A Multicenter, Randomized, Double-blind, Placebo-controlled, Parellel-group Study to Assess the Efficacy and Safety of MLC901 (NeuroAiD™II) in Subjects With Mild to Moderate Alzheimer's Disease (AD).
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Alzheimer's Disease Assessment Scale-Cognitive Subscale14 (ADAS-Cog14)
研究概览
简要总结
ATHENE II is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial designed to evaluate the efficacy and safety of MLC901 in subjects with mild to moderate Alzheimer's disease, as well as its effects on plasma biomarkers compared to placebo.
详细描述
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatments that slow progression. Current symptomatic therapies provide modest benefit, while anti-amyloid agents target a single pathway and have uncertain long-term outcomes. Multitarget approaches may provide broader and more durable benefit. MLC901 (NeuroAiD™II), a Traditional Chinese Medicine derived formulation, has shown neuroprotective and neuroproliferative properties in preclinical studies through multimodal mechanisms, including modulation of amyloid beta and tau phosphorylation, reduction of oxidative stress and inflammation, and promotion of neurogenesis and synaptogenesis. Clinical studies, including the ATHENE trial, suggest MLC901 may slow cognitive decline and is well tolerated. ATHENE II is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolling approximately 350 patients with mild to moderate AD across Southeast Asia. Participants will receive MLC901 or placebo for 12 months. The primary objective is to determine whether MLC901 is superior to placebo in slowing cognitive decline as measured by ADAS-Cog11. Secondary and exploratory objectives include global cognition, function, behavior, safety, and plasma biomarkers of AD (p-tau217, NfL and GFAP).
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)
盲法说明
Study partner and sponsor
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
- •Male or female subjects aged ≥ 50 years at the time of providing informed consent.
- •Diagnosis of AD based on the National Institute on Ageing and the Alzheimer's Association (NIA-AA) criteria, supported by the presence of a Core 1 AD biomarker, specifically elevated plasma ptau217 ≥0.471 pg/mL.
- •MMSE score between 10 and 26, inclusive, at baseline, corresponding to mild to moderate AD.
- •Subjects may be either treatment-naïve or currently receiving stable symptomatic treatment for AD for at least the 2 months prior to screening, including AChEIs, memantine, or a combination of both.
- •Subjects must have a designated study partner who provides ongoing support during the study and interacts with the subject for a minimum of 8 hours per week, and will accompany the subject to study visits or be available by telephone at designated times.
- •A second study partner may serve as backup. If the original study partner withdraws from participation, a replacement study partner may be permitted at the investigator's discretion. The replacement study partner must provide informed consent prior to their first study visit with the subject.
- •Both the subject (or their legally authorized representative) and the study partner(s) must be capable of providing informed consent.
- •Subjects must have adequate literacy, vision, and hearing, in the opinion of the investigator at the time of screening, to allow for valid administration of the clinical outcome assessments.
排除标准
- •Presence of any neurological disorder contributing to cognitive impairment other than AD, including but not limited to: Parkinson's disease, Dementia with Lewy bodies, and epilepsy or recurrent seizures.
- •Evidence of other clinically significant cerebrovascular disease or intracranial abnormalities based on the latest brain CT or MRI, including but not limited to: multiple lacunar infarcts, large territorial infarcts, severe small vessel or white matter disease, normal pressure hydrocephalus, space occupying lesions.
- •The most recent available scan (obtained at diagnosis or subsequently) is usually sufficient for screening eligibility to exclude these other conditions. Repeat imaging may need in some cases to be considered if there is clinically significant deterioration or new neurological signs suggestive of a cerebrovascular event.
- •Presence of any serious or unstable medical illnesses, including but not limited to: cardiovascular, respiratory, gastroenterological, endocrinologic, immunologic, hematologic, hepatic, or renal and other conditions, that, in the investigator's judgment, may interfere with study participation or compromise subject safety.
- •Patients with a CDR Global Score of 0, 0.5 or 3 at the Screening Phase, corresponding to no, very mild or severe dementia, respectively, will be excluded from the study.
- •Severe visual or hearing impairment that would prevent the subject from accurately completing clinical outcome assessments.
- •Serum creatinine > 130 µmol/L at baseline, which may affect plasma biomarker analysis.
- •Female subjects who are pregnant at screening.
- •Participation in another clinical trial or receipt of any investigational product within 60 days or 5 half-lives (whichever is longer) prior to screening.
- •Current use at baseline of any AD disease modifying therapies including anti-amyloid therapy or neuroprotective/nootropic agents, including Ginkgo biloba, Neurotain, Citicoline, Cerebrolysin, or Piracetam.
- •Known hypersensitivity or allergic reaction to MLC901 or any of its components. Any known food allergy or hypersensitivity to Astragalus membranaceus, Ligusticum chuanxiong, Polygala tenuifolia, Angelica sinensis or members of the Fabaceae/Leguminosae family (e.g., legume, pea, bean), Polygalaceae family (e.g., milkwort, snakeroot), Apiaceae/Umbelliferae family (e.g., anise, caraway, carrot, celery, dill, parsley, parsnip) or Quillaja bark (soapbark).
研究组 & 干预措施
MLC901
Active arm
干预措施: MLC 901 (Drug)
Placebo
Matching placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Alzheimer's Disease Assessment Scale-Cognitive Subscale14 (ADAS-Cog14)
时间窗: Baseline, Month 3, Month 6, Month 9 and Month 12
The ADAS-Cog is a rater-administered instrument designed to assess the severity of cognitive impairment and associated non-cognitive behaviors characteristic of individuals with AD. It is the most widely used cognitive scale in clinical trials evaluating treatments for mild to moderate AD. For this study, the version of ADAS-Cog14 will be used as the primary efficacy assessment. The ADAS-Cog14 consists of 14 items assessing key areas of cognitive function that are commonly impaired in AD, including: orientation, word recall, word recognition, remembering word recognition test instructions, commands, comprehension of spoken language, naming, word-finding difficulty, spoken language ability, construction praxis, ideational praxis, delayed word recall, number cancellation and maze completion measures. The ADAS-Cog14 total score ranges from 0 to 90, with higher scores indicating greater cognitive impairment.
次要结局
- Clinical Dementia Rating (CDR): Global Score and Sum of Boxes (CDR-SB)(Baseline, Month 6 and Month 12)
- Mini-Mental State Examination (MMSE)(Baseline, Month 3, Month 6, Month 9 and Month 12)
- Montreal Cognitive Assessment (MoCA)(Baseline, Month 3, Month 6, Month 9 and Month 12)
- Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)(Baseline, Month 6 and Month 12)
- Neuropsychiatric Inventory (NPI)(Baseline, Month 6 and Month 12)
- Adverse events(Up to 52 weeks)