Spinal Muscular Atrophy
Conditions
Interventions
- Part A: Participants with later-onset SMA will receive loading doses of 28 mg of nusinersen intrathecally on Days 1, 15 and 29 followed by maintenance doses of 28 mg on Days 149 and 269.
- Active C
Sponsors
Berger Zdenek
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A, B and C: - Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound heterozygote) Part A: - Onset of clinical signs and symptoms consistent with SMA at > 6 months (> 180 days) of age (i.e., later-onset SMA) - Age 2 to 1 week to 6 months (> 180 days) of age (later onset): * Age 2 to = 10 and = 18 years of age at Screening must be ambulatory - Currently on nusinersen treatment at the time of Screening, with the first dose being at least 1 year prior to Screening NOTE: Other protocol defined Inclusion criteria may apply.
Exclusion criteria
Exclusion criteria: Part A, B and C: - Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the Screening period - Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or of an implanted central nervous system (CNS) catheter - Hospitalization for surgery, pulmonary event, or nutritional support within 2 months prior to Screening or planned within 12 months after the participant's first dose Part A: - Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for > 6 hours during a 24-hour period, at Screening - Medical necessity for a gastric feeding tube - Treatment with an investigational drug given for the treatment of SMA, 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 any survival motor neuron-2 (SMN2)-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation Part B: - Treatment with an investigational drug given for the treatment of SMA, 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 any SMN2-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation - Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset): * Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for > 6 hours during a 24-hour period, at Screening * Medical necessity for a gastric feeding tube - Participants with SMA symptom onset <= 6 months (<= 180 days) of age (infantile onset): Signs or symptoms of SMA present at birth or within the first week after birth. Part C: - Concurrent or previous participation and/or administration of nusinersen in another clinical study NOTE: Other protocol defined Exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Part B Infantile-onset SMA: Change from Baseline in CHOP INTEND Total Score [Time Frame: Baseline up to Day 183] 2. Part A and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) 3. Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters 4. Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs) 5. Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs 6. Part A and C: Change from Baseline in Body Length/Height 7. Part C Infantile-onset SMA: Change from Baseline in Head Circumference 8. Part C Infantile-onset SMA: Change from Baseline in Chest Circumference 9. Part C Infantile-onset SMA: Change from Baseline in Arm Circumference 10. Part A and C Later-onset SMA: Change from Baseline in Ulnar Length 11. Part A and C: Ratio of Weight for Age 12. Part A and C: Ratio of Weight for Length 13. Part C: Ratio of Head-to-chest Circumference 14. Part A and C: Change from Baseline in Activated Partial Thromboplastin Time (aPTT) 15. Part A and C: Change from Baseline in Prothrombin Time (PT) 16. Part A and C: Change from Baseline in International Normalized Ratio (INR) 17. Part A and C: Change in Urine Total Protein 18. Part A and C: Change from Baseline in Neurological Examination Outcomes 19. Part A and C: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements 20. Part A and C: Percentage of Participants with a Postbaseline Corrected QT Interval Using Fridericia's Formula (QTcF) of > 500 millisecond (msec) and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of > 60 msec | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Part B Infantile-onset SMA: Percentage of Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestone Responders [Time Frame: Day 302] 2. Part B Infantile-onset SMA: Change from Baseline in HINE Section 2 Motor Milestones Total Score [Time Frame: Baseline up to Day 302] 3. Part B Infantile-onset SMA: Time to Permanent Ventilation Permanent ventilation is defined as tracheostomy or >= 16 hours of ventilation/day continuously for > 21 days in the absence of an acute reversible event. 4. Part B Infantile-onset SMA: Time to Death (Overall Survival) 5. Part A and Part B Later-onset SMA: Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score 6. Part A and Part B Later-onset SMA: Change from Baseline in Revised Upper Limb Module (RULM) Score 7. Part A and Part B Later-onset SMA: Total Number of New WHO Motor Milestones 8. Part A and Part B Later-onset SMA: Change from Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) 9. Part A and Part B Later-onset SMA: Change from Baseline in Pediatric Quality of Life Inventory(TM) (PedsQL) 10. Part B: Number of Participants with AEs and SAEs 11. Part B: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters 12. Part B: Number of Participants with Clinically Significant Shifts from Baseline in ECGs 13. Part B: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs 14. Part B: Change from Baseline in Body Length/Height 15. Part B Infantile-onset SMA: Change from Baseline in Head Circumference 16. Part B Infantile-onset SMA: Change from Baseline in Chest Circumference 17. Part B Infantile-onset SMA: Change from Baseline in Arm Circumference 18. Part B Later-onset SMA: Change from Baseline in Ulnar Length 19. Part B: Ratio of Weight for Age 20. Part B: Ratio of Weight for Length 21. Part B: Ratio of Head-to-chest Circumference 22. Part B: Change from Baseline in aPT | — |
Countries
Colombia, Estonia, Ireland, Japan, Latvia, Spain, Taiwan, United States
Contacts
Public ContactBiogen Japan Medical Information
Biogen Japan Ltd.
Outcome results
None listed