An Open Label, Multicenter Study, Evaluating the Safety and Imaging Characteristics of 18F-AV-1451 in Cognitively Healthy Volunteers, Subjects With Mild Cognitive Impairment, and Subjects With Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 383
- 试验地点
- 27
- 主要终点
- Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline
研究概览
简要总结
A Phase 2/3 cross-sectional and longitudinal observational study evaluating imaging characteristics of flortaucipir in control subjects and patients with clinically defined MCI and AD dementia (AD).
详细描述
This study was conducted in 2 phases: a Phase 2 Exploratory Phase and a Phase 3 Confirmatory Phase. An overarching goal of the Exploratory Phase of this protocol was to further investigate the pattern of flortaucipir PET imaging across the disease course, in cognitively healthy subjects through patients with cognitive decline. To accomplish this goal, the protocol investigated flortaucipir results in younger and older cognitively healthy normal volunteers and patients with clinical diagnoses for cognitive complaints, ranging from MCI to mild and moderate AD dementia. Additionally, the Exploratory Phase of this protocol investigated relationships between flortaucipir PET signal and cognitive decline over the 18-month study period.
The second, Confirmatory Phase of the study was designed to provide independent validation of the relationships observed in the exploratory analyses of the first phase. In particular, the goal of the second phase was to confirm the relationship between flortaucipir uptake in the brain as measured by PET signals at baseline and the subsequent rate of cognitive decline observed over the 18-month longitudinal follow up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
盲法说明
Applies only to confirmatory phase: the independent readers are blinded to all clinical information.
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Exploratory Cognitively Healthy Subjects
- •≥ 20 to ≤ 40 years of age OR ≥ 50 years of age
- •Mini-mental state examination (MMSE) ≥ 29
- •No significant history of cognitive impairment
- •Exploratory MCI Subjects
- •≥ 50 years of age
- •MMSE ≥ 24
- •Have MCI consistent with National Institute on Aging-Alzheimer's Association (NIA-AA) working group's diagnostic guidelines for AD
- •Have a study partner that can report on subject's activities of daily living
- •Exploratory AD Subjects
- •≥ 50 years of age
- •MMSE > 10
- •Have possible or probable AD based on the NIA-AA working group's diagnostic guidelines for AD
- •Have a study partner that can report on subject's activities of daily living
- •Confirmatory Subjects
- •≥ 50 years of age
- •MMSE ≥ 20 and ≤ 27
- •Cognitively impaired subjects with either MCI or dementia with a suspected neurodegenerative cause
- •Have a study partner that can report on subject's activities of daily living
排除标准
- •Current clinically significant psychiatric disease
- •Evidence of structural brain abnormalities
- •History of moderate or severe traumatic brain injury
- •Current clinically significant cardiovascular disease or ECG abnormalities, or additional risk factors for Torsades de Pointes
- •Current clinically significant infectious disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer
- •History of alcohol or substance abuse or dependence
- •Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception
- •Have received or participated in a trial with investigational medications in the past 30 days
- •Have had a non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session.
研究组 & 干预措施
Exploratory Cognitively Healthy Subjects
Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie [mCi]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline.
干预措施: florbetapir F 18 (Drug)
Exploratory Cognitively Healthy Subjects
Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie [mCi]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline.
干预措施: Flortaucipir F18 (Drug)
Exploratory Cognitively Healthy Subjects
Subjects will receive an IV injection, 370 megabecquerel (MBq) (10 millicurie [mCi]), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline.
干预措施: Brain PET Scan (Procedure)
Exploratory MCI Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
干预措施: florbetapir F 18 (Drug)
Exploratory MCI Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
干预措施: Flortaucipir F18 (Drug)
Confirmatory Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline.
干预措施: Flortaucipir F18 (Drug)
Exploratory MCI Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
干预措施: Brain PET Scan (Procedure)
Exploratory AD Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
干预措施: florbetapir F 18 (Drug)
Exploratory AD Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
干预措施: Flortaucipir F18 (Drug)
Exploratory AD Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 at baseline. Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of flortaucipir at baseline, 9 months and 18 months.
干预措施: Brain PET Scan (Procedure)
Confirmatory Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline.
干预措施: florbetapir F 18 (Drug)
Confirmatory Subjects
Subjects will receive an IV injection, 370 MBq (10 mCi), single dose of florbetapir F 18 and flortaucipir at baseline.
干预措施: Brain PET Scan (Procedure)
结局指标
主要结局
Confirmatory Phase: Relationship Between Neocortical Flortaucipir Uptake and the Subsequent Rate of Cognitive Decline
时间窗: between baseline and 18 months
Confirm the relationship between neocortical flortaucipir uptake and the subsequent rate of cognitive decline at longitudinal follow up that was observed in the Exploratory Phase of the study. Patients were assigned to groups by majority classification of the flortaucipir positron emission tomography (PET) scan by five independent imaging physicians. Clinically meaningful cognitive and functional deterioration was defined as a 1 point or greater worsening on clinical dementia rating - sum of boxes (CDR-SB) score over the follow-up period.
Exploratory Phase: Cross-sectional Flortaucipir Imaging Results
时间窗: baseline scan
Flortaucipir standardized uptake value ratio (SUVr). A value of 1 signifies no flortaucipir activity above background, values greater than 1 signify increasing flortaucipir activity in the brain.
Exploratory Phase: Longitudinal Change in Tau Deposition Over Time, by Amyloid Status
时间窗: baseline and 18 months
Assess the rate of change of tau deposition as measured by flortaucipir uptake (SUVr) over time. Change = 18 months SUVr - baseline SUVr.
次要结局
- Confirmatory Phase: Diagnostic Performance of Flortaucipir Visual Read(baseline and 18 months)
- Exploratory Phase: Correlation Between Flortaucipir SUVr and Age(baseline scan)