A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects With Amyotrophic Lateral Sclerosis (ALS) With Superoxide Dismutase Type 1 (SOD1) Gene Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 3
- 主要终点
- Adverse Events(AEs)
研究概览
简要总结
This is a Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RAG-17 in Subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation
详细描述
The study is a phase 1, randomized, double-blind, placebo controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RAG-17 in patients with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) gene mutation. The dose levels will be evaluated sequentially across separate cohorts using a rules-based design, wherein participants will receive RAG-17 or placebo at a ratio of 3:1.
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
- •Voluntarily consents to participate in this study and provides written informed consent prior to the start of any study specific procedures.
- •≥ 18 years of age at the time of informed consent.
- •Diagnosis of possible, laboratory supported probable, probable, or definite ALS according to the World Federation of Neurology El Escorial.
- •Documented SOD1 mutation.
- •Forced vital capacity (FVC) ≥50% of predicted value as adjusted for sex, age, and height (measured seated).
- •If taking riluzole or edaravone, subject must be on a stable dose or ≥30 days prior to Day 1 and expected to remain at that dose until the final study visit.
排除标准
- •Documented p.F21C SOD1 mutation.
- •Treatment with another investigational drug, biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering ribonucleic acid, stem cell therapy, or gene therapy is allowed.
- •Current enrollment in any other interventional study.
- •History of or positive test result for human immunodeficiency virus, hepatitis C virus antibody or hepatitis B virus.
- •Pregnant or currently breastfeeding.
研究组 & 干预措施
RAG-17
RAG-17 is administered by intrathecal injection to subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation
干预措施: RAG-17 (Drug)
Placebo
Placebo is administered by intrathecal injection to subjects with Amyotrophic Lateral Sclerosis (ALS) with Superoxide Dismutase Type 1 (SOD1) Gene Mutation
干预措施: Placebo (Drug)
结局指标
主要结局
Adverse Events(AEs)
时间窗: Before treatment and within 57 days after treatment
Assesment of Safety and Tolerability: Incidence and severity of treatment-emergent Adverse Events(AEs) and Serious Adverse Events(SAEs)
次要结局
- Plasma Pharmacokinetic (PK) Parameter: AUC0-last(Before treatment and within 48 hours after treatment)
- Plasma Pharmacokinetic (PK) Parameter: Cmax(Before treatment and within 48 hours after treatment)
- Plasma Pharmacokinetic (PK) Parameter: λz(Before treatment and within 48 hours after treatment)
- Plasma Pharmacokinetic (PK) Parameter: T½(Before treatment and within 48 hours after treatment)
- Plasma Pharmacokinetic (PK) Parameter: Vz/F(Before treatment and within 48 hours after treatment)
- Plasma Pharmacokinetic (PK) Parameter: MRT(Before treatment and within 48 hours after treatment)
- CSF Pharmacokinetic (PK) Parameter: Concentration(Before treatment and within 29 days after treatment)
- Plasma Pharmacokinetic (PK) Parameter: CL/F(Before treatment and within 48 hours after treatment)
- Plasma Pharmacokinetic (PK) Parameter: AUC0-inf(Before treatment and within 48 hours after treatment)
- Plasma Pharmacokinetic (PK) Parameter: Tmax(Before treatment and within 48 hours after treatment)
- CSF Pharmacokinetic (PK) Parameter: T½(Before treatment and within 29 days after treatment)