Amyotrophic Lateral Sclerosis (ALS), Mutation in the Superoxide Dismutase-1 (SOD1) Gene
Conditions
Keywords
Symptomatic, Known pathogenic mutation, Predicted pathogenic mutation
Brief 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) 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
Interventions
DRUGALN-SOD
Administered per the protocol
OTHERDiluent
Administered per the protocol
DRUGPlacebo (PB)
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Phase 1b: Dose Escalation - Double-blind, randomized, and single crossover Phase 2: Cohort Expansion - Open-label
Intervention model description
Phase 1b: Dose Escalation Phase 2: Cohort Expansion
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 /
Design outcomes
Primary
| 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
| 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 |
Countries
Australia, Belgium, Canada, Japan, South Korea, Taiwan
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed