An Open-label, Non-randomized, Multi-center Pivotal Phase 3 Study to Evaluate the Efficacy and Safety of PET Imaging With [18F]PI-2620 for the Detection of Tau Deposition When Compared to Post-mortem Histopathology (ADvance)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 45
- 主要终点
- Diagnostic Efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating tau neurofibrillary pathology associated with AD (NFT Score of B0 or B1 = negative)
研究概览
简要总结
This study is an open-label, multi-center, non-randomized pivotal Phase 3 study to assess the efficacy and safety of PET imaging with [18F]PI-2620 for detection of tau deposition in subjects with Alzheimer's disease (AD) and controls during lifetime when compared to histopathology obtained after death and completion of brain autopsy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Only subjects who meet all of the following criteria will be eligible for enrollment into the study:
- •Males and females aged 50 years and over
- •Have a projected life expectancy of ≤ 1 year as determined by the investigator (terminal medical condition including but not limited to end-stage dementia, end-stage congestive heart failure, end-stage chronic obstructive pulmonary disease (COPD), or end-stage cancer)
- •Written informed consent obtained from the subject and/or the subject's legally authorized representative (LAR), as applicable, to consent for study procedures and brain donation (consent consistent with the legal requirements of the State in which the subject dies)
- •Can tolerate study procedures including lying down in PET scanner. The investigator will carefully assess each subject and use medical judgment to determine whether the subject can tolerate the imaging procedure
排除标准
- •Subjects will be excluded from the enrollment if they:
- •Are receiving aggressive treatment with life sustaining measures (e.g. receiving chemotherapy; palliative chemotherapy is allowed)
- •Are known to have a structural brain lesion that would interfere either with PET imaging or pathological assessment (e.g. lesions are typically > 2 cm at their greatest extent and may include stroke, primary or metastatic neoplasm, other tumors or cystic lesions. Subjects with a history of major stroke or traumatic brain injury or other structural lesion as well as cases with a history of primary Central Nervous System (CNS) neoplasm or known metastatic cancer must be discussed with the study sponsor prior to enrollment)
- •Have suspected encephalopathy due to alcoholism or end-stage liver disease
- •Are known to have a Glomerular Filtration Rate below < 15 mL/min
- •Have received an investigational or approved therapy directly targeting amyloid or tau
- •Are females of childbearing potential who are pregnant, lactating or breastfeeding, or who are not using adequate contraception
- •Have implants such as implanted cardiac pacemakers or defibrillators, insulin pumps, cochlear implants, metallic ocular foreign body, implanted neural stimulators, CNS aneurysm clips and other medical implants that have not been certified for MRI, or history of claustrophobia in MRI (in case an MRI is planned to be performed)
研究组 & 干预措施
PI-2620 PET Scan
干预措施: [18F]PI-2620 (Drug)
结局指标
主要结局
Diagnostic Efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating tau neurofibrillary pathology associated with AD (NFT Score of B0 or B1 = negative)
时间窗: At autopsy, until study completion with an average of 1 year
\[18F\]PI-2620 PET scans will be classified as either tau-positive or tau-negative as defined by the reading methodology by each of the 5 independent readers blinded to the clinical and pathology information. NFT scores (as defined in Hyman et al. 2012) will be used as pathology assessment SoT (standard of truth). Tau neurofibrillary pathology associated with AD is defined as either negative with NFT Scores of B0 or B1 or positive NFT Scores of B2 or B3. The \[18F\]PI-2620 PET visual assessment will be compared with the pathology assessment to derive sensitivity and specificity estimates for each individual reader. Sensitivity and specificity are percentages that can range from 0 to 100%. The primary endpoint is considered to be met if for the same 3 out of 5 readers, the lower bound of the 95% CIs for both sensitivity and specificity are ≥ 50%.
次要结局
- Diagnostic efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating levels of AD neuropathologic change (ADNC) ('No' or 'Low' levels of ADNC = negative)(At autopsy, until study completion with an average of 1 year)
- Diagnostic Efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating tau neurofibrillary pathology associated with AD (NFT Score of B0, B1 or B2 = negative)(At autopsy, until study completion with an average of 1 year)
- Diagnostic efficacy of the visual assessment of [18F]PI-2620 PET imaging, in correctly differentiating levels of ADNC ('No', 'Low' or 'Intermediate" levels of ADNC = negative)(At autopsy, until study completion with an average of 1 year)
- Inter-reader agreement for the visual assessment of [18F]PI-2620 PET images(Baseline scan)