High-Dose Nusinersen for Spinal Muscular Atrophy (ASCEND Trial)
Palo Alto (17 mi)Age: < 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Biogen
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?The primary objective of this study is to evaluate motor function following treatment with HD nusinersen in participants with spinal muscular atrophy (SMA) previously treated with risdiplam.
The secondary objective of this study is to evaluate the safety and tolerability of HD nusinersen in participants with SMA previously treated with risdiplam.
Is the drug Nusinersen a promising treatment for Spinal Muscular Atrophy?Yes, Nusinersen is a promising drug for treating Spinal Muscular Atrophy. It helps increase the production of a crucial protein needed for muscle strength and has been approved for use in both children and adults.12346
What safety data is available for high-dose Nusinersen in treating spinal muscular atrophy?Safety data for Nusinersen, also known as Spinraza, includes findings from various studies and post-marketing surveillance. In a phase 1 study involving 28 children with SMA types 2 and 3, 73 lumbar punctures were performed, with 32% resulting in adverse events such as headaches, back pain, and post-lumbar puncture syndrome. A post-marketing surveillance in Japan involving 401 patients reported a 31.7% incidence of adverse events, with headaches, pyrexia, and pneumonia being the most common. Serious adverse events occurred in 11.5% of cases. Overall, the safety profile of Nusinersen is consistent with known data, and no new safety concerns have been identified.13567
What data supports the idea that High-Dose Nusinersen for Spinal Muscular Atrophy is an effective drug?The available research shows that Nusinersen is effective in treating spinal muscular atrophy (SMA). Studies have demonstrated its safety and effectiveness in both children and adults with SMA types II and III. For example, a study in South Korea found that Nusinersen was effective even in patients with severe conditions like scoliosis or those needing respiratory support. Additionally, a large study in Japan involving 524 patients confirmed its effectiveness in real-world settings. These findings suggest that Nusinersen is a beneficial treatment for SMA, providing improvements in patients' conditions.13468
Do I have to stop taking my current medications for this trial?Yes, you will need to stop taking risdiplam before starting the trial. The protocol does not specify about other medications, so it's best to discuss with the trial team.
Eligibility Criteria
This trial is for individuals aged 15-50 with a confirmed genetic diagnosis of spinal muscular atrophy (SMA), weighing over 20 kg, and able to perform certain functional assessments. Participants must have been previously treated with risdiplam but are willing to stop it and start high-dose nusinersen treatment. They should not be able to walk independently for 15 feet, not have severe illnesses or conditions that could affect the study, nor be pregnant or breastfeeding.Inclusion Criteria
My upper limb mobility score is 3 or higher.
My RULM score is between 5 and 30.
I am willing to stop taking risdiplam.
I have been taking risdiplam as prescribed or through a special program.
I have been treated with risdiplam for at least 6 months and have not used nusinersen.
My SMA symptoms started after I was 6 months old.
I weigh more than 20 kilograms.
I have a confirmed genetic form of SMA due to SMN1 gene changes.
I stopped taking nusinersen over 16 months ago and have been on risdiplam for more than 12 months.
I cannot walk 15 feet on my own without help.
I am between 15 and 50 years old.
I am ready and can start treatment with HD nusinersen.
Exclusion Criteria
I haven't had a major illness in the month before my screening or in the week leading up to my first dose.
I have had bacterial meningitis, viral encephalitis, or hydrocephalus.
I am not pregnant, breastfeeding, nor planning to become pregnant during the study.
I have an active infection that needs treatment with antibiotics or antivirals.
Treatment Details
The trial is testing whether a higher dose of nusinersen can improve motor function in patients who have SMA and were previously treated with risdiplam. It will also assess the safety and tolerability of this increased dosage regimen.
1Treatment groups
Experimental Treatment
Group I: Higher Dose NusinersenExperimental Treatment1 Intervention
All participants in the core study period, previously treated with risdiplam (nusinersen-naive participants and nusinersen-experienced participants), will receive HD nusinersen, administered as 2 loading doses of 50 milligrams (mg) each, approximately 2 weeks apart, followed by maintenance doses of 28 mg approximately every 4 months. Following the core study period, participants may be given the opportunity to receive maintenance doses of 28 mg nusinersen administered approximately every 4 months up to 2 years during the optional long-term extension (LTE) period.
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
Research locations nearbySelect from list below to view details:
Rare Disease Research InstituteAtlanta, GA
Arkansas Children'sLittle Rock, AR
Research SitePhiladelphia, PA
Atrium Health Wake Forest BaptistWinston-Salem, NC
More Trial Locations
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Who is running the clinical trial?
BiogenLead Sponsor
References
Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. [2018]Nusinersen (ISIS-SMNRx or ISIS 396443) is an antisense oligonucleotide drug administered intrathecally to treat spinal muscular atrophy. We summarize lumbar puncture experience in children with spinal muscular atrophy during a phase 1 open-label study of nusinersen and its extension. During the studies, 73 lumbar punctures were performed in 28 patients 2 to 14 years of age with type 2/3 spinal muscular atrophy. No complications occurred in 50 (68%) lumbar punctures; in 23 (32%) procedures, adverse events were attributed to lumbar puncture. Most common adverse events were headache (n = 9), back pain (n = 9), and post-lumbar puncture syndrome (n = 8). In a subgroup analysis, adverse events were more frequent in older children, children with type 3 spinal muscular atrophy, and with a 21- or 22-gauge needle compared to a 24-gauge needle or smaller. Lumbar punctures were successfully performed in children with spinal muscular atrophy; lumbar puncture-related adverse event frequency was similar to that previously reported in children.
Nusinersen: First Global Approval. [2018]Spinal muscular atrophy (SMA) is a rare autosomal recessive disorder characterized by muscle atrophy and weakness resulting from motor neuron degeneration in the spinal cord and brainstem. It is most commonly caused by insufficient levels of survival motor neuron (SMN) protein (which is critical for motor neuron maintenance) secondary to deletions or mutations in the SMN1 gene. Nusinersen (SPINRAZA™) is a modified antisense oligonucleotide that binds to a specific sequence in the intron, downstream of exon 7 on the pre-messenger ribonucleic acid (pre-mRNA) of the SMN2 gene. This modulates the splicing of the SMN2 mRNA transcript to include exon 7, thereby increasing the production of full-length SMN protein. Nusinersen is approved in the USA for intrathecal use in paediatric and adult patients with SMA. Regulatory assessments for nusinersen as a treatment for SMA are underway in the EU and several other countries. This article summarizes the milestones in the development of nusinersen leading to this first approval for SMA in paediatric and adult patients.
Nusinersen: A Treatment for Spinal Muscular Atrophy. [2020]To review the efficacy and safety of nusinersen (Spinraza) in the treatment of spinal muscular atrophy (SMA).
Nusinersen injections in adults and children with spinal muscular atrophy: a single-center experience. [2021]Nusinersen is a drug approved in December 2016 for treatment of spinal muscular atrophy (SMA). We want to share our initial experience with image-guided, non-image-guided, and port-delivered nusinersen injections in a large single-center SMA patient cohort, treating both pediatric and adult patients with focus on technical considerations and other patient concerns from a combined perspective of patient, neurologist, and radiologist.
Real-world safety and effectiveness of nusinersen, a treatment for spinal muscular atrophy, in 401 Japanese patients: results from an interim analysis of post-marketing surveillance. [2022]Purpose: Nusinersen is an antisense oligonucleotide for the treatment of spinal muscular atrophy (SMA). A post-marketing surveillance (PMS) has been ongoing (August 2017-August 2025) in all patients in Japan who received intrathecal nusinersen in real-world clinical settings. We report the interim analysis results of safety and effectiveness.Methods: This interim analysis was conducted using data collected from 401 patients whose case report forms were obtained at least once by 30 May 2020. Collected data included patient demographics and adverse events (AEs) for safety, and motor function assessments and Clinical Global Impressions of Improvement (CGI-I) for effectiveness.Results: All 401 patients were diagnosed with SMA and were included in the safety and effectiveness analysis (infantile-onset SMA [n = 126, 31.4%], later-onset SMA [n = 275, 68.6%]). The median duration of treatment was 330 days (range 1-823 days). The incidence proportion of AEs was 31.7% (37.3% in infantile-onset SMA and 29.1% in later-onset SMA). The most common AEs were headache (4.5%), pyrexia (4.2%), and pneumonia (3.7%). The incidence proportion of serious AEs was 11.5%. Nusinersen improved motor function scores and was assessed as 'effective' based on CGI-I in 99.7-100% of patients.Conclusions: This interim analysis of the PMS in Japanese patients treated with nusinersen found no new safety concerns, with the type of AEs consistent with the expected safety profile. The benefit-risk balance of nusinersen treatment remains favorable.
Nusinersen for spinal muscular atrophy types II and III: a retrospective single-center study in South Korea. [2023]This study investigated the efficacy and safety of nusinersen, an antisense oligonucleotide, in patients with spinal muscular atrophy (SMA) types II (OMIM: 253,550) or III (OMIM: 253,400), including those with severe scoliosis or requiring respiratory support via mechanical ventilation.
Adverse events in the treatment of spinal muscular atrophy in children and adolescents with nusinersen: A systematic review and meta-analysis. [2023]To systematically analyze adverse events (AEs) in treatment of spinal muscular atrophy (SMA) with Nusinersen in children and adolescents.
Safety and effectiveness of nusinersen, a treatment for spinal muscular atrophy, in 524 patients: results from an interim analysis of post-marketing surveillance in Japan. [2023]Nusinersen is an antisense oligonucleotide approved for the treatment of spinal muscular atrophy (SMA). A post-marketing surveillance (PMS) has been ongoing (August 2017-August 2025) in all patients in Japan who were administered nusinersen intrathecally in real-world clinical settings. We report the interim analysis results for safety and effectiveness.