Assessment of Safety, Tolerability and Efficacy of LY3002813 in Early Symptomatic Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 272
- 试验地点
- 61
- 主要终点
- Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS) Score
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and efficacy of LY3002813 in early symptomatic Alzheimer's disease.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months.
- •MMSE score of 20 to 28 (inclusive) at baseline or an acceptable historical flortaucipir PET scan within 6 months prior to baseline that meets the central read criteria.
- •Meet 18F flortaucipir PET scan eligibility criteria.
- •Meet 18F florbetapir PET scan (central read) eligibility criteria.
排除标准
- •Have a history of long QT syndrome.
- •Have received treatment with a stable dose of an acetylcholinesterase inhibitor (AChEI) and/or memantine for less than 2 months before randomization.
- •Contraindication to MRI.
研究组 & 干预措施
Donanemab Monotherapy (Donanemab-M)
Participants received 700 milligram (mg) donanemab intravenously (IV) every 4 weeks (Q4W) x 3 doses, then 1400 mg donanemab IV Q4W for up to 72 weeks.
干预措施: Donanemab (Drug)
Placebo
Participants received placebo IV Q4W for up to 72 weeks.
干预措施: Placebo (Drug)
Donanemab in Combination With LY3202626 (Donanemab-C)
Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W in combination with 12 mg of LY3202626 orally for up to 72 weeks.
As per protocol amendment (d) approved on Oct 9, 2018, donanemab in combination with LY3202626 (donanemab-C) arm discontinued as there was a low probability of identifying a statistically significant effect of 12mg of LY3202626 slowing cognitive decline.
干预措施: Donanemab (Drug)
Donanemab in Combination With LY3202626 (Donanemab-C)
Participants received 700 mg donanemab IV Q4W x 3 doses, then 1400 mg donanemab IV Q4W in combination with 12 mg of LY3202626 orally for up to 72 weeks.
As per protocol amendment (d) approved on Oct 9, 2018, donanemab in combination with LY3202626 (donanemab-C) arm discontinued as there was a low probability of identifying a statistically significant effect of 12mg of LY3202626 slowing cognitive decline.
干预措施: LY3202626 (Drug)
结局指标
主要结局
Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS) Score
时间窗: Baseline, 76 Weeks
Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the cognitive and functional decline associated with AD compared with placebo. iADRS is a simple linear combination of 13-item alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. Least Squares (LS) Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, acetylcholinesterase inhibitor (AChEI) and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
次要结局
- Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan(Baseline, 76 Weeks)
- Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score(Baseline, 76 Weeks)
- Change From Baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score(Baseline, 76 Weeks)
- Change From Baseline in the Mini Mental State Examination (MMSE) Score(Baseline, 76 Weeks)
- Change From Baseline in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-iADL) Score(Baseline, 76 Weeks)
- Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan(Baseline, 76 Weeks)
- Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)(Baseline, 76 Weeks)