Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06351592




Registration number
NCT06351592
Ethics application status
Date submitted
2/04/2024
Date registered
8/04/2024
Date last updated
7/08/2025

Titles & IDs
Public title
First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS)
Scientific 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
Secondary ID [1] 0 0
2023-510344-20-00
Secondary ID [2] 0 0
ALN-SOD-ALS-2351
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis (ALS) 0 0
Mutation in the Superoxide Dismutase-1 (SOD1) Gene 0 0
Condition category
Condition code
Neurological 0 0 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ALN-SOD
Other interventions - Diluent
Treatment: Drugs - Placebo (PB)

Experimental: Cohort 1 - Low Dose - Placebo during double-blind treatment period

Experimental: Cohort 2 - Mid Dose - Placebo during double-blind treatment period

Experimental: Cohort 3 - High Dose - Placebo during double-blind treatment period

Experimental: Cohort 4 (Optional) = High Dose - Placebo during double-blind treatment period


Treatment: Drugs: ALN-SOD
Administered by intrathecal (IT) injection

Other interventions: Diluent
Administered by IT injection

Treatment: Drugs: Placebo (PB)
Administered by IT injection
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse event (TEAEs) in participants treated with ALN-SOD
Timepoint [1] 0 0
At week 4 and week 124
Primary outcome [2] 0 0
Severity of TEAEs in participants treated with ALN-SOD
Timepoint [2] 0 0
At week 4 and week 124
Secondary outcome [1] 0 0
Concentration of neurofilament light chain (NfL) in plasma over time
Timepoint [1] 0 0
Up to approximately week 124
Secondary outcome [2] 0 0
Change in concentration of NfL in plasma over time
Timepoint [2] 0 0
Up to approximately week 124
Secondary outcome [3] 0 0
Concentration of SOD1 protein in cerebrospinal fluid (CSF) over time
Timepoint [3] 0 0
Up to approximately week 124
Secondary outcome [4] 0 0
Change in concentration of SOD1 protein in CSF over time
Timepoint [4] 0 0
Up to approximately week 124
Secondary outcome [5] 0 0
Concentration of NfL in CSF over time
Timepoint [5] 0 0
Up to approximately week 124
Secondary outcome [6] 0 0
Change in concentration of NfL in CSF over time
Timepoint [6] 0 0
Up to approximately week 124
Secondary outcome [7] 0 0
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) over time
Timepoint [7] 0 0
Up to approximately week 124
Secondary outcome [8] 0 0
Concentration of ALN-SOD in plasma over time
Timepoint [8] 0 0
Up to approximately week 124
Secondary outcome [9] 0 0
Concentration of ALN-SOD in CSF over time
Timepoint [9] 0 0
Up to approximately week 124
Secondary outcome [10] 0 0
Incidence of anti-drug antibodies (ADAs) to ALN-SOD in serum over time
Timepoint [10] 0 0
Up to approximately week 124
Secondary outcome [11] 0 0
Titer of ADAs to ALN-SOD in serum over time
Timepoint [11] 0 0
Up to approximately week 124

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/04/2029
Actual
Sample size
Target
42
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4575 - Birtinya
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Japan
State/province [4] 0 0
Hokkaido
Country [5] 0 0
Japan
State/province [5] 0 0
Tokushima
Country [6] 0 0
Japan
State/province [6] 0 0
Tokyo
Country [7] 0 0
Japan
State/province [7] 0 0
Kyoto
Country [8] 0 0
South Korea
State/province [8] 0 0
Seoul
Country [9] 0 0
Taiwan
State/province [9] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
844-734-6643
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
When Regeneron has:

* received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
* made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
* the legal authority to share the data, and
* ensured the ability to protect participant privacy
Available to whom?
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06351592