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

• ClinicalTrials.gov Identifier: NCT02008357
• Recruitment Status: Active, not recruiting
• First Posted: December 11, 2013
• Last Update Posted: January 18, 2023
• Sponsor: Eli Lilly and Company
• Collaborator: Alzheimer's Therapeutic Research Institute
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: December 6, 2013
• First Posted Date: December 11, 2013
• Last Update Posted Date: January 18, 2023
• Actual Study Start Date: February 28, 2014
• Actual Primary Completion Date: December 27, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 14, 2018): Change from Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) [ Time Frame: Baseline, Week 240; Baseline, Week 336 ]
• Original Primary Outcome Measures (submitted: December 6, 2013): Change from Baseline of the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC) to Week 168 [ Time Frame: Baseline, Week 168 ]

Current Secondary Outcome Measures (submitted: November 14, 2018)

• Change from Baseline in Cognitive Function Index (CFI) [ Time Frame: Baseline, Week 240; Baseline, Week 336 ]
• Change from Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Questionnaire (ADCS-ADL-Prevention Questionnaire) Score [ Time Frame: Baseline, Week 240; Baseline, Week 336 ]
• Change from Baseline in Mean Composite Standardized Uptake Value Ratio (SUVr) [ Time Frame: Baseline, Week 240 ]
• Change from Baseline in Cerebrospinal Fluid (CSF) Tau Biomarkers [ Time Frame: Baseline, Week 240 ]
• Change from Baseline of CSF Concentrations of Amyloid Beta (Abeta) [ Time Frame: Baseline, Week 240 ]
• Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline, Week 240 ]
• Change from Baseline on the Clinical Dementia Rating-Sum of Boxes score (CDR-SB) [ Time Frame: Baseline, Week 336 ]
• Change from Baseline on the Computerized Cognitive Composite (C3) [ Time Frame: Baseline, Week 336 ]

Original Secondary Outcome Measures (submitted: December 6, 2013)

• Change from Baseline in Cognitive Function Index (CFI) to Week 156 [ Time Frame: Baseline, Week 156 ]
• Change from Baseline in Alzheimer's Disease Cooperative Study-Activities Daily Living-Prevention Instrument (ADCS-ADL-PI) Score to Week 156 [ Time Frame: Baseline, Week 156 ]
• Change from Baseline in Mean Composite Summary Uptake Value Ratio (SUVr) to Week 168 [ Time Frame: Baseline, Week 168 ]
• Change from Baseline in Cerebral Spinal Fluid (CSF) Tau Biomarkers to Week 168 [ Time Frame: Baseline, 168 Weeks ]
• Change from Baseline of Cerebrospinal Fluid (CSF) Concentrations of Amyloid Beta (Abeta) to Week 168 [ Time Frame: Baseline, 168 Weeks ]
• Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) to Week 168 [ Time Frame: Baseline, Week 168 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cognition Disorders

Intervention

• Drug: Placebo
  Administered IV
• Drug: Solanezumab
  Administered IV
  Other Name: LY2062430

Study Arms

• Experimental: Solanezumab

  Solanezumab (400-1600 milligrams) intravenously (IV) every 4 weeks for 240 weeks.

  Participants who enter the open-label extension will receive solanezumab IV.

  Intervention: Drug: Solanezumab
• Placebo Comparator: Placebo

  Placebo IV every 4 weeks for 240 weeks.

  Participants who enter the open-label extension will receive solanezumab IV.

  Interventions:

  • Drug: Placebo
  • Drug: Solanezumab

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: September 22, 2014): 1150
• Original Estimated Enrollment (submitted: December 6, 2013): 1000
• Estimated Study Completion Date: June 30, 2023
• Actual Primary Completion Date: December 27, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years to 85 Years (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Japan, United States

Administrative Information

• NCT Number: NCT02008357
• Other Study ID Numbers: 15275; H8A-MC-LZAZ ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Alzheimer's Therapeutic Research Institute

Investigators

• Study Director: 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

• PRS Account: Eli Lilly and Company
• Verification Date: January 15, 2023