Nusinersen for SMA

(RESPOND Trial)

No longer recruiting at 29 trial locations
UB
GB
Overseen ByGlobal Biogen Clinical Trial Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how nusinersen affects muscle and movement abilities in young children with spinal muscular atrophy (SMA) who continue to struggle after previous gene therapy. Researchers aim to observe improvements in motor functions, such as sitting and crawling, while monitoring safety and any side effects. This study suits children under 3 years old with SMA who have had limited success with the gene therapy onasemnogene abeparvovec. Participants will receive nusinersen through a lumbar puncture (an injection into the lower back) over several months. Researchers will closely monitor safety and movement abilities throughout the study. As a Phase 4 trial, this research helps determine how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have been treated with certain investigational drugs or treatments for SMA other than onasemnogene abeparvovec within 30 days before the study.

What is the safety track record for nusinersen?

Research has shown that nusinersen is generally safe for people with spinal muscular atrophy (SMA). In earlier studies, about 58% of those treated experienced higher protein levels in their urine, but no major safety issues were directly linked to nusinersen.

Reported side effects include fever, cough, pneumonia, and upper respiratory infections. Despite these, the treatment is widely used and approved in over 71 countries for people of all ages with SMA, indicating its safety.

Overall, while some side effects exist, past research has not identified serious safety problems with nusinersen.12345

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Nusinersen for treating spinal muscular atrophy (SMA) because it offers a targeted approach by boosting the production of the survival motor neuron (SMN) protein, which is crucial for muscle function. Unlike other treatments that might focus on managing symptoms or providing general support, Nusinersen is administered directly into the spinal fluid via intrathecal injection, allowing it to act directly on the central nervous system where it's needed most. This targeted delivery method is designed to help improve or stabilize motor function in patients with SMA, offering a potentially significant improvement over conventional therapies.

What is the effectiveness track record for nusinersen in treating SMA?

Studies have shown that nusinersen can improve movement in people with spinal muscular atrophy (SMA). Research indicates that patients treated with nusinersen, also known as SPINRAZA, have experienced lasting improvements in movement, regardless of age or type of SMA. Specifically, early results from the RESPOND study showed that many participants who had already received the gene therapy Zolgensma saw further improvement in motor skills when treated with nusinersen. With a well-established safety record and evidence supporting its effectiveness over many years, nusinersen offers hope for enhancing muscle and movement abilities in children with SMA.678910

Who Is on the Research Team?

MD

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for children under 36 months with Spinal Muscular Atrophy who have a specific genetic mutation and at least one copy of the SMN2 gene. They must have previously received onasemnogene abeparvovec, not been exposed to Nusinersen before, and can't be suffering from severe side effects related to onasemnogene abeparvovec.

Inclusion Criteria

Your overall health condition is not good enough according to the doctor in charge.
I received IV onasemnogene abeparvovec after showing symptoms of SMA.
My genetic test shows I have at least one copy of the SMN2 gene.
See 13 more

Exclusion Criteria

I am experiencing severe side effects from onasemnogene abeparvovec treatment.
I haven't used any experimental drugs or treatments for SMA, except onasemnogene abeparvovec.
My child's weight is below the third percentile for their age, according to WHO standards.
See 1 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Treatment

Participants receive 4 initial doses of 12 mg of nusinersen on Days 1, 15, 29, and 64, followed by maintenance doses every 4 months

95 weeks
14 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks
2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • Nusinersen
Trial Overview The study tests the effectiveness of Nusinersen in young patients with SMA who've already been treated with onasemnogene abeparvovec. It aims to see if additional treatment improves clinical outcomes and assesses safety and tolerability.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Nusinersen 12 mgExperimental Treatment1 Intervention

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

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Approved in United States as Spinraza for:
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Approved in European Union as Spinraza for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials
655
Recruited
468,000+
Daniel Quirk profile image

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher profile image

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

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

Published Research Related to This Trial

A study analyzing 3,940 cases from the FDA Adverse Event Reporting System found that taxane-related neurotoxicity, particularly peripheral neuropathy, is common, especially among elderly patients and females.
The median time for neurological adverse effects to appear after taxane treatment was 27 days, with a significant portion of cases occurring within the first 30 days, and the study reported a fatality rate of 6.13% and hospitalization rate of 28.63% for these adverse events.
Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017-2021.Zhang, J., Luo, L., Long, E., et al.[2023]
A pooled analysis of the ABOUND clinical trial program showed that nab-paclitaxel-based regimens provide median progression-free survival (PFS) of 4.1 months for patients with poor performance status (ECOG PS 2) and up to 7.7 months for patients with diabetes, indicating varying efficacy based on patient comorbidities.
Overall survival (OS) rates were 18.2 months for patients with renal impairment and 16.1 months for elderly patients, but those with ECOG PS 2 had significantly shorter OS at 5.6 months, highlighting the need for careful treatment consideration in vulnerable populations.
nab-Paclitaxel/Carboplatin in Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis.Langer, CJ., Gajra, A., Gridelli, C., et al.[2022]

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/38361750/
Long-term efficacy and safety of nusinersen in adults with ...We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from ...
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.
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.
Real World Evidence SPINRAZA® (nusinersen) Efficacy | HCPLong-term efficacy and safety of nusinersen in adults with 5q spinal muscular atrophy: a prospective European multinational observational study. Lancet Reg ...
NCT02292537 | A Study to Assess the Efficacy and Safety ...The primary objective of this study is to examine the clinical efficacy of nusinersen (ISIS 396443) administered intrathecally to participants with later-onset ...
SPINRAZA® (nusinersen) Side Effects and Safety Profile | HCPIn the sham-controlled studies for patients with infantile-onset and later-onset SMA, 71 of 123 (58%) SPINRAZA-treated patients had elevated urine protein, ...
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 ...
Safety and efficacy of nusinersen in spinal muscular atrophyThe most common AEs included pyrexia, cough, pneumonia, and upper respiratory tract infections. Motor milestone responder rates were higher in those receiving ...
Release DetailsThe latest analysis also demonstrates that no nusinersen-related safety or tolerability concerns have been identified. Including the nusinersen data, Ionis and ...
SPINRAZA (nusinersen) injection, for intrathecal useThe safety of SPINRAZA was studied in infants with symptomatic SMA, approximately 1 month to. 8 months of age at study entry; in a sham-controlled trial (n=80 ...
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