A Randomized, Placebo-Controlled, Double-Blind Study of ATH-1017 Treatment 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
- 554
- 试验地点
- 1
- 主要终点
- Global Statistical Test (GST) Score
研究概览
简要总结
This study is designed to evaluate safety and efficacy of fosgonimeton (ATH-1017) in the treatment of mild to moderate Alzheimer's disease with a randomized treatment duration of 26-weeks.
详细描述
The study is designed to evaluate safety and efficacy of ATH-1017 in mild to moderate AD subjects, with randomized, parallel-arm treatment duration of 26 weeks, and based on clinical diagnostic criteria of Alzheimer's disease. Clinical efficacy is demonstrated by improvement in cognition and global/functional assessments comparing treatment to placebo.
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)
- •Body mass index (BMI) of ≥ 18 and ≤ 35 kg/m2 at Screening
- •Reliable and capable support person/caregiver
- •Treatment-free (subjects not receiving acetylcholinesterase inhibitor [AChEI] treatment), defined as:
- •Treatment-naïve, OR
- •Subjects who received an AChEI in the past and discontinued at least 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
- •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
- •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 cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (note: pacemaker is acceptable)
- •Subject has either hypertension or symptomatic hypotension
- •Clinically significant ECG abnormality at Screening
- •Chronic kidney disease with estimated glomerular filtration rate (eGFR) <45 mL/min
- •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
- •Acetylcholinesterase inhibitors in any dosage form
- •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
Dosage
Daily subcutaneous (SC) injection of 40mg 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
Global Statistical Test (GST) Score
时间窗: Baseline and Week 26
The Global Statistical Test (GST) score is a composite of cognition and function, calculated as the average of two change from baseline z-scores; the z-scores are calculated for the change from baseline scores for cognition (Alzheimer's Disease Assessment Scale-Cognitive Subscale \[ADAS-Cog11\]; lower value indicates improvement) and function (Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-item version \[ADCS-ADL23\] score; higher value indicates improvement). GST is a standardized score relative to the population mean. Therefore, a GST score of 0 is representative of the population mean. Since GST is a composite of two endpoints, a negative ADCS-ADL23 score is used in deriving GST. Therefore, a lower score indicates improvement, and a higher score indicates worsening. There are no defined clinically relevant thresholds for this GST score.
次要结局
- Alzheimer's Disease Cooperative Study - Activities of Daily Living, 23-Item Version (ADCS-ADL23) Change From Baseline(Baseline and Week 26)
- Plasma Neurofilament Light Chain (NfL) Concentrations Change From Baseline(Baseline and Week 26)
- Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) Change From Baseline(Baseline and Week 26)