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

Amyotrophic Lateral Sclerosis (ALS) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06351592
• Other study ID #: ALN-SOD-ALS-2351
• Secondary ID: 2023-510344-20-0
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 28, 2024
• Est. completion date: April 28, 2029

Study information

• Verified date: April 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is researching an experimental drug called ALN-SOD (called "study drug"). This study is focused on people with amyotrophic lateral sclerosis (ALS) who have a mutation 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 molecules 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 42
• Est. completion date: April 28, 2029
• Est. primary completion date: April 28, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, 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

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 the screening visit NOTE: Other protocol defined inclusion / exclusion criteria apply

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Amyotrophic Lateral Sclerosis (ALS)
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• ALN-SOD
Administered by intrathecal (IT) injection

Other:
• Diluent
Administered by IT injection

Drug:
• Placebo (PB)
Administered by IT injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse event (TEAEs) in participants treated with ALN-SOD		At week 4 and week 124
Primary	Severity of TEAEs in participants treated with ALN-SOD		At week 4 and week 124
Secondary	Concentration of SOD1 protein in cerebrospinal fluid (CSF) over time		Up to approximately week 124
Secondary	Change in concentration of SOD1 protein in CSF over time		Up to approximately week 124
Secondary	Concentration of neurofilament light chain (NfL) in plasma over time		Up to approximately week 124
Secondary	Change in concentration of NfL in plasma over time		Up to approximately week 124
Secondary	Concentration of NfL in CSF over time		Up to approximately week 124
Secondary	Change in concentration of NfL in CSF over time		Up to approximately week 124
Secondary	Concentration of ALN-SOD in plasma over time		Up to approximately week 124
Secondary	Concentration of ALN-SOD in CSF over time		Up to approximately week 124
Secondary	Incidence of anti-drug antibodies (ADAs) to ALN-SOD in serum over time		Up to approximately week 124
Secondary	Titer of ADAs to ALN-SOD in serum over time		Up to approximately week 124