A Randomized, Double-Blind, Placebo-Controlled, Phase 1 / 2 Trial Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of TRCN-1023 Administered by Intrathecal Injections to Adult People Living With Amyotrophic Lateral Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Frequency of Adverse Events
研究概览
简要总结
The FUNCtion Amyotrophic Lateral Sclerosis (ALS) trial is a randomized, double-blind, placebo-controlled Phase 1/2 trial to evaluate the safety and tolerability of TRCN-1023 in adults living with ALS. TRCN-1023 is an investigational medicine given as a single injection into the fluid surrounding the spine (intrathecal injection). The trial will also assess how the body processes the drug and whether it shows early signs of benefit over 24 weeks.
详细描述
TRCN-1023 is an investigational medicine designed to restore the function of a protein called UNC13A, which becomes disrupted in most people with Amyotrophic Lateral Sclerosis (ALS) due to a breakdown in how nerve cells process genetic information. This trial is designed to evaluate the safety and tolerability of TRCN-1023 given as a single injection into the fluid surrounding the spine, and to identify the best dose to carry forward into future studies. TRCN-1023 stays in the brain and spinal cord long enough that it may only need to be administered once every 24 weeks. The trial will also assess how the body processes the drug, whether it engages its intended target, and its effects on disease progression, physical function, and quality of life.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 to 75 years
- •Diagnosis of ALS (clinically definite, clinically probable, or clinically probable laboratory supported)
- •ALS symptoms began within the past 24 months
- •Able to perform breathing tests: slow vital capacity (SVC) with consistent results, with breathing capacity of at least 60% of the expected value
- •Able and willing to meet all study requirements, including travel to the study site, brain magnetic resonance imaging (MRI) scans, lumbar punctures, and blood draws
- •Able and willing to use wearable sensors and complete speech assessments at home
- •On a stable dose of approved ALS medication for at least 4 weeks prior to screening
- •Capable of providing informed consent
排除标准
- •Carries a confirmed SOD1 or FUS gene mutation
- •Has a tracheostomy or requires continuous assisted ventilation more than 22 hours per day during the preceding 3 months before the first Screening Visit
- •Has a contraindication to brain MRI (e.g., pacemaker, metal implants)
- •Has a contraindication to lumbar puncture or spinal injection (e.g., blood clotting disorders, certain blood thinners, signs of increased pressure in the brain)
- •Has significant abnormal liver, kidney, or blood test results
- •Is currently enrolled in another clinical trial or has received an investigational treatment within the past 4 weeks
- •Has previously received gene therapy, stem cell therapy, or another Antisense oligonucleotide (ASO) treatment
- •Has a clinically significant condition other than ALS that could interfere with study participation
研究组 & 干预措施
TRCN-1023
Antisense oligonucleotide (ASO) administered by intrathecal injection
干预措施: TRCN-1023 (Drug)
Placebo
Matching Placebo Comparator
干预措施: Placebo (Other)
结局指标
主要结局
Frequency of Adverse Events
时间窗: 24 Weeks
Number and frequency of adverse events assessed over 24 weeks following a single intrathecal injection of TRCN-1023 or placebo
次要结局
- Plasma Concentration of TRCN-1023(Day 1 (pre-dose, 1, 2, 6, and 24 hours post-dose), Weeks 4, 10, 16, and 24)
- Cerebrospinal Fluid (CSF) Concentration of TRCN-1023(Day 1 (pre-dose and 24 hours post-dose), Weeks 4, 16, and 24 (up to 4 lumbar punctures post-dose))
- Time to Peak Plasma Concentration (Tmax)(Day 1 (pre-dose, 1, 2, 6, and 24 hours post-dose), Weeks 4, 10, 16, and 24)
- Peak Plasma Concentration (Cmax) of TRCN-1023(Day 1 (pre-dose, 1, 2, 6, and 24 hours post-dose), Weeks 4, 10, 16, and 24)
- Area Under the Plasma Concentration-Time Curve to Last Measurable Concentration (AUClast) of TRCN-1023(Day 1 (pre-dose, 1, 2, 6, and 24 hours post-dose), Weeks 4, 10, 16, and 24)