ION363 for ALS

Not currently recruiting at 33 trial locations

Overseen By Ionis Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Ionis Pharmaceuticals, Inc.

Must be taking: Edaravone, Riluzole, Relyvrio, others

Must not be taking: Antiplatelets, Anticoagulants, others

Disqualifiers: Ventilation, HIV, Hepatitis, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 36

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ION363 for individuals with a specific type of ALS (amyotrophic lateral sclerosis) linked to a genetic mutation called FUS. The researchers aim to determine if ION363 can improve patient function and extend life expectancy. Participants will receive either ION363 or a placebo (a substance with no active drug) to compare results. This trial may suit those with ALS symptoms and a confirmed FUS genetic mutation. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that participants taking edaravone, riluzole, Relyvrio, sodium phenylbutyrate, or tauroursodeoxycholic acid must be on a stable dose for at least 28 days before starting the study and continue on that dose during the study, unless a doctor advises otherwise. For other medications, they should be stable for at least 1 month before the study, but changes may be allowed with approval.

Is there any evidence suggesting that ION363 is likely to be safe for humans?

Research shows that ION363 has been tested in various settings, including the FDA's expanded access program. In these trials, several patients with ALS (amyotrophic lateral sclerosis) received this treatment. So far, results suggest that ION363 is generally well-tolerated.

For one patient with a specific ALS mutation, researchers administered repeated doses of ION363 through an injection into the spinal area. This method appeared to reduce levels of the harmful protein linked to the disease. While the treatment remains under study, these results are promising for safety.

ION363 is currently being tested in a later phase of clinical trials, which typically involves more participants and examines both safety and effectiveness. This indicates that earlier studies have already provided some evidence of safety. However, like any treatment, there might be risks, and ongoing research is essential to fully understand them. ^{1 2 3 4 5}

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

Unlike the standard treatments for ALS, which often focus on managing symptoms with medications like Riluzole and Edaravone, ION363 offers a novel approach by targeting the disease at a genetic level. Researchers are excited about ION363 because it is administered directly into the spinal fluid via lumbar intrathecal injection, potentially allowing for more direct and effective delivery to the central nervous system. This targeted approach could slow down the progression of ALS more effectively than current treatments, offering hope for improved outcomes in patients.

What evidence suggests that ION363 might be an effective treatment for ALS?

Research has shown that ION363, also known as jacifusen, might help treat ALS in people with specific changes in the FUS gene. Studies have found that ION363 can delay nerve cell damage in animals, suggesting it might slow the disease's progression in humans. ION363 reduces the production of harmful proteins from the FUS gene. Early results indicate that it is safe and could improve survival and function for those with this type of ALS. This trial will compare ION363 with a placebo to evaluate its effectiveness and safety, offering hope that ION363 could be an effective treatment option for patients with FUS-ALS. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for ALS patients with FUS mutations. Adults over 30 and children aged 12-65 can join if they meet certain disease progression rates and breathing capacity criteria. Participants must have stable medication use, a caregiver to report on their condition, and no recent participation in other trials or treatments like gene therapy.

Inclusion Criteria

I am 12-65 years old with ALS symptoms, and if I'm 30-65, my ALS is progressing quickly.

I am over 30, show ALS symptoms, and my ALS condition is progressing slowly.

I have been on a stable dose of edaravone and/or riluzole for at least 28 days and can continue it during the study.

Exclusion Criteria

I have never had gene therapy, cell transplantation, or experimental brain surgery.

I haven't taken any experimental drugs or used new medical devices recently.

My blood pressure is not higher than 160/100 mm Hg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Part 1)

Participants receive a multi-dose regimen of ION363 or placebo for 60 weeks

60 weeks

Every 12 weeks, with an additional loading dose at 4 weeks

Open-label Extension (Part 2)

Participants receive open-label ION363 for 84 weeks

84 weeks

Every 12 weeks, with an additional loading dose at 4 weeks

Long-term Extension (Part 3)

Participants may continue to receive open-label ION363 for up to 3 additional years or until ION363 becomes commercially available

Up to 3 years

Every 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ION363

Trial Overview The study tests ION363's effect on ALS symptoms and survival compared to a placebo. It aims to understand how the drug works in the body (pharmacokinetics) and its impact on the disease process (pharmacodynamics).

How Is the Trial Designed?

Group I: ION363 Experimental Treatment 1 Intervention

ION363 will be administered by lumbar intrathecal (IT) bolus injection every 12 weeks, with an additional loading dose at 4 weeks, over a 60-week double-blind treatment period in Part 1; every 12 weeks for 84 weeks in the open-label extension treatment period (Part 2), with an additional loading dose administered 4 weeks after the first dose. Patients may continue to receive open-label ION363 every 12 weeks in Part 3 for up to 3 additional years or until ION363 becomes commercially available in the patient's country or until the Sponsor discontinues the development program, whichever occurs earlier.

Group II: Placebo Placebo Group 1 Intervention

Placebo will be administered by lumbar IT bolus injection every12 weeks, with an additional loading dose at 4 weeks, over a 60-week double-blind treatment period (Part 1).

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04768972

NCT04768972 | FUSION: A Study to Evaluate the Efficacy, ... The primary purpose of this study is to evaluate the efficacy of ION363 on clinical function and survival in carriers of fused in sarcoma mutations with ...

2. oligotherapeutics.org oligotherapeutics.org/targeting-als-fus-early-insights-from-the-jacifusen-ion363-case-series/

Targeting ALS-FUS: Early Insights from the Jacifusen ... The findings provide sufficient data to demonstrate that the drug is safe and may have potential efficacy for treating FUS-ALS, enabling a Phase ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625005136

Antisense oligonucleotide jacifusen for FUS-ALS Jacifusen is an antisense oligonucleotide targeting FUS pre-mRNA, previously shown to delay neurodegeneration in a mouse model and potentially slow functional ...

4. als-mnd.org als-mnd.org/support-for-pals-cals/drugs-in-development/ulefnersen/

Ulefnersen – Ionis Pharmaceuticals Ulefnersen is an ASO designed to target the Fused in Sarcoma (FUS) gene, which is found to be mutated in 0.3-0.9% of ALS/MND cases, often manifesting early ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8799464/

Antisense oligonucleotide silencing of FUS expression as a ... We provide evidence to support the clinical application of ION363 in the treatment of ALS-FUS and related FUS-dependent proteinopathies. Results. Selective MN ...

6. neals.org neals.org/als-trials/nct04768972

A Phase 1-3 Study to Evaluate the Efficacy, Safety, ... The primary purpose of this study is to evaluate the clinical efficacy of ION363 on clinical function and survival in carriers of fused in sarcoma mutations ...