A Phase 2a Study of TPN-101 in Patients With Amyotrophic Lateral Sclerosis (ALS) and/or Frontotemporal Dementia (FTD) Associated With Hexanucleotide Repeat Expansion in the C9orf72 Gene (C9ORF72 ALS/FTD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 35
- 主要终点
- Assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD)
研究概览
简要总结
This is a Phase 2a study to assess the the safety and tolerability of TPN-101 in patients with Amyotrophic Lateral Sclerosis (ALS) and/or Frontotemporal Dementia (FTD) Associated with Hexanucleotide Repeat Expansion in the C9orf72 gene (C9ORF72 ALS/FTD).
详细描述
This is a Phase 2a multi-center, randomized, double-blind, placebo-controlled parallel-group, 2-arm study with a long-term, open-label treatment phase in patients with C9ORF72 ALS and/or FTD. This study includes a 6-week Screening Period, a 24-week Double-blind Treatment Period, a 24-week Open-label Treatment Period, and a Follow-up Visit 4 weeks post-treatment.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documentation of a clinical genetic test demonstrating a hexanucleotide repeat expansion (HRE) in the C9orf72 gene
- •Has a reliable caregiver/informant to accompany the patient to all study visits
- •For patients with ALS (with or without FTD):
- •Diagnosis of ALS (probable, possible, laboratory-supported probable or definite) according to the World Federation of Neurology revised E1 Escorial criteria
- •Onset of weakness within 3 years prior to Screening
- •Slow vital capacity (SVC) ≥ 60% of predicted normal adjusted for sex, age, and height (from the sitting position)
- •Able to perform reproducible pulmonary function tests.
- •ALS Functional Rating Scale-Revised (ALSFRS-R) ≥ 30 and score of 3 or 4 on Item #3 (swallowing) at Screening
- •For patients with FTD:
- •A gradual, progressive decline in behavior, language, or motor function consistent with mild cognitive impairment, mild behavioral impairment, mild cognitive/behavioral impairment, behavioral variant FTD, primary progressive aphasia, or amnestic syndrome
- •CDR Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD) global score of 0.5-2.0 at Screening
排除标准
- •Presence of other significant neurological or psychiatric disorders
- •History of clinically significant brain abnormality
- •Clinically significant medical illness
- •Tracheostomy or diaphragmatic pacing
- •Autoimmune disease requiring treatment or management (quiescent rheumatoid arthritis, psoriasis, or controlled Type 1 diabetes are acceptable)
- •History of human immunodeficiency virus (HIV) or hepatitis B infection, or any active infection during Screening, unless the patient will have been symptom-free for at least 30 days prior to randomization
研究组 & 干预措施
TPN-101, 400 mg/day
干预措施: TPN-101, 400 mg/day (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Assess the safety and tolerability of TPN-101 in patients with C9ORF72 amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD)
时间窗: 48 weeks
Incidence and severity of spontaneously reported treatment-emergent adverse events (TEAEs) associated with TPN-101 v. placebo administered for up to 48 weeks in patients with C9ORF72 ALS/FTD
次要结局
- Assess the pharmacokinetics of TPN-101 as measured by concentrations of TPN-101 in plasma and cerebrospinal fluid (CSF)(48 weeks)
- Assess the pharmacodynamic effect of TPN-101 on neurodegeneration as measured by changes in the levels of CSF and blood neurofilament light (NfL)(48 weeks)
- Assess the clinical effect of TPN-101 as measured by changes in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)(48 weeks)