A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating, Phase 2a Safety, Tolerability, and Pharmacodynamic Study of Two Doses of an Histone Deacetylase Inhibitor (FRM-0334) in Subjects With Prodromal to Moderate Frontotemporal Dementia With Granulin Mutation
试验速览
- 阶段
- 2 期
- 入组人数
- 30
- 试验地点
- 13
- 主要终点
- Evaluate the safety and tolerability of FRM-0334
研究概览
简要总结
The purposes of this study are to investigate the safety, tolerability, and pharmacodynamics of FRM-0334 in subjects with prodromal to moderate frontotemporal dementia with granulin mutation.
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
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ages aged ≥21 and ≤75 years
- •Genotyped positive for a FTD-GRN mutation, and aware of it
- •Prodromal to moderate FTD-GRN
- •Resides in a stable living situation, living at home, senior residential setting, or an institutional setting without the need for continuous (ie, 24-hour) nursing care
- •Proficiency (oral and written) in the language in which study-related documents, including the ICF and standardized tests, will be administered
- •Able to swallow capsules
- •Be in good general health, willing and able to comply with the protocol requirements, and expected to complete the study as designed (in the judgment of the investigator)
排除标准
- •Clinically significant abnormalities on physical examination, medical history, ECG, vital signs, laboratory values, or unstable medical or psychiatric illness
- •Females who are pregnant, breastfeeding, or planning to become pregnant during the study
研究组 & 干预措施
FRM-0334; Arm 1
low dose, Capsule, Once Daily, Day 1 through Day 28
干预措施: FRM-0334 (Drug)
FRM-0334; Arm 2
high dose, Capsule, Once Daily, Day 1 through Day 28
干预措施: FRM-0334 (Drug)
Placebo Comparator; Arm 3
Placebo, Capsule, Once Daily, Day 1 through Day 28
干预措施: Placebo (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of FRM-0334
时间窗: Baseline to Day 28 or Early Termination
* Number and percentage of subjects with AEs * Number and percentage of subjects with SAEs * Number and percentage of subjects who discontinue due to AEs * Number and percentage of subject deaths
Assess the pharmacodynamic (PD) effects of FRM-0334 on the change from baseline in plasma concentrations of progranulin (PGRN) after 28 days
时间窗: Baseline to Day 28 or Early Termination
次要结局
- Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days(Baseline and Day 28)
- Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 days(Day 1 to Day 28 or Early Termination)
- Characterize the CSF concentrations of FRM-0334 and metabolites following once daily dosing for 28 days(Day 1 to Day 28 or Early Termination)