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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04729907
Registration number
NCT04729907
Ethics application status
Date submitted
11/12/2020
Date registered
29/01/2021
Date last updated
3/02/2025
Titles & IDs
Public title
A Study to Learn About the Long-Term Safety of Higher Doses of Nusinersen (BIIB058) Given as Injections to Participants With Spinal Muscular Atrophy (SMA) Who Took Part in an Earlier Nusinersen Trial (ONWARD)
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Scientific title
A Long-Term Extension Study of Nusinersen (BIIB058) Administered at Higher Doses in Participants With Spinal Muscular Atrophy Who Previously Participated in an Investigational Study With Nusinersen
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Secondary ID [1]
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2023-505637-27
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Secondary ID [2]
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232SM302
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Universal Trial Number (UTN)
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Trial acronym
ONWARD
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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(has expanded access)
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Description of intervention(s) / exposure
Treatment: Drugs - Nusinersen
Experimental: BIIB058 28 mg (Prior Maintenance Dose 28 mg) - Participants who received maintenance dose of 28 milligrams (mg) nusinersen in study 232SM203 (NCT04089566), will receive maintenance dose of 28 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 1921.
Experimental: BIIB058 50/28 mg (Prior Maintenance Dose 12 mg) - Participants who received maintenance dose of 12 mg nusinersen in study 232SM203 (NCT04089566), will receive loading dose of 50 mg nusinersen, by intrathecal injection, on Day 1, followed by maintenance dose of 28 mg nusinersen, by intrathecal injection, every 4 months, up to Day 1921.
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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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
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Assessment method [1]
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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, 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, or is a medically important event.
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Timepoint [1]
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Up to Day 1921
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Primary outcome [2]
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Change from Baseline in Growth Parameters
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Assessment method [2]
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Growth parameters will be assessed by measuring body length or height (if feasible and appropriate), ulnar length (all participants), and head circumference, chest circumference, and arm circumference (all participants 3 years of age and younger) in centimeters.
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Timepoint [2]
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Up to Day 1921
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Primary outcome [3]
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Number of Participants With Shifts from Baseline in Clinical Laboratory Parameters
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Assessment method [3]
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Timepoint [3]
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Up to Day 1921
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Primary outcome [4]
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Number of Participants With Shifts from Baseline in Electrocardiogram (ECG)
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Assessment method [4]
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Timepoint [4]
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Up to Day 1921
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Primary outcome [5]
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Number of Participants With Shifts from Baseline in Vital Signs
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Assessment method [5]
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Timepoint [5]
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Up to Day 1921
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Primary outcome [6]
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Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
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Assessment method [6]
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Timepoint [6]
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Up to Day 1921
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Primary outcome [7]
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Change from Baseline in Prothrombin Time (PT)
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Assessment method [7]
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Timepoint [7]
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Up to Day 1921
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Primary outcome [8]
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Change from Baseline in International Normalized Ratio (INR)
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Assessment method [8]
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Timepoint [8]
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Up to Day 1921
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Primary outcome [9]
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Change from Baseline in Urine Total Protein
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Assessment method [9]
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Timepoint [9]
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Up to Day 1921
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Primary outcome [10]
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Change from Baseline in Neurological Examination Outcomes for Participants =2 Years of Age
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Assessment method [10]
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For participants 2 years of age and younger, the Hammersmith Infant Neurological Exam (HINE) Sections 1 and 3 will be conducted. This standard examination (developed by \[Dubowitz and Dubowitz 1981\]) is a quantitative scorable method for assessing the neurological development of infants between 2 and 24 months of age. The examination includes assessment of cranial nerve functions, posture, movements, tone, and reflexes. The HINE Section 1 form utilized in ONWARD contains 26 items and the Section 3 form utilized contains 3 items. For HINE Section 1 items, each item is scored 0-3. For HINE Section 3 items, scoring is variable (1-4, 1-5, or 1-6). Higher scores indicate better neurological function.
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Timepoint [10]
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Up to Day 1921
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Primary outcome [11]
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Number of Participants with Change from Baseline in Neurological Examination Outcomes for Participants >2 Years of Age
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Assessment method [11]
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For all participants \>2 years of age, standard neurological examinations, which include assessments of mental status, level of consciousness, sensory function, motor function, cranial nerve function, and reflexes, will be conducted.
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Timepoint [11]
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Up to Day 1921
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Primary outcome [12]
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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 [12]
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Timepoint [12]
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Up to Day 1921
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Primary outcome [13]
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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 [13]
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Timepoint [13]
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Up toDay 1921
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Secondary outcome [1]
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Total Number of New World Health Organization (WHO) Motor Milestones
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Assessment method [1]
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Timepoint [1]
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Up to Day 1921
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Secondary outcome [2]
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Number of Participants Who Used Respiratory Support, by Type
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Assessment method [2]
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Timepoint [2]
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Up to Day 1921
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Secondary outcome [3]
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Number of Hours Per Day of Respiratory Support
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Assessment method [3]
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Timepoint [3]
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Up to Day 1921
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Secondary outcome [4]
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Number of Days That Respiratory Support Is Used
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Assessment method [4]
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Timepoint [4]
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Up to Day 1921
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Secondary outcome [5]
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Time to Death (Overall Survival)
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Assessment method [5]
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Timepoint [5]
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Up to Day 1921
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Secondary outcome [6]
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Change from Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Total Score
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Assessment method [6]
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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 total score ranges from 0-64, with higher scores depicting better response. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
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Timepoint [6]
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Up to Day 1921
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Secondary outcome [7]
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Change from Baseline in Hammersmith Infant Neurological Examination (HINE) Section 2 Motor Milestones
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Assessment method [7]
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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 (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3). Total HINE score is the sum of points from each item and can range from 0 to 26, with higher scores depicting better level of ability. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
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Timepoint [7]
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Up to Day 1921
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Secondary outcome [8]
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Percentage of HINE Section 2 Motor Milestone Responders
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Assessment method [8]
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Section 2 of HINE is used to assess motor milestones of participants. It is composed of 8 motor milestone categories: voluntary grasp (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3). Total HINE score is sum of points from each item and can range from 0 to 26, with higher scores depicting better level of ability. HINE section 2 motor milestone responder is participant who demonstrates at least 2-point increase in category of ability to kick or increase to maximal score on that category or 1-point increase in motor milestones category of head control, rolling, sitting, crawling, standing, or walking, and among 7 motor milestone categories (excluding voluntary grasp), participant demonstrates improvement in more categories than worsening. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
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Timepoint [8]
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Up to Day 1921
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Secondary outcome [9]
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Percentage of Time Spent on Ventilation
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Assessment method [9]
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This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
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Timepoint [9]
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Up to Day 1921
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Secondary outcome [10]
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Time to Death or Permanent Ventilation
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Assessment method [10]
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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. This outcome measure will be assessed for participants who were evaluated with this measure in study 232SM203 (NCT04089566).
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Timepoint [10]
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Up to Day 1921
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Secondary outcome [11]
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Change from Baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) Score
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Assessment method [11]
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The HFMSE is a tool used to assess motor function in children with SMA. The original 20 item Hammersmith Functional Motor Scale (HFMS) was expanded to include 13 additional items to improve sensitivity for the higher functioning ambulant population. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all activities, with a maximum score of 66 with higher scores depicting better ability to perform activities. Participants = 2 years of age (at the time of the study visit) will be evaluated with HFMSE.
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Timepoint [11]
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Up to Day 1921
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Secondary outcome [12]
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Change from Baseline in Revised Upper Limb Module (RULM) Score
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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. The RULM is scored from 0 to 37 points, with higher scores indicating better function. Participants = 2 years of age (at the time of the study visit) will be evaluated with RULM.
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Timepoint [12]
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Up to Day 1921
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Secondary outcome [13]
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Change From Baseline in Plasma Levels of Neurofilament (NF)
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Assessment method [13]
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Timepoint [13]
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Up to Day 1921
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Eligibility
Key inclusion criteria
Key
* Completed the Day 302 visit in study 232SM203 (NCT04089566) in accordance with the study protocol
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Minimum age
2
Years
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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
* Treatment with another investigational therapy or enrollment in another interventional clinical study
* Treatment with an approved therapy for SMA after the Day 302 Visit of Study 232SM203 (NCT04089566)
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
Non-randomised 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
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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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
Active, not recruiting
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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
19/04/2021
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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
31/07/2026
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Actual
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Sample size
Target
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Accrual to date
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Final
115
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
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United States of America
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California
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United States of America
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Colorado
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United States of America
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Illinois
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Tennessee
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United States of America
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Texas
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Brazil
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Porto Alegre
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Brazil
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São Paulo
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Canada
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Ontario
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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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Guangdong
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China
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Zhejiang
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Colombia
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Bogota
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Estonia
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Tallinn
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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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Italy
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Milano
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Italy
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Roma
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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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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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Guadalajara
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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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State/province [31]
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Riyadh
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Valencia
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Taiwan
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Kaohsiung
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Taiwan
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Taipei
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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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Ethics approval
Ethics application status
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Summary
Brief summary
In this study, researchers will learn more about the use of nusinersen (BIIB058) in participants with spinal muscular atrophy (SMA). This study is an extension study and will enroll only those participants who have completed treatment in the parent study, 232SM203. The main goal of the study is to learn about the long-term safety of nusinersen. The main questions researchers want to answer are: * How many participants have adverse events and serious adverse events during the study? * How do the results of electrocardiograms (ECGs), vital signs, and laboratory tests including blood and urine tests change after treatment? * How many participants have a low platelet count after treatment? * How many participants had a change in the time it took for their heart to recharge between beats after treatment? * How does each participant's height and other measures of growth change after treatment? * How much do the results of neurological exams that check movement, reflexes, and brain function change after treatment? Researchers will also learn about the effect of nusinersen on mobility using various tests. They will study body movements, reflexes, balance, and coordination. They will also record if participants need help with breathing. The 232SM302 study will be done as follows: * Participants will be screened to check if they can join the study. * Participants will receive their 1st dose of nusinersen in this study about 4 months after their final dose in the parent study. * Each participant will receive nusinersen once every 4 months during the treatment period. * 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 64 months (1921 days). * There will be a follow-up safety period that lasts from 4 to 8 weeks. * In total, participants will have up to 19 study visits. Participants will stay in the study for close to 6 years.
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Trial website
https://clinicaltrials.gov/study/NCT04729907
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Trial related presentations / publications
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Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed
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Contacts
Principal investigator
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Medical Director
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Address
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Biogen
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Contact person for public queries
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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/NCT04729907
Download to PDF