NCT05633459进行中（未招募）1 期
A Multi-Center, Randomized, Double-Blind Placebo Controlled Multiple-Ascending Dose Study to Evaluate the Safety and Tolerability of QRL-201 in Amyotrophic Lateral Sclerosis, Followed by an Open-Label Extended Dosing Period
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 69
- 试验地点
- 27
- 主要终点
- Number of participants with one or more treatment emergent adverse events and serious adverse events
研究概览
简要总结
The primary objective of this study is to determine the safety and tolerability of multiple doses of QRL-201 in people living with ALS
详细描述
This first-in-human, Phase 1 study will evaluate the safety, tolerability, and pharmacokinetics (PK) of QRL-201 administered intrathecal (IT) to participants with Amyotrophic Lateral Sclerosis. Two dose escalation cohorts of 8 participants each, followed by an additional 48 participants, receiving the study drug in a 6:2 ratio of QRL-201 to placebo.
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)
盲法说明
Multiple-ascending doses of QRL-201 or placebo will be administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(Double-Blind Periods):
- •Male or female participants aged 18 to 80 years diagnosed with ALS
- •ALS symptom onset within 24 months of Screening
- •Slow vital capacity >50%
- •Clinical or electrodiagnostic evidence of lower motor neuron involvement
- •Not pregnant and not nursing
- •Willing and able to practice effective contraception
- •Able to tolerate lumbar puncture
- •If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)
排除标准
- •(Double Blind Periods):
- •Pathogenic variant, likely pathogenic variant, or variant of uncertain significance in the superoxide dismutase 1 (SOD1) and/or fused in sarcoma (FUS) genes
- •Currently enrolled in any other clinical study involving either an investigational product (IP) or off-label use of a drug or device
- •Prior exposure to stem cell or gene therapy products
- •Any contraindication to intrathecal drug administration
- •Abnormal laboratory values deemed clinically significant by the Investigator
- •Significant infection or known inflammatory process
- •Any sign and/or history of neurological conditions and other neuromuscular disorders that could affect the electrophysiological recordings.
- •An EEG that shows signs of abnormal electrical activity (e.g., epilepsy)
- •Inclusion Criteria (Open-Label Extended Dosing Period):
- •Male or female participants in the sporadic ALS and C9orf72 ALS Cohorts of QRL-201-01 who have completed through at least Day 253 of safety follow up in the double-blind study period OR have completed Cohort 1 of Cohort 2
- •Not pregnant and not nursing
- •Willing and able to practice effective contraception
- •Can visit study site for required visits
- •Able to tolerate lumbar puncture
- •If on approved therapies for the treatment of ALS during the course of the study, must be on a stable dose (at the Sponsor's discretion)
- •Exclusion Criteria (Open-Label Extended Dosing Period):
- •Currently enrolled in any other clinical study involving either an investigational product (IP) or off label use of a drug or device
- •Off-label use of drugs or devices that are being used as disease-modifying therapies in ALS
- •Participated in another clinical study within 30 days, or 5 half-lives of the previous investigational product, whichever is greater, prior to the first dose
- •Prior exposure to stem cell or gene therapy products
- •Is not suitable for inclusion in the Open-Label Extended Dosing period of the study, in the opinion of the Investigator
- •An EEG that shows signs of abnormal electrical activity (NOTE: Cohort 1 and Cohort 2 participants only)
研究组 & 干预措施
QRL-201: C9orf72-ALS
Experimental
QRL-201 will be intrathecally administered to individuals with C9orf72-ALS.
干预措施: QRL-201 (Drug)
QRL-201: Sporadic ALS
Experimental
Multiple-ascending doses of QRL-201 will be intrathecally administered to individuals with ALS.
干预措施: Multiple ascending doses of QRL-201 (Drug)
Placebo: Sporadic ALS
Placebo Comparator
Multiple-ascending doses of placebo comparator will be intrathecally administered to individuals with ALS.
干预措施: Multiple ascending doses of Placebo (Drug)
Placebo: C9orf72-ALS
Placebo Comparator
Placebo comparator will be intrathecally administered to individuals with C9orf72-ALS.
干预措施: Placebo (Drug)
QRL-201: Open-label Extended Dosing Period
Experimental
Open-label QRL-201 will be intrathecally administered to individuals with ALS who qualify for and enter the open-label extended dosing period.
干预措施: QRL-201 (Drug)
结局指标
主要结局
Number of participants with one or more treatment emergent adverse events and serious adverse events
时间窗: Baseline through Day 421 [End of Study Visit
Endpoints: A summary of treatment emergent adverse events, serious adverse events, and other non-serious adverse events, regardless of causality, will be reported in the Reported Adverse Events module.
次要结局
- Pharmacokinetics (plasma): Maximum observed concentration of QRL-201 (Cmax)(Predose up to 24 hours post dose)
- Pharmacokinetics (plasma): Time of maximum concentration (Tmax) of QRL-201(Predose up to 24 hours postdose)
- Pharmacokinetics (plasma): Area under the concentration time curve from zero to infinity (AUCinf) of QRL-201(Predose up to 24 hours post dose)
研究者
研究点 (27)
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