Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease(A4 Study)
H8A-MC-LZAZ
Eli Lilly Japan K.K.
5-1-28, Isogamidori, Chuo-ku, Kobe, Hyogo
+81-120-023-812
LTG_CallCenter@lists.lilly.com
Eli Lilly Japan K.K.
5-1-28, Isogamidori, Chuo-ku, Kobe, Hyogo
+81-120-023-812
LTG_CallCenter@lists.lilly.com
completed
Sept. 28, 2016
1150
Interventional
This is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing
solanezumab with placebo given as infusions once every 4 weeks over 240 weeks in approximately 1150 subjects with preclinical AD, defined as having evidence of elevated brain amyloid pathology before the stage of clinically evident cognitive impairment. Additionally, subjects completing the Placebo-Controlled Period of the study can opt to participate in the Open-Label Period of the study that will last for up to 204 weeks or until the primary analyses of the placebo-controlled period of the study are completed and reviewed.
treatment purpose / prevention purpose
3
MMSE score at screening of 25 to 30
global CDR score at screening of 0
Logical Memory II score at screening of 6 to 18
Florbetapir PET scan that shows evidence of brain amyloid pathology
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 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
65age old over
85age old under
Both
Preclinical AD
investigational material(s)
Generic name etc : Solanezumab
INN of investigational material : Solanezumab
Therapeutic category code : 119 Other agents affecting central nervous system
Dosage and Administration for Investigational material : Solanezumab Arm: During Placebo-Controlled Period from Week 0 through Week 236, Solanezumab dose escalation from 400 mg IV infusion every 4 weeks for at least 2 doses, and then 800 mg IV infusion every 4 weeks for at least 2 doses, and 1600 mg IV infusion every 4 weeks. During Open-Label Period from Week 240 through end of the study Week 440, 1600 mg IV infusion every 4 weeks (subjects who are receiving 400 mg or 800 mg every 4 weeks when they complete the Placebo-Controlled Period may be maintained at the dose in the Open-Label Period.Placebo Arm: During Placebo-Controlled Period from Week 0 through Week 236, Placebo IV infusion every 4 weeks. During Open-Label Period from Week 240 through end of the study Week 440, Solanezumab dose escalation from 400 mg IV infusion every 4 weeks for at least 2 doses, and then 800 mg IV infusion every 4 weeks for at least 2 doses, and 1600 mg IV infusion every 4 weeks. ).
control material(s)
Generic name etc : Placebo
INN of investigational material : -
Therapeutic category code : --- Other
Dosage and Administration for Investigational material : an intravenous infusion every 4 weeks for 240 weeks
efficacy
confirmatory
Change from Baseline of the Preclinical Alzheimer Cognitive Composite (PACC) [ Time Frame: Baseline, Week 240; Baseline, Week 336 ]
safety
efficacy
confirmatory
1.Change from Baseline in Cognitive Function Index (CFI) [ Time Frame: Baseline, Week 240; Baseline, Week 336 ]
2.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 ]
3.Change from Baseline in Mean Composite Standardized Uptake Value Ratio (SUVr) [ Time Frame: Baseline, Week 240 ]
4.Change from Baseline in Cerebrospinal Fluid (CSF) Tau Biomarkers [ Time Frame: Baseline, Week 240 ]
5.Change from Baseline of CSF Concentrations of Amyloid Beta (Abeta) [ Time Frame: Baseline, Week 240 ]
6.Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline, Week 240 ]
7.Change from Baseline on the Clinical Dementia Rating-Sum of Boxes score (CDR-SB) [ Time Frame: Baseline, Week 336 ]
8.Change from Baseline on the Computerized Cognitive Composite (C3) [ Time Frame: Baseline, Week 336 ]
