Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)

Official 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 \[AD\]).

Eligibility Requirements

• Minimum Age: 65 Years
• Maximum Age: 85 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 1,169 participants

Study Arms

• 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).
• 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).

Interventions

• DRUG: Placebo — Administered IV
• DRUG: Solanezumab — Administered IV

Primary Outcomes

• Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score (Baseline, Week approximately 240)
• Change From Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) Score (Baseline, Week 336)

Secondary Outcomes

• 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)

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

Trial Locations

• University of Alabama at Birmingham, Birmingham, Alabama, United States
• Banner Health Research Institute, Phoenix, Arizona, United States
• Barrow Neurological Institute, Phoenix, Arizona, United States
• Banner Sun Health Research Institute, Sun City, Arizona, United States
• Institute for Memory Impairment & Neurological Disorders, Irvine, California, United States
• University of California - San Diego, La Jolla, California, United States
• University of Southern California School of Medicine, Los Angeles, California, United States
• University of California - Los Angeles, Los Angeles, California, United States
• Univ of California Irvine College of Medicine, Orange, California, United States
• Veterans Affairs Medical Center Palo Alto, Palo Alto, California, United States
• ...and 10 more locations

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) — STUDY_DIRECTOR
  Eli Lilly and Company

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