Ozanimod for the Treatment of Alzheimer's Disease: a Proof-of-concept Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Mean Absolute Change From Baseline in Brain Amyloid Plaque on 18F-florbetaben PET Scan on Ozanimod Group Versus Control Group
研究概览
简要总结
The purpose of this study is to investigate the benefits of ozanimod in patients with moderate Alzheimer's disease.
详细描述
This study will enroll 40 patients with moderate Alzheimer's disease (AD), who will be divided into two groups according to a fixed 1:1 (ozanimod : control) schedule. Patients in control group will receive ongoing approved AD treatment (eg, acetylcholinesterase inhibitors, memantine, or both), while those in the ozanimod group will receive the same approved AD treatment with the addition of ozanimod. The treatment will be for 27 weeks. All participants will undergo assessments at baseline and week 27, including 18F-florbetaben PET imaging, blood tests, and cognitive evaluations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must meet the 2024 diagnostic criteria for Alzheimer's disease (AD) published by the Alzheimer's Association (AA), and be in the moderate stage of AD.
- •The Clinical Dementia Rating-Sum of Boxes (CDR-SB) score must be between 9.5 and 15.
- •Aged 55-80 years.
- •Must be receiving treatment with stable doses of acetylcholinesterase inhibitors, memantine, or both for at least 3 months prior to the screening visit.
- •Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to study visits or be available by telephone at designated times.
- •Have adequate literacy, vision, and hearing for neuropsychological testing in the opinion of the investigator at the time of screening.
排除标准
- •Has diagnosis of a clinically relevant central nervous system (CNS) disease other than AD dementia or other condition that negatively impacts cognition or cognitive status chronically.
- •Contraindications to MRI (e.g., metal implants) or inability to tolerate/comply with the scanning procedure.
- •Prior exposure to ozanimod or any other sphingosine-1-phosphate receptor regulators for AD before starting treatment with ozanimod subject of this study
- •Participants must not have clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, renal, infectious diseases, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the participant at risk by participating in the study in the opinion of the Investigator.
- •Specific cardiac conditions are excluded, including history or presence of:
- •i) Recent (within the past 6 months) occurrence of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, New York Heart Association (NYHA) Class III/IV heart failure, or severe untreated sleep apnea.
- •ii) Resting heart rate <55 beats per minute, second-degree (Mobitz type II) atrioventricular (AV) block, third-degree AV block, sick sinus syndrome, or sino-atrial block unless participants have a pacemaker in place.
- •iii) Prolonged corrected QT interval by Fredericia's formula (QTcF; > 450 msec males and > 470 msec females), or participants at additional risk for QT prolongation.
- •Participants must not receive a live vaccine or a live-attenuated vaccine within 4 weeks prior to first dose or planning to receive a live vaccine or a live-attenuated vaccine during the study or within 90 days after discontinuation from study intervention.
- •Participants must not have a history of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
研究组 & 干预措施
Control Group
Patients will receive ongoing approved AD treatment (eg, acetylcholinesterase inhibitors, memantine, or both).
干预措施: Conventional medication (Drug)
Ozanimod Group
Patients will receive ongoing approved AD treatment (eg, acetylcholinesterase inhibitors, memantine, or both) plus ozanimod. Ozanimod will be administered in strict accordance with the stepwise dose-escalation protocol (Days 1-4: 0.23 mg/day; Days 5-7: 0.46 mg/day), followed by a maintenance dose of 0.92 mg once daily from Day 8. The total treatment duration will be 27 weeks, including both titration and maintenance phases.
干预措施: Ozanimod (Drug)
结局指标
主要结局
Mean Absolute Change From Baseline in Brain Amyloid Plaque on 18F-florbetaben PET Scan on Ozanimod Group Versus Control Group
时间窗: Baseline to Week 27
18F-florbetaben PET imaging was used as a quantitative amyloid biomarker. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in cortical areas of the brain relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a Centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. A negative change indicates an improvement from baseline.
Changes in serum GFAP
时间窗: Baseline to Week 27
We will quantify neuroinflammatory burden through plasma glial fibrillary acidic protein (GFAP) levels, comparing pre- and post-Ozanimod treatment, as well as between the Ozanimod group and the control group. Assessments will be conducted at baseline and week 27.
次要结局
未报告次要终点
研究者
ChenXiaoChun
Professor
Fujian Medical University Union Hospital