitive function and ability to perform activities of daily living,and ultimately can lead to death due to complications of the disease. Pathologic hallmarks of AD identified at autopsy include the presence of neuritic amyloid-B (AB) plaques. The AB plaques are protein deposits that accumulate outside and around neurons. The AB hypothesis for AD, which states that the production and deposition of AB (later forming neuritic AB plaques) is an early and necessary event in the pathogenesis of AD, suggests that treatments that slow the synthesis or deposition of AB, or that increase clearance, might be expected to slow the progression of AD. One such treatment is immunotherapy. Solanezumab is a monoclonal antibody that is being developed as a passive immunization therapy to reduce AB burden. Converging evidence from both genetic at risk and age at risk cohorts suggests that the pathophysiological process of AD begins well more than a decade before the clinical stage now recognized as AD dementia, and that neurodegenerationis already apparent by the stage of Mild Cognitive Impairment (MCI) / prodromal AD. The A4 study will target those participants with evidence of brain amyloid pathology on PET amyloid imaging who are still clinically normal but at high risk for cognitive decline (defined as preclinical AD).Objectives: The primary objective of this study is to test the hypothesis that solanezumab, administered as an intravenous infusion at a dose of 400 mg every 4 weeks for 3 years, will slow the cognitive decline with placebo in participants with preclinical AD. Study Design: This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing 400-mg solanezumab with placebo given as infusions once every 4 weeks 3 years in approximately 1150 outpatients with preclinical AD. Diagnosis and Main Criteria for Inclusion and Exclusions: Participants will be males and females 65 to 85 years old with preclinical AD. The study population is defined as participants with preclinical AD who have an MMSE score between 25 and 30, a Logical Memory test, part IIa score between 6 and 18, and a global CDR of 0; and having screening florabetapir PET scan indicating brain amyloid pathology.Efficacy: Preclinical Alzheimer Cognitive Composite (ADCS-PACC)Primary Analysis: The primary endpoint ADCS-PACC will be analyzed using an MMRM analysis.

Phase

Phase 3 - a treatment has shown activity against a particular disease, where it is either added to existing treatment or compared to the standard treatment.

Inclusion and Exclusion 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)

  • 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 resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen posttreatment
  • 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

Sites

  • California

    • University of Southern California School of Medicine, Los Angeles, California, 90033
    • University of Southern California School of Medicine, Los Angeles, California, 90033
    • University of California - Los Angeles, Los Angeles, California, 90095
    • Univ of California Irvine College of Medicine, Orange, California, 92868
    • Institute for Memory Impairment & Neurological Disorders, Irvine, California, 92697
    • University of California, Irvine, Irvine, California, 92697
    • University of California, Irvine, Irvine, California, 92697
    • University of California - San Diego, La Jolla, California, 92037
    • Stanford University, Palo Alto, California, 94304
    • University of California, Davis - Health Systems, Martinez, California, 94553
  • Nevada

    • Cleveland Clinic of Las Vegas, Las Vegas, Nevada, 89106
  • Arizona

    • Banner Sun Health Research Institute, Sun City, Arizona, 85351
    • Banner Sun Health Research Institute, Sun City, Arizona, 85351
    • Banner Health Research Institute, Phoenix, Arizona, 85006
  • Utah

    • University of Utah School of Medicine, Salt Lake City, Utah, 84132
  • Oregon

    • Oregon Health and Science University, Portland, Oregon, 97239
  • Washington

    • University of Washington School of Medicine, Seattle, Washington, 98108
    • University of Washington School of Medicine, Seattle, Washington, 98108
  • Texas

    • University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, 75390
    • Baylor College of Medicine, Houston, Texas, 77030
  • Oklahoma

    • Tulsa Clinical Research LLC, Tulsa, Oklahoma, 74104
  • Nebraska

    • Univ of Nebraska Med Center, Omaha, Nebraska, 68198
  • Kansas

    • University of Kansas Hospital, Fairway, Kansas, 66205
  • Minnesota

    • Mayo Clinic, Rochester, Minnesota, 55905
  • Iowa

    • University of Iowa, Iowa City, Iowa, 52242
  • Missouri

    • Washington University School of Medicine, St. Louis, Missouri, 63110
    • Washington University School of Medicine, St. Louis, Missouri, 63110
  • Wisconsin

    • University of Wisconsin-Madison Hospital and Health Clinic, Madison, Wisconsin, 53705
  • Illinois

    • Rush Alzheimer's Disease Center, Chicago, Illinois, 60612
    • Northwestern University, Chicago, Illinois, 60611
  • Alabama

    • University of Alabama at Birmingham, Birmingham, Alabama, 35294
  • Indiana

    • Indiana University School of Medicine, Indianapolis, Indiana, 46202
  • Kentucky

    • University of Kentucky, Lexington, Kentucky, 40504
  • Georgia

    • Emory University, Atlanta, Georgia, 30322
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