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

Lilly

Status and phase: Completed; Phase 3

Conditions: Cognition Disorders

Treatments: Drug: Solanezumab; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02008357

15275

H8A-MC-LZAZ (Other Identifier)

Details and patient eligibility

About

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]).

Full 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.

Enrollment: 1,169 patients

Sex: All

Ages: 65 to 85 years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,169 participants in 2 patient groups, including a placebo group

Solanezumab/Solanezumab

Experimental group

Description:

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).

Treatment:

Drug: Solanezumab

Placebo/Solanezumab

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo

Drug: Solanezumab