Effect of Passive Immunization on the Progression of Mild Alzheimer's Disease: Solanezumab (LY2062430) Versus Placebo
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2,129
- 试验地点
- 119
- 主要终点
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 14 Item Subscore (ADAS-Cog14)
研究概览
简要总结
To test the idea that solanezumab will slow the cognitive decline of Alzheimer's Disease (AD) as compared with placebo in participants with mild AD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD
- •Has a Modified Hachinski Ischemia Scale score of less than or equal to 4
- •Has a Mini-Mental State Examination (MMSE) score of 20 through 26 at Screening visit
- •Has a Geriatric Depression Scale score of less than or equal to 6 (on the staff-administered short form)
- •Has had a magnetic resonance imaging (MRI) or computerized tomography (CT) scan performed within the past 2 years that has confirmed no findings inconsistent with a diagnosis of AD
- •Has a florbetapir positron emission tomography (PET) scan or cerebrospinal fluid (CSF) result consistent with the presence of amyloid pathology at screening
排除标准
- •Does not have a reliable caregiver who is in frequent contact with the participant (defined as at least 10 hours per week), will accompany the participant to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications
- •Meets National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS/AIREN) criteria for vascular dementia
- •Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study; or has a life expectancy of <2 years
- •Has had a history within the last 5 years of a serious infectious disease affecting the brain or head trauma resulting in protracted loss of consciousness
- •Has 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 a normal prostate-specific antigen posttreatment
- •Has a known history of human immunodeficiency virus (HIV), clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions
- •Has received acetylcholinesterase inhibitor (AChEIs), memantine and/or other AD therapy for less than 4 months or has less than 2 months of stable therapy on these treatments
- •Has received medications that affect the central nervous system (CNS), except treatments for AD, for less than 4 weeks
- •Has a history of chronic alcohol or drug abuse/dependence within the past 5 years
- •Has a Visit 1 MRI with results showing >4 Amyloid-related Imaging Abnormality (ARIA), -hemorrhage /hemosiderin deposition (ARIA-H) or presence of ARIA-E (edema/effusions)
研究组 & 干预措施
Solanezumab
Solanezumab 400 milligrams (mg) every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will take this regimen for up to an additional 208 weeks.
干预措施: Solanezumab (Drug)
Placebo
Placebo every 4 weeks for 76 weeks with an additional 4 weeks of assessments. Participants who complete the full 80 weeks of treatment/assessment and decide to continue will switch to solanezumab 400 mg every 4 weeks for up to an additional 208 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 14 Item Subscore (ADAS-Cog14)
时间窗: Baseline, Week 80
The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS that was used as the primary efficacy measure consists of 14 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze completion measures. The ADAS-Cog14 scale ranges from 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit.
次要结局
- Change From Baseline in Alzheimer's Disease Cooperative Study- Instrumental Activities of Daily Living (ADCS-iADL)(Baseline, Week 80)
- Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive 11 Item Subscore (ADAS-Cog11)(Baseline, Week 80)
- Change From Baseline in Mini-Mental State Examination (MMSE)(Baseline, Week 80)
- Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL)(Baseline, Week 80)
- Change From Baseline in Functional Activities Questionnaire (FAQ)(Baseline, Week 80)
- Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB)(Baseline, Week 80)
- Change From Baseline in Neuropsychiatric Inventory (NPI)(Baseline, Week 80)
- Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite)(Baseline, Week 80)
- Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD)(Baseline, Week 80)
- Change From Baseline in 5-Dimensional EuroQol Quality of Life Scale Proxy Version (EQ-5D Proxy)(Baseline, Week 80)
- Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS)(Baseline, Week 80)
- Percentage of Participants of Cognitive and Functional Responders(Baseline through Week 80)
- Change From Baseline in Plasma Amyloid-Beta (Aβ) Species(Baseline, Week 80)
- Change From Baseline in Volumetric Magnetic Resonance Imaging (vMRI)(Baseline, Week 80)
- Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Solanezumab (LY2062430)(Visit 2 (Post-dose), Visit 5, 9, 15 (Pre-dose, Post-dose) and Visit 22 (Pre-dose): Pre-dose before the infusion, Post-dose 30 minutes End of Infusion)
- Change From Baseline in Florbetapir Positron Emission Tomography (PET) Scan(Baseline, Week 80)
- Change From Baseline in Cerebrospinal Fluid (CSF) Aβ Levels(Baseline, Week 80)