Nusinersen for Spinal Muscular Atrophy

(ONWARD Trial)

Not currently recruiting at 60 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Biogen

Must be taking: Nusinersen

Must not be taking: Other SMA therapies

Disqualifiers: Other investigational therapies, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 19

Duration: 64 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety of nusinersen, a treatment for spinal muscular atrophy (SMA), a condition affecting muscle movement. Researchers aim to assess nusinersen's impact on heart health, growth, and mobility over time by analyzing test results and monitoring side effects. Participants must have completed a previous SMA study (study 232SM203) to join. They will receive nusinersen every four months for nearly six years. The treatment is administered through a lumbar puncture, which injects the drug into the fluid around the spinal cord. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for SMA.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on another investigational therapy or an approved therapy for SMA after the previous study.

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

Research has shown that nusinersen is generally safe for people with spinal muscular atrophy (SMA). In earlier studies, fever, cough, pneumonia, and upper respiratory infections were the most common side effects. These side effects are typical for many treatments and are not considered serious.

Importantly, researchers have found no major safety issues related to nusinersen. Additionally, nusinersen is approved in over 71 countries for treating SMA in infants, children, and adults, indicating a strong safety record.

In summary, past research has demonstrated that nusinersen has a good safety profile, with most side effects being mild and manageable. ^{1 2 3 4 5}

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

Nusinersen is unique because it targets the underlying genetic cause of Spinal Muscular Atrophy (SMA) by boosting the production of the SMN protein, which is crucial for muscle function. Unlike other treatments that may focus more on managing symptoms, nusinersen is delivered directly into the spinal fluid through an intrathecal injection, allowing it to reach the central nervous system more effectively. Researchers are excited about this treatment because it offers a tailored approach, potentially providing more substantial and sustained benefits compared to traditional therapies for SMA.

What is the effectiveness track record for nusinersen in treating spinal muscular atrophy?

Studies have shown that nusinersen effectively treats spinal muscular atrophy (SMA). Research involving patients treated for up to 10 years indicates that nusinersen improves and maintains movement abilities in individuals with various types of SMA. This treatment has already received approval for SMA, underscoring its proven benefits. A thorough review of studies also supports its long-term effectiveness in many teenagers and adults with SMA. Additionally, real-world evidence confirms its safety and effectiveness over time, making it a reliable option for managing SMA symptoms. Participants in this trial will receive different dosages of nusinersen, based on their prior maintenance dose, to further evaluate its effectiveness and safety. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for individuals with spinal muscular atrophy (SMA) who completed the Day 302 visit in a prior study (NCT04089566). They must not have received other investigational therapies or participated in another interventional clinical study, nor started any approved SMA therapy after that specific visit.

Inclusion Criteria

Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol

Exclusion Criteria

Treatment with another investigational therapy or enrollment in another interventional clinical study

You have been treated with approved medication for spinal muscular atrophy after a certain study visit.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nusinersen through lumbar puncture every 4 months

64 months

Up to 19 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 to 8 weeks

Open-label extension

Participants continue to receive nusinersen to evaluate long-term safety and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Nusinersen

Trial Overview The trial is testing the long-term safety and effectiveness of higher doses of Nusinersen given through spinal injection to those with SMA. Participants are from a previous Nusinersen study and will continue to receive this drug to assess ongoing benefits and risks.

How Is the Trial Designed?

Group I: BIIB058 50/28 mg (Prior Maintenance Dose 12 mg) Experimental Treatment 1 Intervention

Participants who received maintenance dose of 12 mg nusinersen in study 232SM203 (NCT04089566), will receive loading dose of 50 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 1921.

Group II: BIIB058 28 mg (Prior Maintenance Dose 28 mg) Experimental Treatment 1 Intervention

Participants who received maintenance dose of 28 milligrams (mg) nusinersen in study 232SM203 (NCT04089566), will receive maintenance dose of 28 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 1921.

Nusinersen is already approved in United States, European Union for the following indications:

Approved in United States as Spinraza for:

• Spinal muscular atrophy in pediatric and adult patients

Approved in European Union as Spinraza for:

• Spinal muscular atrophy

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Published Research Related to This Trial

Nusinersen (SPINRAZA™) is an innovative treatment for spinal muscular atrophy (SMA) that works by modifying the splicing of SMN2 mRNA to increase the production of the essential SMN protein, which is crucial for motor neuron health.

The drug has been approved for intrathecal use in both pediatric and adult patients in the USA, marking a significant milestone in the treatment of SMA, with regulatory assessments ongoing in the EU and other countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen: First Global Approval. Hoy, SM.[2018]

Nusinersen, an antisense oligonucleotide, significantly improved motor function in 72% to 88% of patients with spinal muscular atrophy (SMA) types II and III over a treatment period of up to 26 months, as measured by the Hammersmith Functional Motor Scale-Expanded (HFMSE).

The treatment was found to be safe, with no significant side effects reported, making it a viable option for SMA patients, including those with severe scoliosis or requiring respiratory support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen for spinal muscular atrophy types II and III: a retrospective single-center study in South Korea. Shin, HJ., Na, JH., Lee, H., et al.[2023]

In a phase 1 study involving 28 children aged 2 to 14 with spinal muscular atrophy, 73 lumbar punctures were performed with a complication rate of 32%, primarily involving headaches and back pain.

The study found that adverse events were more common in older children and those with type 3 spinal muscular atrophy, suggesting that the size of the needle used also influenced the frequency of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. Haché, M., Swoboda, KJ., Sethna, N., et al.[2018]

Nusinersen (Spinraza) is the first approved drug for spinal muscular atrophy (SMA) and has shown significant improvements in motor function across all types of SMA in clinical trials.

The treatment is generally safe and well-tolerated, with common side effects including respiratory infections and headaches, but its administration via intrathecal delivery and high cost present challenges in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen: A Treatment for Spinal Muscular Atrophy. Claborn, MK., Stevens, DL., Walker, CK., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40576875/

Systematic Review and Meta-analysis of Long-Term ... Our findings demonstrate the long-term effectiveness of nusinersen in many adolescents and adults from a diverse SMA population.

2. investors.biogen.com investors.biogen.com/news-releases/news-release-details/new-data-nusinersen-underscore-biogens-commitment-advancing

New Data for Nusinersen Underscore Biogen's ... SPINRAZA has shown sustained efficacy across ages and SMA types with a well-established safety profile based on data in patients treated up to 10 years.

3. ninds.nih.gov ninds.nih.gov/about-ninds/what-we-do/impact/ninds-contributions-approved-therapies/nusinersen-spinrazar-spinal-muscular-atrophy-sma

Nusinersen (Spinraza®) – Spinal Muscular Atrophy (SMA) Nusinersen, marketed in the US as Spinraza ® (Biogen) is the first therapy approved for the treatment of SMA.

4. spinrazahcp.com spinrazahcp.com/en_us/home/why-spinraza/real-world-evidence.html

Real World Evidence SPINRAZA® (nusinersen) Efficacy Long-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study. Lancet Reg ...

5. ir.ionis.com ir.ionis.com/news-releases/news-release-details/new-data-highlight-potential-benefit-spinrazar-nusinersen

New data highlight potential benefit of SPINRAZA ... Interim results from the RESPOND study showed improved motor function in most participants treated with SPINRAZA following treatment with Zolgensma.

6. spinrazahcp.com spinrazahcp.com/en_us/home/why-spinraza/safety.html

SPINRAZA® (nusinersen) Side Effects and Safety Profile | HCP In the sham-controlled studies for patients with infantile-onset and later-onset SMA, 71 of 123 (58%) SPINRAZA-treated patients had elevated urine protein, ...

7. investors.biogen.com investors.biogen.com/news-releases/news-release-details/new-higher-dose-nusinersen-efficacy-and-safety-data-presented

New Higher Dose Nusinersen Efficacy and Safety Data ... SPINRAZA is approved in more than 71 countries to treat infants, children and adults with spinal muscular atrophy (SMA). As a foundation of care ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8248061/

Safety and efficacy of nusinersen in spinal muscular atrophy The most common AEs included pyrexia, cough, pneumonia, and upper respiratory tract infections. Motor milestone responder rates were higher in those receiving ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01494701

Study Details | NCT01494701 | An Open-label Safety, ... An Open-label Safety, Tolerability, and Dose-range Finding Study of Nusinersen (ISIS 396443) in Participants With Spinal Muscular Atrophy (SMA) (SMNRx).

10. ir.ionis.com ir.ionis.com/news-releases/news-release-details/ionis-pharmaceuticals-reports-data-update-nusinersen-phase-2

Release Details The latest analysis also demonstrates that no nusinersen-related safety or tolerability concerns have been identified. Including the nusinersen data, Ionis and ...