Apply to Trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

42 Participants Needed

ALN-SOD for ALS

Recruiting at 15 trial locations

Overseen ByClinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Tofersen

Disqualifiers: Dementia, Uncontrolled psychiatric disease, others

No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial requires that if you are taking riluzole or edaravone, you must be on a stable dose for at least 4 weeks before starting the study and continue at that dose throughout the study. The protocol does not specify about other medications.

How does the drug ALN-SOD differ from other ALS treatments?

ALN-SOD is unique because it targets the SOD1 gene, which is linked to both familial and sporadic ALS, potentially addressing a common molecular event in the disease's pathogenesis. This approach is different from other treatments that may not specifically target this gene or its associated pathways.¹ ² ³ ⁴ ⁵

What is the purpose of this trial?

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

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

This trial is for adults with ALS caused by a SOD1 gene mutation. Participants should have an SVC of at least 50% the predicted value, a BMI of 35 or less, and stable doses if taking specific ALS medications. They must not have low platelet counts or abnormal blood pressure.

Inclusion Criteria

My blood pressure is within the normal range.

Body Mass Index (BMI) ≤35 kg/m2 at time of screening

Platelet count >50,000/microliter

See 3 more

Exclusion Criteria

Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter

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

Concurrent participation in another interventional clinical trial

See 5 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multiple ascending doses of ALN-SOD to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

ALN-SOD

Trial Overview The study tests ALN-SOD, an experimental drug for 'SOD1-ALS'. It's the first time this drug is used in humans to evaluate safety and effects on ALS symptoms, biomarkers in blood/CSF, drug levels over time, and potential antibody development against it.

Participant Groups

4Treatment groups

Experimental Treatment

Group I: Cohort 4 (Optional) ≤ High DoseExperimental Treatment3 Interventions

Placebo during double-blind treatment period

Group II: Cohort 3 - High DoseExperimental Treatment3 Interventions

Placebo during double-blind treatment period

Group III: Cohort 2 - Mid DoseExperimental Treatment3 Interventions

Placebo during double-blind treatment period

Group IV: Cohort 1 - Low DoseExperimental Treatment3 Interventions

Placebo during double-blind treatment period

Find a Clinic Near You

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Findings from Research

A novel biomarker associated with both sporadic (SALS) and familial (FALS) amyotrophic lateral sclerosis (ALS) was identified, revealing a common molecular event linked to the SOD1 gene, which is crucial for understanding ALS pathogenesis.

Using covalent chemical modification techniques, researchers discovered a specific 32-kDa SOD1-containing protein that is present in both SALS and FALS, but not in other neurodegenerative diseases, suggesting a unique pathway in ALS development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis.Gruzman, A., Wood, WL., Alpert, E., et al.[2022]

The small molecule SRI-22818 has been shown to increase NF-κB expression and SOD2 levels, which may help combat the degeneration of motor neurons in ALS, a disease linked to SOD1 mutations.

SRI-22818 has demonstrated activity in vivo in a mouse model of ALS (SOD1-G93A), suggesting its potential as a therapeutic intervention for this progressive neurodegenerative disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of novel small molecules for the treatment of ALS.Mathew, B., Ruiz, P., Pathak, V., et al.[2021]

The study identified that the D90A and E100K mutations in the SOD1 gene, previously thought to be linked to ALS, do not consistently segregate with the disease in affected families, suggesting they are not the sole cause of ALS in these cases.

This research indicates that some SOD1 mutations may follow a more complex inheritance pattern, which could impact genetic testing and counseling for ALS, as it challenges the notion that these mutations are definitive indicators of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four familial ALS pedigrees discordant for two SOD1 mutations: are all SOD1 mutations pathogenic?Felbecker, A., Camu, W., Valdmanis, PN., et al.[2017]