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

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 1

Conditions: Mutation in the Superoxide Dismutase-1 (SOD1) Gene; Amyotrophic Lateral Sclerosis (ALS)

Treatments: Other: Diluent; Drug: ALN-SOD; Drug: Placebo (PB)

Study type: Interventional

Funder types: Industry

Identifiers

NCT06351592

2023-510344-20-00 (Registry Identifier)

ALN-SOD-ALS-2351

Details and patient eligibility

About

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

Enrollment: 42 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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42 participants in 4 patient groups

Cohort 1 - Low Dose

Experimental group

Description:

Placebo during double-blind treatment period

Treatment:

Drug: Placebo (PB)

Other: Diluent

Drug: ALN-SOD

Cohort 2 - Mid Dose

Experimental group

Description:

Placebo during double-blind treatment period

Treatment:

Drug: Placebo (PB)

Other: Diluent

Drug: ALN-SOD

Cohort 3 - High Dose

Experimental group

Description:

Placebo during double-blind treatment period

Treatment:

Drug: Placebo (PB)

Other: Diluent

Drug: ALN-SOD

Cohort 4 (Optional) ≤ High Dose

Experimental group

Description:

Placebo during double-blind treatment period

Treatment:

Drug: Placebo (PB)

Other: Diluent

Drug: ALN-SOD