A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Study Evaluating the Safety and Efficacy of Simufilam 100 mg Tablets in Subjects With Mild-to-Moderate Alzheimer's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 804
- 试验地点
- 87
- 主要终点
- Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)
研究概览
简要总结
A 52-week safety and efficacy study of simufilam (PTI-125) given twice daily to participants with mild-to-moderate Alzheimer's disease (AD) for 52 weeks. Approximately 750 participants will be randomized (1:1) to receive either placebo or 100 mg tablets of simufilam, twice daily, for 52 weeks. Clinic visits will occur 4 weeks after the baseline visit, and then every 12 weeks until the end of the study. The safety of simufilam, and its efficacy in enhancing cognition and slowing cognitive and functional decline will be evaluated.
详细描述
The primary objective of this study is to investigate the safety and efficacy of simufilam (PTI-125) in enhancing cognition and slowing cognitive and functional decline following 52-week, repeat-dose oral administration in participants with mild-to-moderate AD. Secondary objectives include the assessment of simufilam's effect on neuropsychiatric symptoms and caregiver burden. A third objective is to investigate the effect of simufilam treatment on plasma biomarkers. A limited number of research sites will be invited to participate in the pharmacokinetic (PK) and plasma biomarker sub-study. Collection of PK samples will enable an exposure-response analysis. Approximately 100 subjects will participate (50 per group). Plasma samples will be collected during the Screening Visit and again at Weeks 28 and 52. Change from Baseline for plasma biomarkers represent additional secondary endpoints.
Safety will be evaluated by adverse event monitoring, vital signs, clinical labs, and the Columbia Suicide Severity Rating Scale at every visit. Subjects will undergo magnetic resonance imaging (MRI) during screening to ensure entry criteria are met (unless recent MRI confirms entry criteria). Resting electrocardiograms will be conducted at Baseline (Study Day 1) and Weeks 4, 28, and 52. A complete physical and neurological examination will be performed at screening, and brief examinations will be performed at all other visits. Weight will be measured during the Screening Period, at Baseline (Study Day 1), and at all other visits.
An independent Data Safety Monitoring Board (DSMB) will meet periodically to review subject safety assessments and determine if dosing may continue. A charter will be developed with specific guidance for the DSMB.
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
Randomized treatments will be assigned by subject numbers in a randomly generated numeric sequence. Randomization (1:1) will be stratified by low or high Mini-Mental State Exam (MMSE; 16-20 and 21-27).
The randomization code will not be revealed to study subjects, Investigators, clinical staff, study monitors, or the Sponsor until all subjects have completed therapy and the database has been finalized and locked.
入排标准
- 年龄范围
- 50 Years 至 87 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets National Institute on Aging and Alzheimer's Association Research Framework criteria for individuals in clinical Stage 4 or 5 of the Alzheimer's continuum.
- •Evidence for AD pathophysiology, confirmed either prior to or during screening.
- •MMSE score ≥ 16 and ≤ 27 at screening.
- •Clinical Dementia Rating - Global Score must be 0.5, 1 or
- •If receiving background AD medications, the dosing regimen must be stable for at least 12 weeks prior to randomization. Chronic medications for conditions other than AD (such as depression) must be prescribed at a stable dose for at least 4 weeks prior to screening.
- •The subject has not been a cigarette smoker or chewed tobacco for at least 3 years.
- •Availability of a study partner.
- •Individuals who have participated in a clinical study with an investigational drug targeting the underlying AD process may be permitted to participate in this study.
- •Completed a COVID-19 vaccine primary series ("fully vaccinated") at least 2 weeks prior to randomization or had an unambiguous COVID-19 infection diagnosed more than 3 months before the start of the Screening Period.
排除标准
- •A neurologic condition other than AD that significantly contributes to the subject's dementia.
- •Any current primary psychiatric diagnosis other than AD if it is likely to confound cognitive assessment or ability to comply with study procedures.
- •Geriatric Depression Scale (15-item) score >
- •(Note - a subject with a score > 8 may continue in screening if, in the judgment of the Investigator, the elevated score is not attributed to a major depressive episode).
- •Suicidal ideation during the past 3 months or suicidal behavior during the past 12 months.
- •Alcohol or substance use disorder within 2 years of screening.
- •MRI presence of cerebral vascular or other significant pathology.
- •History of transient ischemic attack or stroke within 12 months of screening
- •Seizure within 12 months of screening.
- •Severe head trauma or head trauma considered likely to be contributing to the subject's cognitive impairment.
- •Sleep apnea that is considered likely to be contributing to the subject's cognitive impairment.
- •Insufficiently controlled diabetes mellitus or hypertension.
- •Body mass index < 18.5 or > 37.
- •History or diagnosis of clinically significant cardiac disease
- •Currently or previously prescribed/administered aducanumab, lecanemab, or any anti-amyloid monoclonal antibody, more than 2 doses.
研究组 & 干预措施
Placebo
Matching placebo, supplied by Cassava as coated tablets, and taken twice daily (b.i.d.) for 52 weeks
干预措施: Placebo (Drug)
Simufilam 100 mg
Simufilam 100 mg, supplied by Cassava as coated tablets, and taken b.i.d. for 52 weeks
干预措施: Simufilam (Drug)
结局指标
主要结局
Change From Baseline in the 12-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12)
时间窗: Baseline (Study Day 1) to Week 52
The change from baseline to Week 52 in the ADAS-Cog12, a psychometrician-administered battery comprised of several cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Scores range from 0 (best) to 80 (worst).
Change From Baseline in the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
时间窗: Baseline (Study Day 1) to Week 52
The change from baseline to Week 52 in the ADCS-ADL, a 23-item study partner questionnaire that covers both basic activities of daily living (ADL) and more complex ADL or instrumental ADL. Scores range from 0 to 78, with a lower score indicating greater severity of functional loss.
次要结局
- Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS)(Baseline (Study Day 1) to Week 52)
- Change From Baseline in the Neuropsychiatric Inventory (NPI)(Baseline (Study Day 1) to Week 52)
- Change From Baseline in the Mini-Mental State Exam (MMSE)(Baseline (Study Day 1) to Week 52)
- Change From Baseline in the Clinical Dementia Rating Sum of Boxes (CDR-SB)(Baseline (Study Day 1) to Week 52)
- Change From Baseline in the Zarit Burden Interview (ZBI)(Baseline (Study Day 1) to Week 52)
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