A 12-Month, Open-Label Safety Study of Simufilam Followed by a 6-Month Randomized Withdrawal and 6 Additional Months Open-Label in Mild-to-moderate Alzheimer's Disease Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 220
- 试验地点
- 14
- 主要终点
- Safety and Tolerability (Randomize Withdraw Abnormal Vital Signs)
研究概览
简要总结
A two-year safety study of simufilam (PTI-125) 100 mg oral tablets twice daily for participants of the previous simufilam studies as wells as additional new mild-to-moderate Alzheimer's disease subjects for a total of 200 participants. All participants will receive simufilam 100 mg tablets twice daily for one year, followed by a 6-month randomized, double-blind period where subjects will either continue on active treatment or be switched to placebo. The study concludes with an additional 6-month open-label treatment period. Clinic visits are every month or month and a half in the first year, and every 3 months in the second year with an additional visit at Month 13. Cognition and neuropsychiatric symptoms are evaluated.
详细描述
The objectives of this study are to build the safety database for simufilam (PTI-125) and to investigate its effects on biomarkers, cognition and neuropsychiatric symptoms during 12-month twice-daily administration in mild-to-moderate AD patients. Additional objectives are to assess differences in cognition and neuropsychiatric symptoms between active and placebo arms in the 6-month randomized period. All subjects will undergo lumbar puncture at screening for baseline testing of cerebrospinal fluid (CSF) total tau and Abeta42, and the first 50 subjects will also provide a CSF sample at Month 6 or Month 12 for evaluation of change from baseline in CSF biomarkers. CSF will not be required of subjects with prior CSF, PET or MRI evidence of Alzheimer's disease. Plasma biomarkers will be evaluated in all subjects. Safety will be assessed by blood tests, electrocardiograms, adverse event monitoring and, at Months 12 and 24, full physical examinations.
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
Matching placebo for the 6-month randomized period (Month 12 to Month 18)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Simufilam 100 mg oral tablets throughout
Simufilam 100 mg oral tablets administered twice daily (BID) for the full 24 months (including the randomized period Month 12 to Month 18)
干预措施: Simufilam 100 mg oral tablet (Drug)
Simufilam 100 mg oral tablets / Placebo / Simufilam 100 mg oral tablets
This placebo arm is only for Month 12 to Month 18. Day 1 to Month 12, as well as Month 18 to Month 24 are open-label treatment periods of simufilam 100 mg b.i.d. for all subjects.
干预措施: Simufilam 100 mg oral tablet (Drug)
Simufilam 100 mg oral tablets / Placebo / Simufilam 100 mg oral tablets
This placebo arm is only for Month 12 to Month 18. Day 1 to Month 12, as well as Month 18 to Month 24 are open-label treatment periods of simufilam 100 mg b.i.d. for all subjects.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and Tolerability (Randomize Withdraw Abnormal Vital Signs)
时间窗: Month 12 to month 18
The most frequently reported Treatment Emergent Adverse Event indicative of abnormal vital signs (hypotension) of simufilam (PTI-125) or placebo during the randomized withdraw portion of the study : Month 12 to Month 18
Change From Baseline in ADAS-Cog-11
时间窗: Day 1 to Month 24
Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item: Change from baseline in cognition over the course of 24 months Possible range in score: 0-70; Subscales are summed; Higher values represent a more cognitively impaired participant Decrease in mean value represents improvement in cognition from one timepoint to the next.
Change From Baseline in ADAS-Cog-11 (Month 12 to Month 24)
时间窗: Month 12 to Month 24
Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item: Change from baseline in cognition Starting at month 12 through month 24; Possible range in score: 0-70; Higher values represent a more cognitively impaired participant; Decrease in mean value represents improvement in cognition from one timepoint to the next.
Safety and Tolerability (Open Label Abnormal Vital Signs)
时间窗: Day 1 to Month 12 and month 18 to month 24
The most frequently reported Treatment Emergent Adverse Events indicative of abnormal vital signs (hypertension/worsening of hypertension and blood pressure increase) of simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)
Safety and Tolerability (Open Label Electrocardiogram Results)
时间窗: Day 1 to Month 12 and month 18 to month 24
The number of subjects that had Treatment Emergent Adverse Events indicative of abnormal Electrocardiogram results while on simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)
Safety and Tolerability (Randomize Withdraw Electrocardiogram Results)
时间窗: Month 12 to Month 18
The number of subjects that had Treatment Emergent Adverse Events indicative of abnormal Electrocardiogram results while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18
Safety and Tolerability (Open Label Abnormal Physical Examination)
时间窗: Day 1 to Month 12 and month 18 to month 24
The most frequently reported Treatment Emergent Adverse Events indicative of abnormal physical examination (weight increase or weight decrease) while administered simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)
Safety and Tolerability (Randomize Withdraw Abnormal Physical Examination Findings)
时间窗: Month 12 to Month 18
The number of subjects that had Treatment Emergent Adverse Events of indicative of abnormal physical examination while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18
Safety and Tolerability (Open Label Abnormal Clinical Laboratory Results)
时间窗: Day 1 to Month 12 and month 18 to month 24
Treatment Emergent Adverse Events when three or more subjects reported abnormal clinical laboratory results while on simufilam (PTI-125) during the open label portion of the study: Open-label period 1 (Day 1 to Month 12) and open-label period 2 (Month 18 to Month 24)
Safety and Tolerability (Randomize Withdraw Abnormal Clinical Laboratory Results)
时间窗: Month 12 to Month 18
Treatment Emergent Adverse Events when two or more subjects reported abnormal clinical laboratory results while on simufilam (PTI-125) or placebo during the randomized withdraw portion of the study: Month 12 to Month 18
次要结局
- Change From Baseline to Month 12 in Cerebral Spinal Fluid for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Mean Concentration (pg/mL)(Day 1 to Month 12)
- Change From Baseline to Month 12 in Cerebral Spinal Fluid for Tau Protein Mean Concentration (pg/mL)(Day 1 to Month 12)
- Change From Baseline to Month 12 in Cerebral Spinal Fluid for Neurogranin Mean Concentration (pg/mL)(Day 1 to Month 12)
- Change From Baseline to Month 12 in Cerebral Spinal Fluid for Neurofilament Light Chain Protein Mean Concentration (pg/mL)(Day 1 to Month 12)
- Change From Baseline to Month 12 in Cerebral Spinal Fluid for Glial Fibrillary Acidic Protein Mean Concentration (pg/mL)(Day 1 to Month 12)