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Compensation: Varies

Number of Visits: 19

Duration: 64 months

115 Participants Needed

Nusinersen for Spinal Muscular Atrophy
(ONWARD Trial)

Recruiting at 52 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 GroupAll 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 DataThis treatment has passed at least one previous human trial

Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

In this study, researchers will learn more about the use of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study is an extension study and will enroll only those participants who have completed treatment in the parent study, 232SM203. The main goal of the study is to learn about the long-term safety of nusinersen. The main questions researchers want to answer are: * How many participants have adverse events and serious adverse events during the study? * How do the results of electrocardiograms (ECGs), vital signs, and laboratory tests including blood and urine tests change after treatment? * How many participants have a low platelet count after treatment? * How many participants had a change in the time it took for their heart to recharge between beats after treatment? * How does each participant's height and other measures of growth change after treatment? * How much do the results of neurological exams that check movement, reflexes, and brain function change after treatment? Researchers will also learn about the effect of nusinersen on mobility using various tests. They will study body movements, reflexes, balance, and coordination. They will also record if participants need help with breathing. The 232SM302 study will be done as follows: * Participants will be screened to check if they can join the study. * Participants will receive their 1st dose of nusinersen in this study about 4 months after their final dose in the parent study. * Each participant will receive nusinersen once every 4 months during the treatment period. * Nusinersen will be given through a lumbar puncture, which involves injecting the drug into the fluid around the spinal cord in the lower back. * The treatment period will last for up to 64 months (1921 days). * There will be a follow-up safety period that lasts from 4 to 8 weeks. * In total, participants will have up to 19 study visits. Participants will stay in the study for close to 6 years.

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.

What data supports the effectiveness of the drug Nusinersen for treating spinal muscular atrophy?

Research shows that Nusinersen, a drug that helps increase the production of a crucial protein for nerve cells, is effective in treating spinal muscular atrophy (SMA) by improving muscle strength and function in both children and adults with SMA.¹ ² ³ ⁴ ⁵

Is Nusinersen safe for humans?

Nusinersen, also known as Spinraza, has been studied for safety in children with spinal muscular atrophy. In clinical trials, some children experienced side effects like headaches and back pain after receiving the treatment, but these were similar to what is typically seen with the procedure used to administer the drug.¹ ² ³ ⁴ ⁶

How is the drug Nusinersen unique in treating spinal muscular atrophy?

Nusinersen is unique because it is an antisense oligonucleotide drug that is administered directly into the spinal fluid (intrathecally) to increase the production of a crucial protein called SMN, which is often lacking in patients with spinal muscular atrophy. This approach specifically targets the genetic cause of the disease, making it different from other treatments that may not address the underlying genetic issue.¹ ² ³ ⁴ ⁷

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

2Treatment groups

Experimental Treatment

Group I: BIIB058 50/28 mg (Prior Maintenance Dose 12 mg)Experimental Treatment1 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 Treatment1 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

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

Findings from Research

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]

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]

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]