Effect of LY3202626 on Alzheimer's Disease Progression as Measured by Cerebral ¹⁸F-AV-1451 Tau-PET in Mild Alzheimer's Disease Dementia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 316
- 试验地点
- 50
- 主要终点
- Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks
研究概览
简要总结
The main purpose of this study is to evaluate the safety and the effect on brain tau of the study drug LY3202626 in participants with mild Alzheimer's disease (AD) dementia.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Present with mild AD dementia based on the National Institute on Aging (NIA) and the Alzheimer's Association (AA) disease diagnostic criteria as determined by a qualified clinician approved by the Sponsor or designee.
- •Mini-Mental State Examination score of 20 to 26 inclusive at screening visit.
- •Has a florbetapir PET scan consistent with the presence of amyloid pathology at screening.
排除标准
- •Significant neurological disease affecting the central nervous system (CNS), other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures (except febrile childhood seizures).
- •Ocular pathology that significantly limits ability to reliably evaluate vision or the retina.
- •Use of strong inducers of cytochrome P450 3A (CYP3A).
- •Sensitivity to florbetapir or ¹⁸F-AV-
- •Contraindication to MRI or PET or poor venous access for blood draws.
研究组 & 干预措施
Dose 1 LY3202626
3 mg LY3202626 given orally once daily for 52 weeks.
干预措施: LY3202626 (Drug)
Dose 2 LY3202626
12 mg LY3202626 given orally once daily for 52 weeks.
干预措施: LY3202626 (Drug)
Placebo
Placebo given orally once daily for 52 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks
时间窗: Baseline, Week 52
The 18F-AV-1451 PET tracer assesses change from baseline in the pharmacodynamic effect of 3 mg and 12 mg doses of LY3202626 in participants with mild Alzheimer's disease (AD), compared with placebo at Week 52.The SUVr of ¹⁸F-AV-1451 was modeled using analysis of covariance (ANCOVA) to include the fixed, categorical effects of treatment dose, and the continuous, fixed covariate of baseline Tau PET SUVr and age at baseline.
次要结局
- Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve at Steady State (AUC [T,SS]) of LY3202626(Week 2, 4, and 12: Predose and Postdose prior to departing; Week 8 and 16: Postdose after arriving and prior to departing; Week 24: Postdose after cognitive testing)
- Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA)(Week 52)
- Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings(Week 52)
- Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores(Baseline through Week 52)
- Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration(Baseline, Week 52)
- Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog₁₃)(Baseline, Week 52)
- Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL)(Baseline, Week 52)
- Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS)(Baseline, Week 52)