Testing a new drug for ALS caused by SOD1 gene mutations

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

This study is testing a new drug for adults with ALS caused by SOD1 gene mutations to see if it's safe and how it affects their symptoms and certain markers in their blood and spinal fluid.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Regeneron Pharmaceuticals (Industry-sponsored)
• Locations: 16 sites (Concord, New South Wales and 15 other locations)
• Trial ID: NCT06351592 on ClinicalTrials.gov

What this trial studies

This clinical trial is investigating an experimental drug called ALN-SOD in adults with amyotrophic lateral sclerosis (ALS) linked to mutations in the superoxide dismutase-1 (SOD1) gene. It is the first time this drug will be administered to humans, focusing on its safety and tolerability. The study will also evaluate the drug's effects on specific biomarkers in the blood and cerebrospinal fluid, its concentration in these fluids over time, and the body's immune response to the drug. Additionally, the trial aims to assess any changes in ALS symptoms resulting from the treatment.

Who should consider this trial

Good fit: Ideal candidates include adults with ALS due to a known or likely pathogenic SOD1 mutation and specific respiratory function criteria.

Not a fit: Patients with concurrent participation in other clinical trials or those with severe psychiatric conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new therapeutic option for patients with SOD1-ALS.

How similar studies have performed: While this approach is novel in humans, similar studies targeting genetic mutations in ALS have shown promise in preclinical models.

Eligibility criteria

Key Inclusion Criteria:

1. 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
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 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
5. Platelet count \>50,000/microliter
6. Has normal blood pressure readings, as defined in the protocol

Key Exclusion 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 screening
9. Has received treatment with tofersen within 6 months prior to screening

NOTE: Other protocol defined inclusion / exclusion criteria apply

Where this trial is running

Concord, New South Wales and 15 other locations

• Concord Repatriation General Hospital — Concord, New South Wales, Australia (Recruiting)
• Macquarie University — Sydney, New South Wales, Australia (Recruiting)
• Sunshine Coast University Hospital — Birtinya, Queensland, Australia (Recruiting)
• KU Leuven — Leuven, Vlaams-Brabant, Belgium (Recruiting)
• University of Alberta Hospital, Edmonton, Division of Neurology — Edmonton, Alberta, Canada (Recruiting)
• University Hospital - London Health Sciences Centre — London, Ontario, Canada (Recruiting)
• Sunnybrook Research Institute — Toronto, Ontario, Canada (Recruiting)
• Montreal Neurological Institute and Hospital — Montreal, Quebec, Canada (Recruiting)
• Hokkaido University Hospital — Sapporo, Hokkaido, Japan (Recruiting)
• Tokushima University Hospital — Tokushima, Tokushima, Japan (Recruiting)
• Toho University Omori Medical Center — Ōta-ku, Tokyo, Japan (Recruiting)
• Kyoto University Hospital — Kyoto, Japan (Recruiting)
• Hanyang University Seoul Hospital — Seoul, South Korea (Recruiting)
• Seoul National University Hospital — Seoul, South Korea (Recruiting)
• Kaohsiung Chang Gung Memorial Hospital — Kaohsiung City, Taiwan (Recruiting)
• Taipei Veterans General Hospital — Taipei, Taiwan (Recruiting)

Study contacts

• Study coordinator: Clinical Trials Administrator

Conditions Amyotrophic Lateral Sclerosis; Mutation in the Superoxide Dismutase-1 Gene; Symptomatic; Known pathogenic mutation; Predicted pathogenic mutation