Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,736
- 试验地点
- 269
- 主要终点
- Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)
研究概览
简要总结
The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer's disease.
Additional participants will be enrolled to an addendum safety cohort. The participants will be administered open-label donanemab.
Trial participants who were dosed with donanemab in the main study will be enrolled to a 3-year follow up addendum. No study drug will be administered during this follow up.
详细描述
TRAILBLAZER-ALZ 2 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of N3pG antibody (donanemab) in participants with early symptomatic AD (prodromal AD and mild dementia due to AD) with the presence of brain amyloid and tau pathology.
Following the double-blind 76-week main study period, a double-blind 78-week long-term extension period is added to further evaluate donanemab efficacy and safety over time. Participants from the addendum safety cohort are not eligible for the extension period.
Participants previously dosed with donanemab in the main study will be monitored to track re-accumulation of amyloid plaque for 3 years.
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
- •Meet 18F flortaucipir PET scan (central read) criteria - does not apply to safety cohort
- •Meet 18F florbetapir PET scan (central read) criteria
- •Have a study partner who will provide written informed consent to participate
排除标准
- •Contraindication to MRI or PET scans
- •Current treatment with immunoglobulin G (IgG) therapy
研究组 & 干预措施
Donanemab
Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks
干预措施: Donanemab (Drug)
Placebo
Participants received placebo given IV.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population)
时间窗: Baseline, Week 76
Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the 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. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Overall Population)
时间窗: Baseline, Week 76
Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the 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 adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline acetylcholinesterase inhibitor (AchI)/Memantine use.
次要结局
- Change From Baseline on the Mini Mental State Examination (MMSE) Score (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population)(Baseline, Week 76)
- Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline on the Mini Mental State Examination (MMSE) Score (Overall Population)(Baseline, Week 76)
- Number or Participants With Anti-Donanemab Antibodies(Baseline through Week 76)
- Change From Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Overall Population)(Baseline, Week 76)
- Change From Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab(Week 16 to week 20)
- Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score (Intermediate (Low-medium) Tau Population)(Baseline, Week 76)
- Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan(Baseline, Week 76)
- Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan(Baseline, Week 76)
- Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score (Overall Population)(Baseline, Week 76)
- Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)(Baseline, Week 76)