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

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 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

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis (ALS); Mutation in the Superoxide Dismutase-1 (SOD1) Gene
• Intervention / Treatment: Drug: Placebo (PB); Drug: ALN-SOD; Other: Diluent

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital
    • Sydney, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie University
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Recruiting
      • Sunshine Coast University Hospital
• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • KU Leuven
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2G3
      • Recruiting
      • University of Alberta Hospital, Edmonton, Division of Neurology
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • University Hospital - London Health Sciences Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Research Institute
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Recruiting
      • Montreal Neurological Institute and Hospital
• Japan
  • Kyoto, Japan, 606-8507
    • Recruiting
    • Kyoto University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Recruiting
      • Hokkaido University Hospital
  • Tokushima
    • Tokushima, Tokushima, Japan, 770-0042
      • Recruiting
      • Tokushima University Hospital
  • Tokyo
    • Ōta-ku, Tokyo, Japan, 143-8541
      • Recruiting
      • Toho University Omori Medical Center
• South Korea
  • Seoul, South Korea, 04763
    • Recruiting
    • Hanyang University Seoul Hospital
  • Seoul, South Korea, 3080
    • Recruiting
    • Seoul National University Hospital
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Recruiting
    • Kaohsiung Chang Gung Memorial Hospital
  • Taipei, Taiwan, 11211
    • Recruiting
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - Low; Placebo during 4-Week double-blind treatment period	Drug: Placebo (PB); Administered per the protocol; Drug: ALN-SOD; Administered per the protocol; Other: Diluent; Administered per the protocol
Experimental: Cohort 2 - Mid-Dose; Placebo during 4-Week double-blind treatment period	Drug: Placebo (PB); Administered per the protocol; Drug: ALN-SOD; Administered per the protocol; Other: Diluent; Administered per the protocol
Experimental: Cohort 3 - High-Dose; Placebo during 4-Week double-blind treatment period	Drug: Placebo (PB); Administered per the protocol; Drug: ALN-SOD; Administered per the protocol; Other: Diluent; Administered per the protocol
Experimental: Cohort 4 (Optional) - ≤ High Dose; Placebo during 4-Week double-blind treatment period	Drug: Placebo (PB); Administered per the protocol; Drug: ALN-SOD; Administered per the protocol; Other: Diluent; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-Emergent Adverse Event (TEAEs) in participants treated with ALN-SOD	At week 4 and through week 228
Severity of TEAEs in participants treated with ALN-SOD	At week 4 and through week 228

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentration of Neurofilament Light chain (NfL) in plasma over time	Up to approximately week 228
Change in concentration of NfL in plasma over time	Up to approximately week 228
Concentration of SOD1 protein in Cerebrospinal Fluid (CSF) over time	Up to approximately week 228
Change in concentration of SOD1 protein in CSF over time	Up to approximately week 228
Concentration of NfL in CSF over time	Up to approximately week 228
Change in concentration of NfL in CSF over time	Up to approximately week 228
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) over time	Up to approximately week 228
Concentration of ALN-SOD in plasma over time	Up to approximately week 228
Concentration of ALN-SOD in CSF over time	Up to approximately week 228
Incidence of Anti-Drug Antibodies (ADAs) to ALN-SOD in serum over time	Up to approximately week 228
Titer of ADAs to ALN-SOD in serum over time	Up to approximately week 228

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2024
• Primary Completion (Estimated): June 5, 2031
• Study Completion (Estimated): June 5, 2031

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Symptomatic; Known pathogenic mutation; Predicted pathogenic mutation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: ALN-SOD-ALS-2351; 2023-510344-20-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes