First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene

JRCT ID: jRCT2061240039

Registered date:25/07/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Amyotrophic lateral sclerosis associated with mutation in the SOD1 gene (SOD1-ALS)
• Date of first enrollment: 20/09/2024
• Target sample size: 5
• Countries of recruitment: Canada,Japan,US,Japan,Belgium,Japan,Germany,Japan,Poland,Japan,Australia,Japan,Taiwan,Japan,South Korea,Japan
• Study type: Interventional

Intervention(s)

[Double-blind period (crossover study)]
Subjects will receive one dose each of ALN-SOD and placebo with Intrathecal (IT) injection.

[Open-label period]
Subjects will receive ALN-SOD with IT injection.

Outcome(s)

Primary Outcome

- Incidence of treatment-emergent adverse event (TEAEs) in participants treated with ALN-SOD
- Severity of TEAEs in participants treated with ALN-SOD

Secondary Outcome

- Concentration of SOD1 protein in cerebrospinal fluid (CSF) over time
- Change in concentration of SOD1 protein in CSF over time
- Concentration of neurofilament light chain (NfL) in plasma over time
- Change in concentration of NfL in plasma over time
- Concentration of NfL in CSF over time
- Change in concentration of NfL in CSF over time
- Concentration of ALN-SOD in plasma over time
- Concentration of ALN-SOD in CSF over time
- Incidence of anti-drug antibodies (ADAs) to ALN-SOD in serum over time
- Titer of ADAs to ALN-SOD in serum over time

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Weakness attributable to ALS and a SOD1 mutation that has been previously described as associated with ALS or is considered likely to cause ALS, as defined in the protocol
2. Slow vital capacity (SVC) >=50% predicted value based on age, gender and height, measured in upright position.
3. Body Mass Index (BMI) <=35 kg/m2 at time of screening
4. If participants are taking riluzole, edaravone, or AMX0035, 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.
5. Platelet count >50,000/microliter.
6. Has normal blood pressure readings, as defined in the protocol
7. NOTE: Other protocol defined inclusion criteria apply

Exclude criteria

1. Concurrent participation in another interventional clinical trial
2. Has had a tracheostomy.
3. Has dementia, as assessed by the investigator.
4. Has uncontrolled psychiatric disease, including psychosis, active or recent suicidal ideation, untreated major depression, in the past 30 days.
5. 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
6. Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter
7. 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
8. Was hospitalized (ie, >24 hours) for any reason other than ALS within 30 days of the screening visit
9. NOTE: Other protocol defined exclusion criteria apply

Related Information

• Primary Sponsor: Levy Oren
• Secondary ID(s): NCT06351592,2023-510344-20-00