ASCEND: A Study to Evaluate Higher Dose (HD) Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy Previously Treated With Risdiplam
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Higher Dose Nusinersen There will be two groups of participants previously treated with risdiplam in the study (nusinersen-naive group and nusinersen-experienced group), who 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. |
Drug: Nusinersen
Administered as specified in the treatment arm
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change in Total Revised Upper Limb Module (RULM) Score [Up to Day 855]
The RULM is being utilized to assess upper limb functional abilities of participants with SMA. This test consists of upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function.
Secondary Outcome Measures
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to Day 855]
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death or in the view of the investigator, places the participant at immediate risk of death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a birth defect, or is a medically important event.
- Number of Participants With Change from Baseline in Clinical Laboratory Parameters, Electrocardiogram (ECG), Vital Signs and Pulse Oximetry [Up to Day 855]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Genetic documentation of 5q SMA homozygous survival motor neuron-1 (SMN1) gene deletion or mutation or compound heterozygous mutation.
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Diagnosis of later-onset SMA with symptom onset at age >6 months.
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Aged ≥5 to ≤39 years at the time of informed consent for nusinersen-naïve participants.
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Aged ≥18 to ≤39 years at time of informed consent for nusinersen-experienced participants.
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Body weight >20 kg.
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Received oral risdiplam per the approved label or per the managed access program as follows Nusinersen-naive participants must have had prior treatment with risdiplam for ≥6 months and ≤12 months before enrollment.
Nusinersen-experienced participants must have stopped nusinersen for ≥16 months and have been on risdiplam for ≥12 months and ≤18 months before enrollment.
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Able to perform the age-appropriate functional assessments in the study.
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RULM entry item A score ≥3.
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RULM total score ≥5 and ≤30 at Screening.
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Nonambulatory, defined as not able to walk 15 feet (4.57 meters) independently without support.
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Willing to stop risdiplam treatment.
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Willing and able to start treatment with nusinersen.
Key Exclusion Criteria:
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Any major illness within 1 month before the Screening examination or within 1 week prior to Screening and up to first dose administration.
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Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening Period.
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Presence of an implanted shunt for the drainage of CSF or of an implanted central nervous system catheter.
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History of bacterial meningitis, viral encephalitis, or hydrocephalus.
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Ongoing medical condition that according to the Investigator would interfere with the conduct and assessments of the study. An example is a medical disability (e.g., wasting or cachexia, severe anemia, and respiratory parameters) that would interfere with the assessment of safety or would compromise the ability of the participant to undergo study procedures.
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Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
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Treatment with an investigational drug, biological agent, or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to Screening or anytime during the study; any prior or current treatment with gene therapy for the treatment of SMA.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arkansas Children's | Little Rock | Arkansas | United States | 72202 |
| 2 | Rare Disease Research, LLC | Atlanta | Georgia | United States | 30329 |
| 3 | Atrium Health Wake Forest Baptist | Winston-Salem | North Carolina | United States | 27101 |
| 4 | Research Site | Philadelphia | Pennsylvania | United States | 19104 |
| 5 | Children's Hospital of The King's Daughters | Norfolk | Virginia | United States | 23507 |
| 6 | Research Site | Milano | Italy | 20133 |
Sponsors and Collaborators
- Biogen
Investigators
- Study Director: Medical Director, Biogen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 232SM303
- 2021-001294-23