A Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients With Early Alzheimer's Disease With Biomarkers of Inflammation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 207
- 试验地点
- 42
- 主要终点
- Change in Early and Mild Alzheimer's Cognitive Composite (EMACC)
研究概览
简要总结
The goal of this Phase 2 Alzheimer's study is to determine whether 1.0 mg/kg XPro1595 confers a benefit on cognition, function, and biomarkers of white matter and to further evaluate safety and tolerability. The objectives of this study are to determine the safety, tolerability, and efficacy of XPro1595 in patients with early ADi.
详细描述
This trial is a randomized clinical study using XPro1595 to treat patients with Early Alzheimer's Disease with biomarkers of inflammation (ADi). Early ADi patients are defined as patients with Mild Alzheimer's Disease or Mild Cognitive Impairment (MCI) with a biomarker of inflammation.
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
- •The screening window for this trial is 45 days.
- •Inclusion Criteria:
- •To be eligible for study entry, patients must satisfy all of the following criteria:
- •Adult patients 50 years to ≤ 85 years of age at the time of consent;
- •Meets the diagnostic criteria of MCI of probable Alzheimer's disease (Jack et al. 2018; NIA-AA) or mild dementia as clinically described in McKhann, (2011) and corresponding to stages 3 or 4 of the revised AD staging system (Jack, 2018). (NIA-AA);
- •Amyloid positive (documented in medical history or assessed during screening through blood test);
- •Either currently or previously (in pre-AD condition) literate and capable of reading, writing, and communicating effectively with others;
- •Residence in an assisted living is allowed as is personal assistances provided in the home, however at time of enrollment participant must be able to perform most ADL with minimal assistance, and participant must be permitted sufficient independence to allow assessment of change in ADL;
- •Has a study partner for the duration of the trial who either lives in the same household or interacts with the patient at least 4 hours per day and on at least 4 days per week, who is knowledgeable about the patient's daytime and night-time behaviors and who can be available to attend all clinic visits in person at which caregiver assessments are performed.
排除标准
- •Patients will be excluded from the study if 1 or more of the following criteria are applicable:
- •Have any contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (e.g., in-skull and cardiac devices other than those approved as safe for use in MRI scanners);
- •Receives considerable help to carry out basic ADL living either in the home or as a resident in a nursing home or similar facility;
- •Lifetime history of a major psychiatric disorder including schizophrenia and bipolar disorder. Major depressive disorder that has resulted in 2 or more hospitalizations in a lifetime. Major depressive episode during the past 5 years that is judged by the clinical team unlikely to have been part of Alzheimer's prodrome. History of suicidality.
- •History of substance abuse within 12 months; use of cannabis or cannabis products within 6 months of consent;
- •Enrolled in another clinical trial where patients receive treatment with an investigational drug or treatment device or have had previous treatment with any investigational medicinal product within 60 days or 5 half-lives (whichever is longer) prior to study drug treatment;
- •A prior organ or stem cell transplant;
- •Seated blood pressure of ≥ 165/105 mmHg at Screening.
研究组 & 干预措施
1.0 mg/kg XPro1595
1.0 mg/kg of XPro1595 will be administered via subcutaneous injection once a week for 23 weeks.
干预措施: XPro1595 (Drug)
1.0 mg/kg Placebo
1.0 mg/kg of Placebo will be administered via subcutaneous injection once a week for 23 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Early and Mild Alzheimer's Cognitive Composite (EMACC)
时间窗: 24 Weeks
Change from Baseline to Week 24 in the Early and Mild Alzheimer's Cognitive Composite (EMACC), a z-score composite of six neuropsychological tests (International Shopping List Test-Immediate Recall; Digit Span Forward/Backward; Category Fluency; Letter Fluency \[D-KEFS\]; Trail Making Test A and B; Digit Symbol Coding). Each component is standardized to the pooled baseline mean (0) and SD (1), then averaged. Higher scores indicate better cognitive performance; a positive change from baseline indicates improvement.
次要结局
- Change in apparent fiber density (AFD)(24 Weeks)
- Change in Clinical Dementia Rating (CDR)(24 Weeks)
- Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-MCI-ADL)(24 Weeks)
- Change in myelin content(24 Weeks)
- Change in non-cognitive behavioral symptoms(24 Weeks)
- Change in gray matter integrity(24 Weeks)
- Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)(24 Weeks)
- Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)(24 Weeks)
- Change in brain structure neurodegeneration(24 Weeks)
- Number of participants who experience adverse events and serious adverse events(Baseline up to 28 days post last dose)
- Change in Everyday Cognition (E-Cog)(24 Weeks)
- Change in CDR-SB(24 Weeks)
- Change in Neuropsychiatric Inventory (NPI-12) Total Score at Week 24(24 Weeks)