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

Prior treatment

• Concurrent participation in another interventional clinical trial
• Has received treatment with tofersen within 6 months prior to screening
  • NOTE: Other protocol defined inclusion / exclusion criteria apply

Other illness

• 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

Other

• Has had a tracheostomy
• 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

• 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