A Phase 2, Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients With Mild Cognitive Impairment (MCI) With Biomarkers of Inflammation
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 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 MCI study is to determine whether 1.0 mg/kg XPro1595 is superior to placebo at improving measures of cognition, functioning and brain quality in individuals with MCI and biomarkers associated with neuroinflammation (APOE4) and to evaluate safety, tolerability, and efficacy of XPro1595.
详细描述
This study is designed as a Phase 2, double-blind randomized, placebo-controlled study investigating the safety, tolerability, and efficacy of XPro1595 in patients with MCI. The planned dose is 1.0 mg/kg of XPro1595 and matching 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients are eligible to be included in the study only if all the following criteria apply:
- •Adult male and female patients ≥ 55 years to ≤ 80 years of age at the time of consent;
- •Diagnosed with MCI of probable Alzheimer's disease (Albert 2011; National Institute on Aging - Alzheimer's Association [NIA-AA]). Patients who have received previous therapy for Alzheimer's disease may still be eligible;
- •Amyloid positive (documented in medical history or assessed during screening through blood test);
- •Literate and capable of reading, writing, and communicating effectively with others, based on the PI's assessment;
- •Has a study partner willing to participate 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 informant assessments are performed.
排除标准
- •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 at the strength required for this study);
- •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: has answered "yes" to Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation items 4 or 5, or any suicidal behavior within 6 months before Screening, at Screening, or at the Week 1 Visit, or has been hospitalized or treated for suicidal behavior in the past 5 years before Screening;
- •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 received treatment on another AD clinical trial within the last 60 days from Day 1
研究组 & 干预措施
1.0 mg/kg XPro1595
1.0 mg/kg XPro1595 will be administered via subcutaneous injection once a week for 12 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 12 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: 12 Weeks
Change from Baseline to Week 12 in the Early and Mild Alzheimer's Cognitive Composite (EMACC) (Jaeger 2017) made up of the following tests: * International Shopping List Test- Immediate recall (Word List Learning Test-Immediate recall) * Trail Making Test Part A and B * Digit Symbol Coding Test * Digit Span Forward and Backward * Category Fluency Test (DKEFS) * Letter Fluency Test (DKEFS) To assess the efficacy of XPro1595 compared with placebo on cognitive performance in patients with MCI
次要结局
- Change in myelin content(12 Weeks)
- Change in brain activity(12 Weeks)
- Change in speech and language(12 Weeks)
- Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker amyloid)(12 Weeks)
- Change in Mean Computer-based Cognitive Assessment (Cogstate) Composite score from Screening to Week 12(12 Weeks)
- Change in Imaging (MRI) Neuroinflammation(12 Weeks)
- Change in apparent fiber density (AFD)(12 Weeks)
- Change in blood inflammatory and neurodegeneration biomarkers (on blood inflammatory and neurodegeneration biomarker pTau)(12 Weeks)
- Change in imaging markers of brain quality(12 Weeks)
- Change in non-cognitive behavioral symptoms(12 Weeks)
- Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)(12 Weeks)
- Number of participants who experience adverse events and serious adverse events(Screening up to 28 days post last dose)
- Change in Alzheimer's Disease Cooperative Study - Mild Cognitive Impairment Activities of Daily Living (ADCS-MCI ADL)(12 Weeks)