Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 327
- 试验地点
- 69
- 主要终点
- Change From Baseline to End Time Point in Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability and effect of study drug LY3372689 in participants with 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 22 to 30 (inclusive) at screening
- •CDR global score of 0.5 to 1.0 (inclusive), with a memory box score ≥0.
- •Meet 18F flortaucipir positron emission tomography (PET) scan (central analysis) criteria
- •Have a study partner who will provide written informed consent to participate
排除标准
- •Contraindication to MRI or PET scans
- •Have known allergies to LY3372689, related compounds, or any components of the formulations
研究组 & 干预措施
0.75 Milligram (mg) LY3372689
Double-blind treatment period: Participants received 0.75 mg LY3372689 administered orally once daily for up to 124 weeks.
Post treatment follow up period: Participants who received 0.75 mg LY3372689 during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring.
Post treatment observational extension period: Participants who received 0.75 mg LY3372689 during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring.
干预措施: LY3372689 (Drug)
3 mg LY3372689
Double-blind treatment period: Participants received 3 mg LY3372689 administered orally once daily for up to 124 weeks.
Post treatment follow up period: Participants who received 3 mg LY3372689 during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring.
Post treatment observational extension period: Participants who received 3 mg LY3372689 during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring.
干预措施: LY3372689 (Drug)
Placebo
Double-blind treatment period: Participants received placebo administered orally once daily for up to 124 weeks.
Post treatment follow up period: Participants who received placebo during the double-blind treatment period entered a post-treatment follow-up period for 4 weeks after last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety monitoring.
Post treatment observational extension period: Participants who received placebo during the double-blind treatment period had the option to enter post-treatment observational extension period for approximately 9 months on average since last blinded treatment dose. No study intervention was administered during this period, and participants were followed for safety, other/exploratory efficacy and biomarker monitoring.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to End Time Point in Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)
时间窗: Baseline, Week 100
iADRS is a simple linear combination of scores from 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). It is used to assess whether LY3372689 slows down the cognitive and functional decline associated with early symptomatic Alzheimer's Disease, compared to placebo. The iADRS score ranges from 0 to 144 with lower scores indicating worse performance and higher score better performance. Change from baseline was calculated using Bayesian disease progression model (DPM) adjusted for age at baseline, AChEI/Memantine use at baseline, pooled investigator. Data presented are posterior mean with 95% credible interval.
次要结局
- Change From Baseline to End Time Point in iADRS (Overall Population)(Baseline, Week 100)
- Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) (Overall Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) (Overall Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Mini Mental State Examination (MMSE) (Overall Population)(Baseline, Week 76)
- Change From Baseline to End Time Point In Brain Tau Deposition as Measured by Flortaucipir F18 Positron Emission Tomography (PET) Scan (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline to End Time Point In Brain Tau Deposition as Measured by Flortaucipir F18 Positron Emission Tomography (PET) Scan (Overall Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline to End Time Point in Volumetric Magnetic Resonance Imaging (vMRI) Measures (Overall Population)(Baseline, Week 76)
- Pharmacokinetics (PK): Plasma Concentrations of LY3372689(Week 64: Post-dose)