A Randomized, Placebo-Controlled, Translational Study of ATH-1017 in Subjects With Mild to Moderate Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 13
- 主要终点
- Event-related Potential (ERP) P300 Latency at Baseline
研究概览
简要总结
This study is designed to evaluate treatment effects of ATH-1017 (fosgonimeton) in mild to moderate Alzheimer's subjects with a randomized treatment duration of 26-weeks.
详细描述
This study is designed to assess the correlation of the functional translational biomarker P300 latency and change in ADAS-Cog11 induced by ATH-1017 therapy, over 26-week randomized, double-blind treatment.
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
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 55 to 85 years
- •Mild-to-moderate AD dementia subjects, MMSE 14-24, CDR 1 or 2 at Screening
- •Clinical diagnosis of dementia, due probably to AD, by Revised National Institute on Aging-Alzheimer's Association criteria (McKhann, 2011)
- •Reliable and capable support person/caregiver
- •Treatment-free or receiving stable acetylcholinesterase inhibitor (AChEI) treatment, defined as:
- •Treatment-naïve, OR
- •Subjects are on a stable, approved dose of an AChEI (except for donepezil at 23 mg PO) for at least 3 months before Screening OR
- •Subjects who received an AChEI in the past and discontinued 4 weeks prior to Screening
排除标准
- •History of significant neurologic disease, other than AD, that may affect cognition, or concurrent with the onset of dementia
- •History of unexplained loss of consciousness, and epileptic fits (unless febrile)
- •Subject has atypical variant presentation of AD, if known from medical history, particularly non-amnestic AD
- •History of brain MRI scan indicative of any other significant abnormality
- •Hearing test result considered unacceptable for auditory ERP P300 assessment
- •Diagnosis of severe major depressive disorder even without psychotic features
- •Significant suicide risk
- •History within 2 years of Screening, or current diagnosis of psychosis
- •Myocardial infarction or unstable angina within the last 6 months
- •Clinically significant (in the judgment of the investigator) cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (note: pacemaker is acceptable)
- •Subject has either hypertension (supine diastolic blood pressure > 95 mmHg), or symptomatic hypotension in the judgment of the investigator
- •Clinically significant ECG abnormality at Screening
- •Renal insufficiency (serum creatinine > 2.0 mg/dL)
- •Hepatic impairment with alanine aminotransferase or aspartate aminotransferase > 2 times the upper limit of normal, or Child-Pugh class B and C
- •Malignant tumor within 3 years before Screening
- •Memantine in any form, combination or dosage within 4 weeks prior to Screening
- •Donepezil at 23 mg PO
- •The subject has received active amyloid or tau immunization (i.e., vaccination for Alzheimer's disease) at any time, or passive immunization (i.e., monoclonal antibodies for Alzheimer's disease) within 6 months of Screening
研究组 & 干预措施
Low Dose
Daily subcutaneous (SC) injection of Low Dose ATH-1017
干预措施: ATH-1017 (Drug)
High Dose
Daily subcutaneous (SC) injection of High Dose ATH-1017
干预措施: ATH-1017 (Drug)
Placebo
Daily subcutaneous (SC) injection of Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Event-related Potential (ERP) P300 Latency at Baseline
时间窗: At Baseline (Day 1)
ERP P300 was a method of recording brain activity elicited by external stimuli, for example (e.g.), an oddball auditory stimulus, particularly of working memory access. The participant had to perform a task related to auditory stimuli in order to assess the P300 component (latency). The stimulus consisted of an oddball paradigm with 2 sound stimuli. Stimuli were presented through headphones and auditory stimulation for P300 was assessed in a recording lasting up to 10 minutes. It was calculated as the average across the pre-dose values at Baseline visit. Baseline was defined as Day 1.
次要结局
- Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) at Baseline(At Baseline (Day 1))