A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Intrathecally Administered ALN-APP in Patients With Cerebral Amyloid Angiopathy (CAA)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 210
- 试验地点
- 115
- 主要终点
- Double-blind Treatment Period: Annualized Rate of New Lobar Cerebral Microbleeds (CMBs) Assessed on Magnetic Resonance Imaging (MRI) of Brain in Patients with Sporadic Cerebral Amyloid Angiopathy (sCAA)
研究概览
简要总结
The purpose of the study is to evaluate the effect of ALN-APP on measures of CAA disease progression and to characterize the safety, tolerability, and pharmacodynamics (PD) of ALN-APP in adult patients with sporadic CAA (sCAA) and Dutch-type CAA (D-CAA). The study will be conducted over 2 periods: a 24-month double-blind treatment period and an optional 18-month open-label extension (OLE) period. The estimated duration of study participation, inclusive of screening, treatment, and additional safety follow-up, is up to 50 months.
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
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(sporadic CAA patients):
- •Is 50 years or older
- •Has probable CAA per the Boston Criteria Version 2.0
- •Inclusion Criteria (Dutch-type CAA patients):
- •Is 30 years or older
- •Has known E693Q amyloid precursor protein (APP) gene mutation for Dutch-type CAA
排除标准
- •Moderate or severe stage Alzheimer's disease (AD) or significant cognitive impairment (CI)
- •Has a history of previous clinical intracerebral hemorrhage (ICH) with onset less than 90 days prior to anticipated randomization in the study
- •Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×upper limit of normal (ULN) at Screening
- •Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2 at Screening
- •Has recently received an investigational agent
- •Has had treatment with amyloid-targeting antibody
- •Note: other protocol defined inclusion / exclusion criteria apply
研究组 & 干预措施
Placebo/ALN-APP
Participants will be administered multiple doses of placebo during the double-blind treatment period. Participants who continue into the optional open-label extension period will be administered multiple doses of ALN-APP.
干预措施: ALN-APP (Drug)
Placebo/ALN-APP
Participants will be administered multiple doses of placebo during the double-blind treatment period. Participants who continue into the optional open-label extension period will be administered multiple doses of ALN-APP.
干预措施: Placebo (Drug)
ALN-APP
Participants will be administered multiple doses of ALN-APP during the double-blind treatment period and optional open-label extension period.
干预措施: ALN-APP (Drug)
结局指标
主要结局
Double-blind Treatment Period: Annualized Rate of New Lobar Cerebral Microbleeds (CMBs) Assessed on Magnetic Resonance Imaging (MRI) of Brain in Patients with Sporadic Cerebral Amyloid Angiopathy (sCAA)
时间窗: Up to 24 months
次要结局
- Double-blind Treatment Period: Change from Baseline Over Time in Cerebrovascular Vasoreactivity Measured by Blood Oxygenation Level Dependent (BOLD) Parameters with Visual-evoked Functional MRI(Up to 24 months)
- Double-blind Treatment Period: Change from Baseline Over Time in the Total Cerebral Amyloid Angiopathy (CAA) Small Vessel Disease Score Assessed on MRI of Brain(Up to 24 months)
- Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Alpha (sAPPα) Concentration in Cerebrospinal Fluid (CSF)(Up to 24 months)
- Double-blind Treatment Period: Global Rank Based on Severity, Count, Symptom Burden, and Timing of New Clinical Hemorrhagic Events and Hemorrhagic Lesions Assessed on MRI of Brain(Up to 24 months)
- Double-blind Treatment Period: Change from Baseline in Soluble Amyloid Precursor Protein Beta (sAPPβ) Concentration in CSF(Up to 24 months)
- Double-blind Treatment Period: Incidence of New Cerebral Hemorrhagic Lesions and White Matter Hyperintensities Assessed on MRI of Brain(Up to 24 months)
- Double-blind Treatment Period and Open-label Extension (OLE) Period: Frequency of Adverse Events(Up to 48 months)