A Phase 1/2, Multicenter, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Exploratory Efficacy of Intrathecally Administered Gene Therapy AMT-162 in Adult Participants With SOD1 Amyotrophic Lateral Sclerosis (SOD1-ALS).
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 20
- 试验地点
- 12
- 主要终点
- To evaluate the safety and tolerability of ascending doses of intrathecally administered AMT-162 in Participants with SOD1-ALS
研究概览
简要总结
This is the study of AMT-162 in Participants with SOD1-ALS and is designed to evaluate the safety, tolerability, and exploratory efficacy of intrathecally administered gene therapy AMT-162. AMT-162-001 is a Phase 1/2, multi-center, single ascending dose study.
详细描述
AMT-162 is an investigational gene therapy that encodes an artificial microribonucleic acid (microRNA or miRNA) targeting the SOD1 gene. This clinical study will test the safety of AMT-162 and explore the hypothesis that it will silence expression of mutant cytosolic SOD1 and thereby ameliorate the course of ALS caused by this mutant gene.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Confirmed clinical and genetic diagnosis of SOD1-mediated ALS (SOD1-ALS) experiencing signs and/or symptoms of lower motor neuron dysfunction (weakness, atrophy, cramps, fasciculations), with or without upper motor neuron symptoms (weakness, bring reflexes, spasticity).
- •ALSFRS-R score ≥ 25 at Screening.
- •Slow vital capacity (SVC) ≥50% of predicted normal value.
- •Capable of providing informed consent and complying with trial procedures, including: medically able to undergo lumbar puncture and has a responsible caregiver able to attend all clinic visit with the Participant.
排除标准
- •SOD1 pathogenic or likely pathogenic variants in amino acid regions 43-
- •Pathogenic repeat expansion in the C9orf72 gene
- •Any of the following prior or concomitant treatments:
- •Any prior SOD1 suppression therapy with viral microRNA mediators
- •Prior SOD suppression therapy with antisense oligonucleotide (ASO) mediators such as tofersen (QALSODY™). Exception: Patients who previously received tofersen may be enrolled if the last dose of tofersen was received at least 20 weeks prior to the first Screening assessment and if there were no previous tofersen-related SAEs or ongoing tofersen-related adverse events that would increase the risk of receiving AMT-162, per Investigator judgment.
- •Other ALS medications riluzole (RILUTEK®, TIGLUTIK®), edaravone (RADICAVA®), and sodium phenylbutyrate and taururosdiol combination (RELYVRIO) or bioequivalents are allowed if dose is stable for 30 days prior to immunosuppression.
- •Any prior administration of an AAV gene therapy.
研究组 & 干预措施
3 single Ascending Dose Levels
Experimental: 3 single Ascending Dose Levels
The study will be open-label with an initial plan to explore 3 dose levels of AMT-162 in approximately 6 to 12 Participants in total. Each Participant will receive a single dose of AMT-162 delivered via an intrathecal (IT) infusion and will be followed for up to 5 years after AMT-162 administration.
干预措施: AMT-162 (Drug)
EXPANSION COHORT
Expansion cohort: To further test selected dose from the SAD part in approximately 6 to 8 participants
The study will be open-label. Each Participant will receive a single dose of AMT-162 delivered via an intrathecal (IT) infusion and will be followed for up to 5 years after AMT-162 administration.
干预措施: AMT-162 (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of ascending doses of intrathecally administered AMT-162 in Participants with SOD1-ALS
时间窗: up to 5 years
Occurrence of TEAEs upon administration of ascending doses of AMT-162
次要结局
- Characterization of the Effect of intrathecally administered AMT-162(up to 5 years)
- Characterization of Immune Response to AMT-162 and Shedding of intrathecally administered AMT-162.(up to 5 years)