First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS)
- Conditions
- Mutation in the Superoxide Dismutase-1 (SOD1) GeneAmyotrophic Lateral Sclerosis (ALS)
- Interventions
- Registration Number
- NCT06351592
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 42
- 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
- Slow vital capacity (SVC) ≥50% predicted value based on age, gender and height, measured in upright position
- Body Mass Index (BMI) ≤35 kg/m2 at time of screening
- 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
- Platelet count >50,000/microliter
- Has normal blood pressure readings, as defined in the protocol
Key
- Concurrent participation in another interventional clinical trial
- Has had a tracheostomy
- Has dementia, as assessed by the investigator
- Has uncontrolled psychiatric disease, including psychosis, active or recent suicidal ideation, untreated major depression, in the past 30 days
- 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
- Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter
- 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
- Was hospitalized (ie, >24 hours) for any reason other than ALS within 30 days of screening
- Has received treatment with tofersen within 6 months prior to screening
NOTE: Other protocol defined inclusion / exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 2 - Mid Dose ALN-SOD Placebo during double-blind treatment period Cohort 4 (Optional) ≤ High Dose Placebo (PB) Placebo during double-blind treatment period Cohort 3 - High Dose Diluent Placebo during double-blind treatment period Cohort 1 - Low Dose Diluent Placebo during double-blind treatment period Cohort 1 - Low Dose Placebo (PB) Placebo during double-blind treatment period Cohort 2 - Mid Dose Diluent Placebo during double-blind treatment period Cohort 3 - High Dose ALN-SOD Placebo during double-blind treatment period Cohort 3 - High Dose Placebo (PB) Placebo during double-blind treatment period Cohort 4 (Optional) ≤ High Dose ALN-SOD Placebo during double-blind treatment period Cohort 4 (Optional) ≤ High Dose Diluent Placebo during double-blind treatment period Cohort 2 - Mid Dose Placebo (PB) Placebo during double-blind treatment period Cohort 1 - Low Dose ALN-SOD Placebo during double-blind treatment period
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse event (TEAEs) in participants treated with ALN-SOD At week 4 and week 124 Severity of TEAEs in participants treated with ALN-SOD At week 4 and week 124
- Secondary Outcome Measures
Name Time Method Concentration of neurofilament light chain (NfL) in plasma over time Up to approximately week 124 Change in concentration of NfL in plasma over time Up to approximately week 124 Concentration of SOD1 protein in cerebrospinal fluid (CSF) over time Up to approximately week 124 Change in concentration of SOD1 protein in CSF over time Up to approximately week 124 Concentration of NfL in CSF over time Up to approximately week 124 Change in concentration of NfL in CSF over time Up to approximately week 124 Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) over time Up to approximately week 124 Concentration of ALN-SOD in plasma over time Up to approximately week 124 Concentration of ALN-SOD in CSF over time Up to approximately week 124 Incidence of anti-drug antibodies (ADAs) to ALN-SOD in serum over time Up to approximately week 124 Titer of ADAs to ALN-SOD in serum over time Up to approximately week 124
Trial Locations
- Locations (10)
University Hospital - London Health Sciences Centre
🇨🇦London, Ontario, Canada
University of Alberta Hospital, Edmonton
🇨🇦Edmonton, Alberta, Canada
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
Montreal Neurological Institute and Hospital
🇨🇦Montreal, Quebec, Canada
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Tokushima University Hospital
🇯🇵Tokushima-shi, Tokushima, Japan
Toho University Omori Medical Center
🇯🇵Ota-ku, Tokyo, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Hanyang University Seoul Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of