Nusinersen for SMA

(RESPOND Trial)

Recruiting at 28 trial locations

Overseen By Global Biogen Clinical Trial Center

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Biogen

Must not be taking: Investigational drugs, SMN2 modifiers

Disqualifiers: Prior nusinersen, Severe AEs, others

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

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: 17

Duration: 95 weeks

46 Participants Needed

Trial Summary

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.

Is Nusinersen generally safe for humans?

Nusinersen has been approved for treating spinal muscular atrophy (SMA) type I, and safety data for its use in patients, including those switching from other treatments, have been extensively described. This suggests that Nusinersen is generally considered safe for human use in the context of SMA treatment. ^{1 2 3 4 5}

What makes the drug Nusinersen unique for treating SMA?

Nusinersen is unique for treating spinal muscular atrophy (SMA) because it is an antisense oligonucleotide (a short DNA or RNA molecule) that specifically targets and modifies the SMN2 gene to increase the production of the SMN protein, which is crucial for motor neuron survival. This mechanism of action is different from other treatments that may not directly target the genetic cause of SMA. ^{6 7 8 9 10}

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 will focus on children under the age of 3 who were previously treated with the gene therapy onasemnogene abeparvovec but are still facing health challenges related to their disease. The main goal of the study is to learn about the effect nusinersen has on muscle and movement ability (motor function). The main question researchers want to answer is: - What score do participants have on the HINE Section 2 Motor Milestones test after treatment? The Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones is an assessment that tests movements in different positions. This includes grasping, kicking, head control, rolling, sitting, crawling, standing, and walking. Researchers will use a group of tests to study body movements, reflexes, balance, and coordination. They will also record if participants need help with breathing. Researchers will also learn more about the safety of nusinersen. They will check participants for adverse events and changes in vital signs, heart tests, and laboratory tests including blood and urine tests. The study will be done as follows: * Participants will be screened to check if they can join the study. * Each participant will receive 4 initial doses of 12 mg of nusinersen on Days 1, 15, 29, and 64 of the Treatment Period. Then, they will receive 12 mg doses once every 4 months. * The total number of doses of nusinersen will be 9. * 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 95 weeks (close to 2 years). * There will be a follow-up safety period that lasts about 4 months. * In total, participants will have up to 14 study visits. Participants will stay in the study for up to 115 weeks.

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

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.

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.

Timeline

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)

Treatment Details

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.

Participant Groups

Group I: Nusinersen 12 mg Experimental Treatment 1 Intervention

Participants will receive Nusinersen 12 milligrams (mg) via intrathecal (IT) injection as loading doses on Days 1, 15, 29, and 64 followed by maintenance doses, every 4 months, on Days 183, 302, 421, 540 and 659.

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

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel/Carboplatin in Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis. Langer, CJ., Gajra, A., Gridelli, C., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017-2021. Zhang, J., Luo, L., Long, E., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Switching therapies: safety profile of Onasemnogene abeparvovec-xioi in a SMA1 patient previously treated with Risdiplam. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel/Carboplatin in Vulnerable Populations With Advanced Non-Small Cell Lung Cancer: Pooled Analysis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Body Composition Adjusted Dosing of Gemcitabine-Nab-Paclitaxel in Pancreatic Cancer Does Not Predict Toxicity Compared to Body Surface Area Dosing. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017-2021. [2023]

5. Greece pubmed.ncbi.nlm.nih.gov

Management of peripheral neuropathy induced by nab-paclitaxel treatment for breast cancer. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Synthesis of 125I labeled N-succinimidyl p-iodobenzoate for use in radiolabeling antibodies. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Differential accumulation of iodine-123-iodobenzamide in melanotic and amelanotic melanoma metastases in vivo. [2016]

8. United States pubmed.ncbi.nlm.nih.gov

A radioiodinated bretylium analog as a potential agent for scanning the adrenal medulla. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Radioiodination of proteins using N-succinimidyl 4-hydroxy-3-iodobenzoate. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Monoclonal antibody F(ab')2 fragment labeled with N-succinimidyl 2,4-dimethoxy-3-halobenzoates: in vivo comparison of iodinated and astatinated fragments. [2019]