Clinical trial NCT06351592: First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Mutation in the Superoxide Dismutase-1 (SOD1) Gene
Keywords: Symptomatic
Known pathogenic mutation
Predicted pathogenic mutation
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-04-08
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse event (TEAEs) in participants treated with ALN-SOD
timeFrame: At week 4 and week 124
measure: Severity of TEAEs in participants treated with ALN-SOD
timeFrame: At week 4 and week 124
Secondary outcomes:
measure: Concentration of neurofilament light chain (NfL) in plasma over time
timeFrame: Up to approximately week 124
measure: Change in concentration of NfL in plasma over time
timeFrame: Up to approximately week 124
measure: Concentration of SOD1 protein in cerebrospinal fluid (CSF) over time
timeFrame: Up to approximately week 124
measure: Change in concentration of SOD1 protein in CSF over time
timeFrame: Up to approximately week 124
measure: Concentration of NfL in CSF over time
timeFrame: Up to approximately week 124
measure: Change in concentration of NfL in CSF over time
timeFrame: Up to approximately week 124
measure: Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) over time
timeFrame: Up to approximately week 124
measure: Concentration of ALN-SOD in plasma over time
timeFrame: Up to approximately week 124
measure: Concentration of ALN-SOD in CSF over time
timeFrame: Up to approximately week 124
measure: Incidence of anti-drug antibodies (ADAs) to ALN-SOD in serum over time
timeFrame: Up to approximately week 124
measure: Titer of ADAs to ALN-SOD in serum over time
timeFrame: Up to approximately week 124
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: University of Alberta Hospital, Edmonton
state: Alberta
city: London
country: Canada
facility: University Hospital - London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Tokushima-shi
country: Japan
facility: Tokushima University Hospital
state: Tokusima
city: Ota-ku
country: Japan
facility: Toho University Omori Medical Center
state: Tokyo
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: