A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose Escalation Study of NPT088 in Patients With Probable Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 23
- 主要终点
- Number of patients with adverse events
研究概览
简要总结
The purpose of the study is to evaluate the safety and tolerability of multiple doses of NPT088 in patients with mild to moderate probable Alzheimer's Disease. The study will also evaluate the pharmacokinetics, immunogenicity and exploratory pharmacodynamic characteristics of multiple doses of NPT088.
详细描述
This study is a multicenter Phase 1, randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation safety and tolerability study of NPT088 or placebo in patients with Probable AD with a MMSE score of 16-27. Enrolled patients will receive an intravenous infusion of NPT088 or placebo once a month for six months during this study. Four dose cohorts are planned with the first two cohorts enrolling 9 patients each (6 NPT088: 3 placebo) and the final two cohorts enrolling 24 patients each (16 NPT088: 8 placebo) for a total of 66 patients (44 NPT088: 22 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
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For enrollment in the study, participants must
- •be between 50 and 85 years of age, inclusive
- •have a Mini Mental State Examination (MMSE) scores between 16-27 (inclusive)
- •have a Modified Hachinski Score of less than or equal to 4
- •have a diagnosis of Probable Alzheimer's Disease (AD) according to consensus criteria defined by the National Institute on Aging-Alzheimer's Association work group
- •have a Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0, with the memory box score equal to or greater than 0.5
- •have a positive florbetapir positron emission tomography (PET) amyloid scan
- •consent to apolipoprotein E (ApoE) genotyping
- •be willing to undergo repeat Magnetic Resonance Imaging (MRI) and PET imaging
- •be on stable doses of allowed medications for at least 30 days prior to Screening. Concurrent treatment with cholinesterase inhibitors and/or memantine is allowed
- •be in good healthy apart from the clinical diagnosis of AD
- •have a dedicated Caregiver who provides care at least 4 hours a day for 4 days a week and will provide informed consent for their participation
排除标准
- •For enrollment in the study, participants must NOT:
- •have a history of, or screening MRI indicative of any significant brain abnormality
- •have any major medical illness or unstable medical condition or in the opinion of the Investigator have any reason that may interfere with the participants ability to comply with the study procedures and abide by study restrictions or with the ability to interpret safety data
- •reside in a nursing home or need 24-hour care and supervision
- •take excluded medications
- •have exclusionary values on the Screening blood and urine sample
- •have been treated with immunomodulators to treat AD
- •have participated in an investigational drug or device study within 90 days
- •have a known allergy to study drug
研究组 & 干预措施
Cohort 3
Participants will receive monthly IV infusions of either mid-high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months
干预措施: Placebo (Drug)
Cohort 4
Participants will receive monthly IV infusions of either high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months
干预措施: NPT088 (Drug)
Cohort 1
Participants will receive monthly IV infusions of either low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months
干预措施: NPT088 (Drug)
Cohort 1
Participants will receive monthly IV infusions of either low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months
干预措施: Placebo (Drug)
Cohort 2
Participants will receive monthly IV infusions of either mid-low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months
干预措施: NPT088 (Drug)
Cohort 2
Participants will receive monthly IV infusions of either mid-low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months
干预措施: Placebo (Drug)
Cohort 3
Participants will receive monthly IV infusions of either mid-high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months
干预措施: NPT088 (Drug)
Cohort 4
Participants will receive monthly IV infusions of either high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months
干预措施: Placebo (Drug)
结局指标
主要结局
Number of patients with adverse events
时间窗: Baseline to Week 32
次要结局
- Multiple dose PK CSF concentrations of NPT088(Up to Week 32)
- Multiple dose pharmacokinetic (PK) serum concentrations of NPT088(Up to Week 32)
- Multiple dose immunogenicity of NPT088(Up to Week 32)