First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ALN-SOD in Participants With Amyotrophic Lateral Sclerosis and SOD1 Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 54
- 试验地点
- 27
- 主要终点
- Incidence of treatment-emergent adverse event (TEAEs) in participants treated with ALN-SOD
研究概览
简要总结
This study is researching an experimental drug called ALN-SOD (called "study drug"). This study is focused on people with Amyotrophic Lateral Sclerosis (ALS) caused by a change in a gene called the Superoxide Dismutase-1 (SOD1) gene. This type of ALS is known as "SOD1-ALS". This is the first time that ALN-SOD will be given to people.
The aim of the study is to see how safe and tolerable the study drug is.
The study is looking at several other research questions, including:
- The effect the study drug has on specific biomarkers, which are substances in the blood or in the fluid that surrounds the brain and spinal cord, known as Cerebrospinal Fluid (CSF)
- How much study drug is in the blood and in the CSF, at different times
- Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
- What effects the study drug has on ALS symptoms
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Phase 1b: Dose Escalation - Double-blind, randomized, and single crossover Phase 2: Cohort Expansion - Open-label
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
- •Weakness attributable to ALS and a SOD1 variant that has been previously described as associated with ALS or is considered likely to cause ALS, as defined in the protocol
- •Slow Vital Capacity (SVC) ≥50% predicted value based on age, gender and height, measured in upright position
- •Body Mass Index (BMI) ≤35 kg/m2 at time of screening
- •If participants are taking riluzole or edaravone, they must be on a stable dose for at least 4 weeks prior to initial dosing visit and are expected to remain at that dose until the end of the study
- •Platelet count >50,000/microliter
- •Has normal blood pressure readings, as defined in the protocol
排除标准
- •Concurrent participation in another interventional clinical trial
- •Has had a tracheostomy
- •Has dementia, as assessed by the investigator
- •Has uncontrolled psychiatric disease, including psychosis, active or recent suicidal ideation, untreated major depression, in the past 30 days
- •Has a medical history of brain or spinal disease/injury that would interfere with the Lumbar Puncture (LP) process, CSF circulation or safety assessment, as defined in the protocol
- •Presence of an implanted shunt for the drainage of CSF or an implanted Central Nervous System (CNS) catheter
- •Presents any concern to the study investigator that might confound the results of the study or poses an additional risk to the participant by their participation in the study
- •Was hospitalized (ie, >24 hours) for any reason other than ALS within 30 days of screening
- •Has received treatment with tofersen within 6 months prior to screening
- •NOTE: Other protocol defined inclusion / exclusion criteria apply
研究组 & 干预措施
Cohort 5 (Optional) - ≤ Dose Level 5
Placebo during 4-Week double-blind treatment period
干预措施: Diluent (Other)
Cohort 5 (Optional) - ≤ Dose Level 5
Placebo during 4-Week double-blind treatment period
干预措施: Placebo (PB) (Drug)
Cohort 2 - Dose Level 2
Placebo during 4-Week double-blind treatment period
干预措施: Diluent (Other)
Cohort 2 - Dose Level 2
Placebo during 4-Week double-blind treatment period
干预措施: ALN-SOD (Drug)
Cohort 5 (Optional) - ≤ Dose Level 5
Placebo during 4-Week double-blind treatment period
干预措施: ALN-SOD (Drug)
Cohort 4 - Dose Level 4
Placebo during 4-Week double-blind treatment period
干预措施: ALN-SOD (Drug)
Cohort 2 - Dose Level 2
Placebo during 4-Week double-blind treatment period
干预措施: Placebo (PB) (Drug)
Cohort 3 - Dose Level 3
Placebo during 4-Week double-blind treatment period
干预措施: Diluent (Other)
Cohort 3 - Dose Level 3
Placebo during 4-Week double-blind treatment period
干预措施: Placebo (PB) (Drug)
Cohort 4 - Dose Level 4
Placebo during 4-Week double-blind treatment period
干预措施: Diluent (Other)
Cohort 4 - Dose Level 4
Placebo during 4-Week double-blind treatment period
干预措施: Placebo (PB) (Drug)
Selected Dose Expansion Cohort(s)
Open Label Treatment (OLT) at selected dose levels. EU Participants can only be included in the Dose Expansion portion of study (Phase 2), not in Dose Escalation (Phase 1)
干预措施: ALN-SOD (Drug)
Cohort 1 - Dose Level 1
Placebo during 4-Week double-blind treatment period
干预措施: ALN-SOD (Drug)
Cohort 3 - Dose Level 3
Placebo during 4-Week double-blind treatment period
干预措施: ALN-SOD (Drug)
Cohort 1 - Dose Level 1
Placebo during 4-Week double-blind treatment period
干预措施: Diluent (Other)
Cohort 1 - Dose Level 1
Placebo during 4-Week double-blind treatment period
干预措施: Placebo (PB) (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse event (TEAEs) in participants treated with ALN-SOD
Incidence of treatment-emergent adverse event (TEAEs) in participants treated with ALN-SOD
Severity of TEAEs in participants treated with ALN-SOD
Severity of TEAEs in participants treated with ALN-SOD
次要结局
- Incidence of anti-drug antibodies (ADAs) to ALN-SOD in serum
- Titer of ADAs to ALN-SOD in serum
- Concentration of ALN-SOD in plasma
- Concentration of ALN-SOD in CSF
- Concentration of SOD1 protein in cerebrospinal fluid (CSF)
- Change in concentration of SOD1 protein in CSF
- Concentration of neurofilament light chain (NfL) in plasma
- Change in concentration of NfL in plasma
- Concentration of NfL in CSF
- Change in concentration of NfL in CSF