Nusinersen for Spinal Muscular Atrophy

(PIERRE-PK Trial)

Recruiting at 17 trial locations

Overseen By Global Biogen Clinical Trial Center

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Biogen

Must be taking: Nusinersen

Disqualifiers: Other trials, Nusinersen naive, Pregnant, others

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

Compensation: Varies

Number of Visits: 2

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the body processes nusinersen, a treatment for spinal muscular atrophy (SMA), when delivered through a new device called the ThecaFlex DRx system compared to the traditional lumbar puncture method. Researchers are particularly interested in measuring the amount of nusinersen in the blood after these treatments. Participants currently receiving regular nusinersen treatments and part of the PIERRE study are good candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you must be on a regular maintenance dose of nusinersen to participate.

What prior data suggests that the ThecaFlex DRx system is safe for delivering nusinersen?

Previous studies have shown that nusinersen is safe for patients with spinal muscular atrophy (SMA). Common side effects include colds, fever, constipation, headache, vomiting, and back pain, which are usually mild and manageable. Long-term research indicates that nusinersen is generally well-tolerated over time. Importantly, the FDA has already approved nusinersen for treating SMA, further confirming its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Nusinersen is unique because it uses a specialized delivery system called the ThecaFlex DRx System, which allows for more direct and potentially more efficient administration of the drug. Unlike traditional treatments for Spinal Muscular Atrophy (SMA), which often involve regular lumbar punctures, this system could reduce the discomfort and frequency of such procedures. Researchers are excited about this approach because it might improve the patient's experience and potentially enhance the drug's effectiveness by maintaining more consistent drug levels in the body.

What evidence suggests that the ThecaFlex DRx system is effective for delivering nusinersen for spinal muscular atrophy?

Studies have shown that nusinersen effectively treats spinal muscular atrophy (SMA). It helps many patients, including teenagers and adults, improve or maintain their mobility. Real-world evidence indicates that nusinersen benefits both children and adults, particularly young children with SMA type 1. In some studies, patients did not experience severe side effects, and none died during treatment. Overall, nusinersen offers a promising option for improving the quality of life for people with SMA. ^{3 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for both adults and children with Spinal Muscular Atrophy who are already on a regular nusinersen treatment every 4 months. They must be part of the PIERRE study, which involves an implantable device called ThecaFlex DRx System.

Inclusion Criteria

Participants must be enrolled in the PIERRE study to be eligible for enrolment in the PIERRE PK study

I am on a stable 4-month nusinersen treatment schedule.

Exclusion Criteria

I am taking nusinersen, but not at a 12 mg dose.

Participant is pregnant, currently breastfeeding, or intending to become pregnant during the study

Ongoing participation or participation within 6 months or 5 half-lives of the agent (whichever is longer) of enrolment in other interventional clinical trials for the treatment of SMA (except for the PIERRE study)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment - Lumbar Puncture

Participants receive a dose of nusinersen by lumbar puncture

1 day

1 visit (in-person)

Treatment - ThecaFlex DRx System

The ThecaFlex DRx system is implanted, and participants receive a dose of nusinersen via the system

1 day

1 visit (in-person)

Follow-up

Participants are monitored for nusinersen levels in the blood, with samples taken before and after each dose, up to 24 hours after dosing

5 months

What Are the Treatments Tested in This Trial?

Interventions

• Nusinersen

Trial Overview Researchers are testing how nusinersen is processed in the body when delivered through the ThecaFlex DRx System compared to traditional lumbar puncture. Participants will receive doses by both methods, with blood samples taken before and after dosing to measure levels.

How Is the Trial Designed?

Group I: Nusinersen Via LP and ThecaFlex DRx System Experimental Treatment 2 Interventions

Participants will receive a maintenance dose of nusinersen, 12 milligrams (mg) via LP in the PIERRE-PK study, followed by implantation of the ThecaFlex DRx System and the subsequent nusinersen 12 mg maintenance dose via the system in the PIERRE study.

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

Alcyone Therapeutics, Inc

Industry Sponsor

Trials

3

Recruited

110+

Published Research Related to This Trial

Nusinersen treatment in adults with 5q spinal muscular atrophy showed significant improvements in motor function, with mean Hammersmith Functional Motor Scale Expanded (HFMSE) scores increasing at 6, 10, and 14 months compared to baseline, indicating its efficacy in this population.

The treatment was generally safe, with common side effects including headache and back pain, but no serious adverse events were reported, suggesting that nusinersen can be a viable option for adults with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Hagenacker, T., Wurster, CD., Günther, R., et al.[2020]

Nusinersen, an intrathecal antisense oligonucleotide, significantly improved motor functions in a 45-year-old female patient with spinal muscular atrophy type 3 (SMA3) after 11 months of treatment, despite her long disease duration of 40 years.

After discontinuation of Nusinersen due to worsening anxiety, the patient experienced disease progression, indicating that while the treatment is effective, stopping it may lead to a return to the natural course of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Discontinuation of Nusinersen Treatment in Long-Standing SMA3. Hiebeler, M., Abicht, A., Reilich, P., et al.[2021]

In a review of 15 studies involving 967 children, Nusinersen was found to have a low rate of definite adverse events (0.57%) and a higher rate of probable adverse events (7.76%), indicating it is generally safe for treating spinal muscular atrophy.

Nusinersen significantly reduced the incidence of serious and fatal adverse events compared to placebo, suggesting it not only has a favorable safety profile but also contributes to better overall health outcomes in children and adolescents with spinal muscular atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in the treatment of spinal muscular atrophy in children and adolescents with nusinersen: A systematic review and meta-analysis. Zhong, ZJ., Zheng, PM., Dou, HH., et al.[2023]

In a study of 52 spinal muscular atrophy (SMA) patients receiving a total of 265 nusinersen injections, the complication rate was very low, with only 2.2% experiencing post-lumbar puncture headaches requiring treatment, indicating that the procedure is generally safe.

Different injection techniques, including CT-guided and fluoroscopy-guided methods, were successfully used, demonstrating that image-guided procedures can be effective and safe alternatives to surgical approaches for administering nusinersen in SMA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen injections in adults and children with spinal muscular atrophy: a single-center experience. Özütemiz, C., Karachunski, P., Nascene, DR.[2021]

Nusinersen has been found to be safe and effective for treating patients with spinal muscular atrophy (SMA) type I, including those with chronic respiratory failure on permanent ventilation, based on a study of seven patients followed for an average of 46.2 months.

The treatment led to significant improvements in neuromuscular function, with 100% of patients showing disease amelioration by the 58- and 74-month follow-ups, and no significant adverse effects were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen for Spinal Muscular Atrophy Type I with Chronic Respiratory Failure: A Retrospective Study in South Korea. Shin, HJ., Na, JH., Lee, H., et al.[2023]

In a study of 79 adult patients with spinal muscular atrophy (SMA), those treated with nusinersen showed significant improvements in motor function, particularly a 2-point increase in the Revised Upper Limb Module (RULM) after 6 months, compared to untreated patients.

After an average follow-up of 16 months, nusinersen was associated with meaningful improvements in various functional scales, with 64.1% of treated patients reporting improvement, although most patients experienced at least one mild adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen in adult patients with 5q spinal muscular atrophy: A multicenter observational cohorts' study. Vázquez-Costa, JF., Povedano, M., Nascimiento-Osorio, AE., et al.[2022]

In a study of 52 spinal muscular atrophy (SMA) patients treated with nusinersen, significant improvements in motor function were observed in pediatric patients with SMA types 1 and 2 after receiving the drug, particularly after four doses.

Nusinersen was found to be safe, with no new safety concerns reported during the administration of 437 doses; however, adult patients with SMA type 3 who started treatment after age 18 did not show significant improvements in motor performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Nusinersen in Type 1, 2 and 3 Spinal Muscular Atrophy: Croatian Real-World Data. Belančić, A., Strbad, T., Kučan Štiglić, M., et al.[2023]

In a study of 116 adult patients with spinal muscular atrophy (SMA), nusinersen treatment showed significant improvements in motor function for those with SMA3, with notable increases in the Hammersmith Functional Rating Scale Expanded (HFMSE) scores over time.

While patients with SMA2 did not show significant changes in motor function, there was a trend towards improvement in those with some baseline function, indicating that nusinersen may be more effective in earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3. Maggi, L., Bello, L., Bonanno, S., et al.[2021]

Nusinersen, an antisense drug designed to increase functional SMN protein levels, demonstrated acceptable safety and tolerability in a phase 2 study involving 20 infants with spinal muscular atrophy, with all participants experiencing adverse events deemed unrelated to the drug.

The 12 mg dose of nusinersen led to significant improvements in motor function and milestones, as well as increased SMN protein levels in the spinal cord, suggesting its efficacy in treating infantile-onset spinal muscular atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study. Finkel, RS., Chiriboga, CA., Vajsar, J., et al.[2022]

Nusinersen has strong evidence (Class I) for improving motor milestones and survival rates in infants with spinal muscular atrophy (SMA) when treatment starts before 7 months of age, showing it is effective in early intervention.

In children aged 2-12 years with later-onset SMA, nusinersen also demonstrates significant improvements in motor function compared to sham control, indicating its efficacy across different age groups and stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence in focus: Nusinersen use in spinal muscular atrophy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Michelson, D., Ciafaloni, E., Ashwal, S., et al.[2019]

Nusinersen has shown a favorable safety profile in treating 323 infants and children with symptomatic spinal muscular atrophy (SMA), with a lower incidence of serious adverse events (41%) compared to sham procedures (61%).

The most common adverse events associated with nusinersen were mild and included pyrexia and upper respiratory infections, indicating that while some side effects occurred, they were consistent with typical SMA symptoms and lumbar puncture procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Integrated Safety Analysis of Infants and Children with Symptomatic Spinal Muscular Atrophy (SMA) Treated with Nusinersen in Seven Clinical Trials. Darras, BT., Farrar, MA., Mercuri, E., et al.[2021]

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 study of 32 adult patients with spinal muscular atrophy (SMA) treated with nusinersen over a median follow-up of 17 months, 78% showed improvement in motor function as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE) or the 6-minute walk test (6MWT).

Patients with SMA type 3 experienced significant increases in HFMSE scores at each time point, while type 2 patients showed initial benefits but remained stable afterward, indicating that nusinersen can be effective in improving motor function in adults with SMA, particularly in those with type 3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nusinersen for adults with spinal muscular atrophy. Arslan, D., Inan, B., Kilinc, M., et al.[2023]

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. sciencedirect.com sciencedirect.com/science/article/pii/S0960896622000323

Evaluation of real-life outcome data of patients with spinal ... Nusinersen is an effective treatment of SMA in children and adults, especially in young children with SMA type 1. In our study, no patient died and side effects ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2839761

Comparative Clinical Outcomes of Nusinersen and Gene ... This comparative effectiveness study examines respiratory and nutritional support, motor function, and survival outcomes in a matched cohort ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11393259/

Effectiveness of Nusinersen in Adolescents and Adults with ... Our study showed that nusinersen can improve motor function or prevent motor function from getting worse in many teenagers and adults with SMA.

5. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-025-03603-9

Real-world analysis of the efficacy and safety of nusinersen in ... Among these, 4 type I SMA patients (33.3%), 13 type II SMA patients (50.0%), and 3 type III SMA patients (75.0%) showed clinical improvement.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK533983/

Summary of Safety Data from Long-Term Studies - NCBI - NIH To provide a summary of safety data from long-term studies of nusinersen in patients with spinal muscular atrophy (SMA).

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 ... In the 12 mg regimen the most common adverse events (AEs) were respiratory infection, fever, constipation, headache, vomiting and back pain. The ...

8. nature.com nature.com/articles/s41598-024-67627-0

Unveiling the adverse events of Nusinersen in spinal ... This study aims to collect and analyze adverse event (AE) reports related to Nusinersen from the FAERS database.

9. curesma.org curesma.org/new-higher-dose-nusinersen-shows-benefit-in-sma/

New Higher Dose Nusinersen Efficacy and Safety Data ... The investigational, higher dose regimen of nusinersen comprises a more rapid loading regimen, two 50 mg doses 14 days apart, and higher maintenance regimen, ...