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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04089566
Registration number
NCT04089566
Ethics application status
Date submitted
11/09/2019
Date registered
13/09/2019
Titles & IDs
Public title
Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy
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Scientific title
Escalating Dose and Randomized, Controlled Study of Nusinersen (BIIB058) in Participants With Spinal Muscular Atrophy
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Secondary ID [1]
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2019-002663-10
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Secondary ID [2]
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232SM203
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Universal Trial Number (UTN)
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Trial acronym
DEVOTE
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Muscular Atrophy, Spinal
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Condition category
Condition code
Musculoskeletal
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Other muscular and skeletal disorders
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Neurological
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Other neurological disorders
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Nusinersen
Experimental: 28/28 Milligram (mg) Safety Group - 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 comparator: 12/12 mg Active Control Group - Part B: Participants with infantile- or later-onset SMA will receive loading doses of 12 mg of nusinersen intrathecally on Days 1, 15, 29, and 64 followed by maintenance doses of 12 mg on Days 183 and 279. Sham procedure will be administered on Day 135.
Experimental: 50/28 mg Active Treatment Group - Part B: Participants with infantile- or later-onset SMA will receive loading doses of 50 mg of nusinersen intrathecally on Days 1 and 15 followed by maintenance doses of 28 mg on Days 135 and 279. Sham procedure will be administered on Days 29, 64 and 183.
Experimental: 12/50/28 mg Titration Group - Part C: Participants who have been receiving the approved dose of 12 mg for at least 1 year prior to entry, will receive a single bolus dose of 50 mg of nusinersen intrathecally on Day 1 (4 months after their most recent maintenance dose of 12 mg) followed by maintenance doses of 28 mg on Days 121 and 241.
Treatment: Drugs: Nusinersen
Administered as specified in the treatment arm
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Part B Infantile-onset SMA: Change from Baseline in CHOP-INTEND Total Score for Nusinersen 50/28mg Treatment Group Versus CS3B Matched Sham Control Group
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Assessment method [1]
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The CHOP-INTEND test is designed to evaluate the motor skills of infants with significant motor weakness. It includes 16 items (capturing neck, trunk, and proximal and distal limb strength) structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4. The change from baseline in the CHOP-INTEND total score will be compared to the study CS3B (NCT02193074) matched sham control group.
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Timepoint [1]
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Baseline up to Day 183
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Primary outcome [2]
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Part A and C: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
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Assessment method [2]
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An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), 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, 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.
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Timepoint [2]
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Screening up to Day 389
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Primary outcome [3]
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Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters
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Assessment method [3]
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Timepoint [3]
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Screening up to Day 302
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Primary outcome [4]
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Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Electrocardiograms (ECGs)
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Assessment method [4]
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Timepoint [4]
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Screening up to Day 302
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Primary outcome [5]
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Part A and C: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs
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Assessment method [5]
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Timepoint [5]
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Screening up to Day 302
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Primary outcome [6]
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Part A and C: Change from Baseline in Body Length/Height
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Assessment method [6]
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Timepoint [6]
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Baseline up to Day 302
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Primary outcome [7]
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Part C Infantile-onset SMA: Change from Baseline in Head Circumference
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Assessment method [7]
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Timepoint [7]
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Baseline up to Day 302
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Primary outcome [8]
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Part C Infantile-onset SMA: Change from Baseline in Chest Circumference
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Assessment method [8]
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Timepoint [8]
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Baseline up to Day 302
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Primary outcome [9]
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Part C Infantile-onset SMA: Change from Baseline in Arm Circumference
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Assessment method [9]
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Timepoint [9]
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Baseline up to Day 302
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Primary outcome [10]
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Part A and C Later-onset SMA: Change from Baseline in Ulnar Length
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Assessment method [10]
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Timepoint [10]
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Baseline up to Day 302
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Primary outcome [11]
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Part A and C: Ratio of Weight for Age
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Assessment method [11]
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Timepoint [11]
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Baseline up to Day 302
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Primary outcome [12]
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Part A and C: Ratio of Weight for Length
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Assessment method [12]
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Timepoint [12]
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Baseline up to Day 302
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Primary outcome [13]
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Part C: Ratio of Head-to-chest Circumference
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Assessment method [13]
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Timepoint [13]
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Baseline up to Day 302
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Primary outcome [14]
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Part A and C: Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
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Assessment method [14]
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Timepoint [14]
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Baseline up to Day 269
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Primary outcome [15]
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Part A and C: Change from Baseline in Prothrombin Time (PT)
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Assessment method [15]
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Timepoint [15]
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Baseline up to Day 269
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Primary outcome [16]
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Part A and C: Change from Baseline in International Normalized Ratio (INR)
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Assessment method [16]
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Timepoint [16]
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Baseline up to Day 269
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Primary outcome [17]
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Part A and C: Change in Urine Total Protein
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Assessment method [17]
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Timepoint [17]
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Baseline up to Day 302
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Primary outcome [18]
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Part A and C: Change from Baseline in Neurological Examination Outcomes
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Assessment method [18]
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Timepoint [18]
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Baseline up to Day 302
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Primary outcome [19]
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Part A and C: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
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Assessment method [19]
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Timepoint [19]
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Baseline up to Day 302
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Primary outcome [20]
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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
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Assessment method [20]
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Timepoint [20]
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Baseline up to Day 302
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Secondary outcome [1]
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Part B Infantile-onset SMA: Percentage of Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestone Responders for Nusinersen 50/28mg Treatment Group Versus CS3B Matched Sham Control Group
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Assessment method [1]
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Section 2 of the HINE is used to assess motor milestones of the participants It is composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. The percentage of the HINE section 2 motor milestones responders will be compared to the study CS3B (NCT02193074) matched sham control group.
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Timepoint [1]
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Baseline up to Day 183
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Secondary outcome [2]
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Part B Infantile-onset SMA: Change from Baseline in HINE Section 2 Motor Milestones Total Score for Nusinersen 50/28mg Treatment Group Versus CS3B Matched Sham Control Group
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Assessment method [2]
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Section 2 of the HINE is used to assess motor milestones of the participants. It is composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. The change from baseline in the HINE section 2 motor milestones total score will be compared to the study CS3B (NCT02193074) matched sham control group.
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Timepoint [2]
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Baseline up to Day 183
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Secondary outcome [3]
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Part B Infantile-onset SMA: Change from Baseline in Plasma Concentration of Neurofilament Light Chain (NF-L) for Nusinersen 50/28mg Treatment Group Versus CS3B Matched Sham Control Group
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Assessment method [3]
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The change from baseline in the plasma concentration of NF-L will be compared to the study CS3B (NCT02193074) matched sham control group.
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Timepoint [3]
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Baseline up to Day 183
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Secondary outcome [4]
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Part B Infantile-onset SMA: Change from Baseline in CHOP-INTEND Total Score for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [4]
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0
The CHOP-INTEND test is designed to evaluate the motor skills of infants with significant motor weakness. It includes 16 items (capturing neck, trunk, and proximal and distal limb strength) structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4.
Query!
Timepoint [4]
0
0
Baseline up to Day 302
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Secondary outcome [5]
0
0
Part B Infantile-onset SMA: Change from Baseline in HINE Section 2 Motor Milestones Total Score for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [5]
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0
Section 2 of the HINE is used to assess motor milestones of the participants It is composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking.
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Timepoint [5]
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0
Baseline up to Day 302
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Secondary outcome [6]
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Part B Infantile-onset SMA: Change from Baseline in Plasma Concentration of NF-L for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [6]
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0
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Timepoint [6]
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Baseline up to Day 29
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Secondary outcome [7]
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Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for Nusinersen 50/28mg Treatment Group Versus CS3B Matched Sham Control Group
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Assessment method [7]
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Permanent ventilation is defined as tracheostomy or = 16 hours of ventilation/day continuously for \> 21 days in the absence of an acute reversible event. Time to death or permanent ventilation will be compared to the study CS3B (NCT02193074) matched sham control group.
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Timepoint [7]
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Screening up to Day 183
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Secondary outcome [8]
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Part B Infantile-onset SMA: Time to Death (Overall Survival) for Nusinersen 50/28mg Treatment Group Versus CS3B Matched Sham Control Group
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Assessment method [8]
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Time to death (overall survival) will be compared to the study CS3B (NCT02193074) matched sham control group.
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Timepoint [8]
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Screening up to Day 183
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Secondary outcome [9]
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Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [9]
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Permanent ventilation is defined as tracheostomy or = 16 hours of ventilation/day continuously for \> 21 days in the absence of an acute reversible event.
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Timepoint [9]
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Screening up to Day 399
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Secondary outcome [10]
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Part B Infantile-onset SMA: Time to Death (Overall Survival) for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [10]
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0
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Timepoint [10]
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Screening up to Day 399
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Secondary outcome [11]
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Part B Later-onset SMA: Change from Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Score for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [11]
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HFMSE scale is a tool to assess motor function in children with SMA. The original 20 item Hammersmith Functional Motor Scale was expanded to include 13 additional adapted items from the Gross Motor Function Measure to improve sensitivity for the higher functioning ambulant population.
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Timepoint [11]
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Baseline up to Day 302
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Secondary outcome [12]
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Part B Later-onset SMA: Change from Baseline in Revised Upper Limb Module (RULM) Score for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [12]
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The RULM is developed to assess upper limb functional abilities participants with SMA. This test consists of upper limb performance items that are reflective of activities of daily living.
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Timepoint [12]
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Baseline up to Day 302
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Secondary outcome [13]
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Part B Later-onset SMA: Total Number of New World Health Organization (WHO) Motor Milestones for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [13]
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Timepoint [13]
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Baseline up to Day 302
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Secondary outcome [14]
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Part B Later-onset SMA: Change from Baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [14]
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ACEND is designed to quantify the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases. It includes domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance).
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Timepoint [14]
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Baseline up to Day 302
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Secondary outcome [15]
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Part B Later-onset SMA: Change from Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [15]
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PedsQL is used to measure health related quality of life (HRQOL) in children and adolescents. The PedsQL Measurement 4.0 Generic Core Scales include assessment of physical functioning, emotional functioning, social functioning, and school functioning and the PedsQL 3.0 Neuromuscular Module measures HRQOL.
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Timepoint [15]
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Baseline up to Day 302
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Secondary outcome [16]
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Part B Later-onset SMA: Change from Baseline in Cerebral Spinal Fluid (CSF) Concentration of NF-L for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [16]
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0
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Timepoint [16]
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Baseline up to Day 302
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Secondary outcome [17]
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Part B Later-onset SMA: Change from Baseline in Plasma Concentration of NF-L for Nusinersen 50/28mg Treatment Group Versus 12/12mg Active Control Group
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Assessment method [17]
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0
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Timepoint [17]
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Baseline up to Day 302
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Secondary outcome [18]
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Part B: Number of Participants with AEs and SAEs
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Assessment method [18]
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0
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal assessment such as an abnormal laboratory value), 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, 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.
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Timepoint [18]
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0
Screening up to Day 399
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Secondary outcome [19]
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Part B: Number of Participants with Clinically Significant Shifts from Baseline in Clinical Laboratory Parameters
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Assessment method [19]
0
0
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Timepoint [19]
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Screening up to Day 302
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Secondary outcome [20]
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Part B: Number of Participants with Clinically Significant Shifts from Baseline in ECGs
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Assessment method [20]
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0
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Timepoint [20]
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Day 1 up to Day 302
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Secondary outcome [21]
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Part B: Number of Participants with Clinically Significant Shifts from Baseline in Vital Signs
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Assessment method [21]
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0
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Timepoint [21]
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Screening up to Day 302
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Secondary outcome [22]
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Part B: Change from Baseline in Body Length/Height
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Assessment method [22]
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Timepoint [22]
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Baseline up to Day 302
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Secondary outcome [23]
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Part B Infantile-onset SMA: Change from Baseline in Head Circumference
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Assessment method [23]
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0
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Timepoint [23]
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Baseline up to Day 302
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Secondary outcome [24]
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Part B Infantile-onset SMA: Change from Baseline in Chest Circumference
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Assessment method [24]
0
0
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Timepoint [24]
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0
Baseline up to Day 302
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Secondary outcome [25]
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0
Part B Infantile-onset SMA: Change from Baseline in Arm Circumference
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Assessment method [25]
0
0
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Timepoint [25]
0
0
Baseline up to Day 302
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Secondary outcome [26]
0
0
Part B Later-onset SMA: Change from Baseline in Ulnar Length
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Assessment method [26]
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0
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Timepoint [26]
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Baseline up to Day 302
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Secondary outcome [27]
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Part B: Ratio of Weight for Age
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Assessment method [27]
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0
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Timepoint [27]
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Baseline up to Day 302
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Secondary outcome [28]
0
0
Part B: Ratio of Weight for Length
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Assessment method [28]
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0
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Timepoint [28]
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Baseline up to Day 302
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Secondary outcome [29]
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0
Part B: Ratio of Head-to-chest Circumference
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Assessment method [29]
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0
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Timepoint [29]
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Baseline up to Day 302
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Secondary outcome [30]
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0
Part B: Change from Baseline in aPTT
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Assessment method [30]
0
0
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Timepoint [30]
0
0
Baseline up to Day 279
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Secondary outcome [31]
0
0
Part B: Change from Baseline in PT
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Assessment method [31]
0
0
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Timepoint [31]
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0
Baseline up to Day 279
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Secondary outcome [32]
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Part B: Change from Baseline in INR
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Assessment method [32]
0
0
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Timepoint [32]
0
0
Baseline up to Day 279
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Secondary outcome [33]
0
0
Part B: Change in Urine Total Protein
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Assessment method [33]
0
0
Query!
Timepoint [33]
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0
Baseline up to Day 302
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Secondary outcome [34]
0
0
Part B: Change from Baseline in Neurological Examination Outcomes
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Assessment method [34]
0
0
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Timepoint [34]
0
0
Baseline up to Day 302
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Secondary outcome [35]
0
0
Part B: Percentage of Participants with a Postbaseline Platelet Count Below the Lower Limit of Normal on at least 2 Consecutive Measurements
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Assessment method [35]
0
0
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Timepoint [35]
0
0
Baseline up to Day 302
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Secondary outcome [36]
0
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Part B: Percentage of Participants with a Postbaseline QTcF of > 500 msec and an Increase from Baseline to Any Postbaseline Timepoint in QTcF of > 60 msec
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Assessment method [36]
0
0
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Timepoint [36]
0
0
Baseline up to Day 302
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Secondary outcome [37]
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Part A, B and C: Number of Hospitalizations
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Assessment method [37]
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0
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Timepoint [37]
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Day 1 to Day 302
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Secondary outcome [38]
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Part A, B and C: Duration of Hospitalizations
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Assessment method [38]
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0
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Timepoint [38]
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Day 1 to Day 302
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Secondary outcome [39]
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0
Part A, B and C: Clinical Global Impression of Change (CGIC)
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Assessment method [39]
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0
The CGIC scale is a 7 point scale that requires the clinician to assess how much the participant's illness has changed relative to a baseline state at the beginning of the intervention, where 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. Higher rating will indicate worsening of the condition.
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Timepoint [39]
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0
Day 302
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Secondary outcome [40]
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Part A, B and C: Number of Participants with Serious Respiratory Events
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Assessment method [40]
0
0
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Timepoint [40]
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0
Screening up to Day 399
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Secondary outcome [41]
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Part B Infantile-onset SMA: Percentage of Time on Ventilation
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Assessment method [41]
0
0
Query!
Timepoint [41]
0
0
Screening up to Day 302
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Secondary outcome [42]
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0
Parts A, B and C: Ventilator Use
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Assessment method [42]
0
0
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Timepoint [42]
0
0
Screening up to Day 302
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Secondary outcome [43]
0
0
Parts A and B: Change from Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale
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Assessment method [43]
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PASA questionnaire is developed to assess the signs and symptoms of dysphagia. It includes 33 items across 4 domains. General feeding, drinking liquids and eating solid foods will be assessed with 5 levels of response (Never, Rarely, Sometimes, Often, and Always), and 2 items will be assessed with 'Yes'/'No'. The assessment of swallowing concerns has 4 levels of response: Strongly Agree, Agree, Disagree, and Strongly Disagree. For Part A, it will be assessed in participants with later-onset SMA and in Part B, it will be assessed in participants with infantile- and later-onset SMA.
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Timepoint [43]
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0
Baseline up to Day 302
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Secondary outcome [44]
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0
Part B: Infantile SMA-onset: Change from baseline in CSF concentration of NF-L
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Assessment method [44]
0
0
Query!
Timepoint [44]
0
0
Baseline up to Day 302
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Secondary outcome [45]
0
0
Part A and C: Change from Baseline in HFMSE Score
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Assessment method [45]
0
0
HFMSE scale is a tool to assess motor function in children with SMA. The original 20 item Hammersmith Functional Motor Scale was expanded to include 13 additional adapted items from the Gross Motor Function Measure to improve sensitivity for the higher functioning ambulant population.
Query!
Timepoint [45]
0
0
Baseline up to Day 302
Query!
Secondary outcome [46]
0
0
Part A and C: Change from Baseline in RULM Score
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Assessment method [46]
0
0
The RULM is developed to assess upper limb functional abilities participants with SMA. This test consists of upper limb performance items that are reflective of activities of daily living.
Query!
Timepoint [46]
0
0
Baseline up to Day 302
Query!
Secondary outcome [47]
0
0
Part A and C: Total Number of New WHO Motor Milestones
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Assessment method [47]
0
0
Query!
Timepoint [47]
0
0
Baseline up to Day 302
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Secondary outcome [48]
0
0
Part A and C: Change from Baseline in ACEND
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Assessment method [48]
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0
ACEND is designed to quantify the caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases. It includes domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance).
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Timepoint [48]
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0
Baseline up to Day 302
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Secondary outcome [49]
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Part A and C: Change from Baseline in PedsQL™
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Assessment method [49]
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PedsQL is used to measure healthrelated quality of life (HRQOL) in children and adolescents. The PedsQL Measurement 4.0 Generic Core Scales include assessment of physical functioning, emotional functioning, social functioning, and school functioning and the PedsQL 3.0 Neuromuscular Module measures HRQOL.
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Timepoint [49]
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0
Baseline up to Day 302
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Secondary outcome [50]
0
0
Part C: Change from Baseline in CHOP-INTEND Total Score
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Assessment method [50]
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The CHOP-INTEND test is designed to evaluate the motor skills of infants with significant motor weakness. It includes 16 items (capturing neck, trunk, and proximal and distal limb strength) structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4.
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Timepoint [50]
0
0
Baseline to up Day 302
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Secondary outcome [51]
0
0
Part C: Change from Baseline in HINE Section 2 Motor Milestones Total Score
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Assessment method [51]
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Section 2 of the HINE is used to assess motor milestones of the participants. It is composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking.
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Timepoint [51]
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0
Baseline up to Day 302
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Eligibility
Key inclusion criteria
Key
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 = 15 years, inclusive, at the time of informed consent
Part B:
* Participants with SMA symptom onset = 6 months (= 180 days) of age (infantile onset) should have age > 1 week to = 7 months (= 210 days) at the time of informed consent
* Participants with SMA symptom onset > 6 months (> 180 days) of age (later onset):
* Age 2 to < 10 years at the time of informed consent
* Can sit independently but has never had the ability to walk independently
* HFMSE score = 10 and = 54 at Screening
Part C:
- Currently on nusinersen treatment at the time of Screening, with the first dose being at least 1 year prior to Screening
Part C Cohort 1:
- Participants of any age (individuals =18 years of age at Screening must be ambulatory)
Part C Cohort 2:
* Participants =18 years of age at Screening (can be ambulatory or nonambulatory)
* HFMSE total score =4 points at Screening
* RULM entry item A score =3 points at Screening
Key
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Minimum age
7
Days
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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 gene (SMN2)-splicing modifier or gene therapy; or prior antisense oligonucleotide treatment, or cell transplantation
Part B:
* Treatment with an investigational drug including but not limited to 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
* Concomitant or previous administration of any SMN2-splicing modifier (excluding nusinersen) or gene therapy, either in a clinical study or as part of medical care.
* Concurrent or previous participation in any interventional investigational study for any other drug or device within 30 days or 5 half-lives of the agent, whichever is longer, prior to Screening
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
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Intervention assignment
Other
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
26/03/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
30/05/2024
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Sample size
Target
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Accrual to date
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Final
145
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
0
0
Royal Children's Hospital - Parkville
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Recruitment postcode(s) [1]
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0
3052 - Parkville
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Recruitment outside Australia
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0
0
United States of America
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0
0
California
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0
0
United States of America
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Colorado
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0
United States of America
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0
Illinois
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0
United States of America
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Maryland
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0
United States of America
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Massachusetts
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0
United States of America
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Tennessee
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0
United States of America
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Texas
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0
0
Brazil
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Minas Gerais
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Brazil
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Rio Grande Do Sul
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Brazil
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Sao Paulo
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Chile
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Santiago
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China
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Beijing
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China
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Chongqing
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China
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Guangzhou
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China
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Hunan
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China
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Shandong
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China
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Sichuan
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Colombia
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Bogota
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Colombia
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Medellin
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Estonia
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Tallinn
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France
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Haute Garonne
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France
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Hauts De Seine
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Germany
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Baden Wuerttemberg
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Germany
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Hessen
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Greece
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Athens
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Greece
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Thessaloniki
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Hungary
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Budapest
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Ireland
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Dublin
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Israel
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Petach-Tikva
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Israel
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Tel Aviv
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Italy
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Milano
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Italy
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0
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Roma
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0
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Japan
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Fukuoka-Ken
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Japan
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Hyogo-Ken
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Japan
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Tokyo-To
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Korea, Republic of
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Gyeongsangbuk-do
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Korea, Republic of
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Seoul
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Latvia
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Riga
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Lebanon
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Beirut
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Mexico
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Distrito Federal
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Mexico
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Jalisco
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Netherlands
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Utrecht
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Poland
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Gdansk
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Poland
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Warszawa
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Russian Federation
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Ekaterinburg
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Russian Federation
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Moskva
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Saudi Arabia
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Dammam
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Saudi Arabia
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Jeddah
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Saudi Arabia
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Riyadh
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Spain
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Barcelona
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Spain
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0
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Madrid
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Spain
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Valencia
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0
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Taiwan
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0
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Kaohsiung
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0
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Taiwan
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0
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Taipei
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0
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Turkey
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0
0
Antalya
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Country [59]
0
0
United Kingdom
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State/province [59]
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0
Greater London
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Biogen
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The primary objectives of this study are to examine the clinical efficacy of nusinersen administered intrathecally at higher doses to participants with spinal muscular atrophy (SMA), as measured by change in Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) total score (Part B); to examine the safety and tolerability of nusinersen administered intrathecally at higher doses to participants with SMA (Parts A and C). The secondary objectives of this study are to examine the clinical efficacy of nusinersen administered intrathecally at higher doses to participants with SMA (Parts A, B and C); to examine the effect of nusinersen administered intrathecally at higher doses to participants with SMA (Parts A and C); to examine the safety and tolerability of nusinersen administered intrathecally at higher doses to participants with SMA, to examine the effect of nusinersen administered intrathecally at higher doses compared to the currently approved dose in participants with SMA (Part B).
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Trial website
https://clinicaltrials.gov/study/NCT04089566
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Trial related presentations / publications
Finkel RS, Ryan MM, Pascual Pascual SI, Day JW, Mercuri E, De Vivo DC, Foster R, Montes J, Gurgel-Giannetti J, MacCannell D, Berger Z. Scientific rationale for a higher dose of nusinersen. Ann Clin Transl Neurol. 2022 Jun;9(6):819-829. doi: 10.1002/acn3.51562. Epub 2022 May 13.
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Public notes
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Contacts
Principal investigator
Name
0
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Medical Director
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Address
0
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Biogen
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Country
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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0
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Phone
0
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Fax
0
0
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Email
0
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: https://vivli.org/
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04089566