ALN-SOD for ALS

Recruiting at 22 trial locations

Overseen By Clinical 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 Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called ALN-SOD for individuals with a specific type of amyotrophic lateral sclerosis (ALS) linked to a change in the SOD1 gene. The main goal is to determine the drug's safety and how the body processes it. Researchers will also examine the drug's effects on certain markers in the blood and spinal fluid and assess its impact on ALS symptoms. Individuals with SOD1-ALS who experience muscle weakness and have not undergone a tracheostomy might be suitable for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that ALN-SOD is likely to be safe for humans?

Research has shown that ALN-SOD is a new drug tested for people with a specific type of ALS related to the SOD1 gene. This marks the first use of ALN-SOD in humans, so direct safety information is not yet available. As this study is in its early stages, the primary goal is to assess the drug's safety and tolerability. Early-phase trials often have limited safety data, and researchers will closely monitor for any side effects. Participants might encounter unknown risks, which is common when drugs are first tested in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ALS?

Researchers are excited about ALN-SOD for ALS because it targets the root cause of the disease in a new way. Unlike current treatments that mainly focus on managing symptoms, ALN-SOD is designed to specifically silence the SOD1 gene, which is known to contribute to ALS in certain patients. This gene-silencing approach could potentially slow down or even halt disease progression, offering hope for more effective long-term management of ALS. Additionally, ALN-SOD's innovative mechanism sets it apart from existing therapies, which often have limited impact on the underlying disease process.

What evidence suggests that ALN-SOD might be an effective treatment for SOD1-ALS?

Research has shown that focusing on the SOD1 gene can help manage ALS symptoms. Tofersen, a drug targeting SOD1, has shown promise in slowing the disease in patients with SOD1-ALS. Studies found that it effectively lowers SOD1 levels and improves patient outcomes over time. Although ALN-SOD, the investigational treatment in this trial, is new and untested in people, it works similarly by aiming to reduce harmful SOD1 protein levels. This approach appears promising based on the success of similar treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Cohort 4 (Optional) ≤ High Dose Experimental Treatment 3 Interventions

Placebo during double-blind treatment period

Group II: Cohort 3 - High Dose Experimental Treatment 3 Interventions

Placebo during double-blind treatment period

Group III: Cohort 2 - Mid Dose Experimental Treatment 3 Interventions

Placebo during double-blind treatment period

Group IV: Cohort 1 - Low Dose Experimental Treatment 3 Interventions

Placebo during double-blind treatment period

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

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 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]

Antisense oligonucleotide therapy targeting SOD1 significantly reduced SOD1 messenger RNA and protein levels in the brains and cerebrospinal fluid (CSF) of SOD1G93A rats, indicating its potential efficacy in lowering SOD1 levels in ALS.

SOD1 levels in human CSF were found to be higher in ALS patients compared to healthy controls, suggesting that CSF SOD1 could serve as a stable pharmacodynamic marker for monitoring the effectiveness of SOD1-lowering therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SOD1 in cerebral spinal fluid as a pharmacodynamic marker for antisense oligonucleotide therapy. Winer, L., Srinivasan, D., Chun, S., 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]

In a study of 23 patients with sporadic ALS (SALS), sequencing the entire SOD1 gene revealed novel genetic variants in 30% of the patients' brain samples, indicating a potential role of SOD1 in SALS.

Two novel variants, one in the SOD1 promoter and another in intron 1, may have functional implications for the disease, suggesting that while no clear mutations were identified, these variants could influence the development of SALS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An analysis of the entire SOD1 gene in sporadic ALS. Luquin, N., Yu, B., Trent, RJ., et al.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06351592

NCT06351592 | First in Human (FIH) Study of ALN-SOD ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12003547/

Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic ... Current evidence suggests that tofersen effectively reduces SOD1 and NfL levels and slow disease progression in SOD1 ALS, showing promise as a targeted ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2204705

Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS At 52 weeks, the change in the ALSFRS-R score was −6.0 in the early-start cohort and −9.5 in the delayed-start cohort (difference, 3.5 points; ...

4. translationalneurodegeneration.biomedcentral.com translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-024-00416-x

Variability in SOD1-associated amyotrophic lateral sclerosis Their study reported a 38.8% reduction in cytosolic SOD (mainly SOD1) activity in post-mortem brain tissues of ALS patients with SOD1 mutations ...

5. als-mnd.org als-mnd.org/support-for-pals-cals/drugs-in-development/sod1-therapies-trials/

SOD1 Therapies & Trials Early intervention has long been considered as likely optimal in ALS/MND, though it has never been clinically tested.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02623699

Study Details | NCT02623699 | An Efficacy, Safety, ... The primary objective of Part C of this study is to evaluate the clinical efficacy of tofersen administered to adults with ALS and a confirmed SOD1 mutation.

7. clinicaltrials.eu clinicaltrials.eu/inn/aln-1395762/

Aln-1395762 – Application in Therapy and Current Clinical ... ALN-1395762, also known as ALN-SOD, is a small interfering RNA (siRNA) drug being tested for the treatment of ALS associated with SOD1 gene mutations. In this ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11138100/

Variability in SOD1-associated amyotrophic lateral sclerosis Their study reported a 38.8% reduction in cytosolic SOD (mainly SOD1) activity in post-mortem brain tissues of ALS patients with SOD1 mutations ...

9. link.springer.com link.springer.com/article/10.1007/s10072-025-07994-2

Tofersen for SOD1 amyotrophic lateral sclerosis This systematic review and meta-analysis aimed to summarize the current evidence on efficacy and safety of tofersen for SOD1 ALS. In terms of ...