Muscular Atrophy, Spinal
Conditions
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).
Interventions
DRUGNusinersen
Administered as specified in the treatment arm
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
7 Days to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Part A, B and C: \- Genetic documentation of 5q SMA (homozygous gene deletion, mutation, or compound heterozygote) Part A: * Onset of clinical signs and symptoms consistent with SMA at \> 6 months (\> 180 days) of age (i.e., later-onset SMA) * Age 2 to ≤ 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
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | Baseline, Day 183 | The CHOP-INTEND test was designed to evaluate the motor skills of infants with significant motor weakness. It included 16 items (capturing neck, trunk, and proximal and distal limb strength), nine of which were scored 0, 1, 2, 3, or 4, five were scored as 0, 2, or 4, one was scored as 0, 1, 2, or 4, and one as 0, 2, 3, or 4 with higher scores indicating greater muscle strength and function. Total score was calculated as the sum of scores for each item. Total score ranged from 0 (worst possible score) and 64 (best possible score). The change from baseline to Day 183 in the CHOP-INTEND total score was compared to CS3B study (NCT02193074) sham control group using the joint-rank methodology to account for mortality. |
| Parts A and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | Part A: From the first dose of the study drug up to Day 389, Part C: From the first dose of the study drug up to Day 361 | An adverse event (AE) was any unfavorable & unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with use of an investigational product, whether or not related to investigational product. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of Investigator, placed participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. AE and SAEs were regarded as treatment-emergent if it was present prior to receiving first dose of nusinersen in this current study and subsequently worsened in severity or was not present prior to receiving first dose of nusinersen and subsequently appeared. |
| Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Parts A and C: Baseline up to Day 302 | Blood chemistry parameters included protein, albumin, creatinine, blood urea nitrogen, bilirubin (total and direct), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, calcium, phosphorus, bicarbonate, chloride, sodium, potassium, cystatin C, and creatine kinase. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported. |
| Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Parts A and C: Baseline up to Day 302 | Hematology parameters included complete blood cell count, with differential and platelet count, and absolute neutrophil count. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline values. The categories with at least one participant with shift from baseline in these parameters are reported. |
| Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Parts A and C: Baseline up to Day 302 | Urinalysis included assessments of urine total protein, specific gravity, pH, protein, glucose, ketones, bilirubin, blood, red blood cells (RBC), white blood cells (WBC), epithelial cells, bacteria, casts and crystals. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported. |
| Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Part A: Baseline up to Day 269, Part C: Baseline up to Day 241 | CSF parameters included cell count, total protein, and glucose. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported. |
| Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Parts A and C: Baseline up to Day 302 | The ECGs were assessed by the investigator to be normal, abnormal and abnormal AE. The number of participants with ECG shifts from normal to each of the categorical values denoting an abnormal scan (abnormal not AE, abnormal AE) was assessed. Shift from baseline to worst post-baseline values were reported. The categories with at least one participant with shift from baseline in ECG are reported. |
| Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Parts A and C: Baseline up to Day 302 | Vital sign assessment included temperature, pulse rate, systolic blood pressure, diastolic blood pressure, and respiratory rate. As pre-specified in protocol, the criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36.0 and \> 38.0 degrees Celsius (C), pulse rate \< 60 and \> 100 beats per minute (bpm), systolic blood pressure \[\< 90, \> 140 and \> 160 millimeters of mercury (mmHg)\], diastolic blood pressure \< 50, \> 90 and \> 100 mmHg and respiratory rate \< 12 and \> 20 breaths per minute. The categories with at least one participant with clinically relevant vital sign abnormalities are reported. |
| Parts A and C: Change From Baseline in Growth Parameters (Body Height) | Parts A and C: Baseline, Day 302 | — |
| Part C: Change From Baseline in Growth Parameters (Head Circumference) | Baseline, Day 302 | As pre-specified in the protocol, head circumference was measured for participants with infantile-onset SMA only. |
| Part C: Change From Baseline in Growth Parameters (Chest Circumference) | Baseline, Day 302 | As pre-specified in protocol, chest circumference was measured for participants with infantile-onset SMA only. |
| Part C: Change From Baseline in Growth Parameters (Arm Circumference) | Baseline, Day 302 | As pre-specified in the protocol, arm circumference was measured for participants with infantile-onset SMA. Here, negative change from baseline indicated reduction in arm circumference. |
| Parts A and C: Change From Baseline in Growth Parameters (Ulnar Length) | Parts A and C: Baseline, Day 302 | As pre-specified in the protocol, ulnar length was measured for participants with later-onset SMA. |
| Parts A and C: Change From Baseline in Growth Parameters (Weight for Age Percentile) | Parts A and C: Baseline, Day 302 | World Health Organization (WHO) child growth standards (2006) was used to calculate the weight for age percentile in the infantile-onset participants while the 2000 Centers for Disease Control and Prevention (CDC) Growth Charts was used to calculate the weight for age percentile for later-onset participants. Negative change from baseline indicates low weight for age percentile. |
| Part C: Change From Baseline in Growth Parameters (Weight for Length Ratio) | Baseline, Day 302 | As pre-specified in the protocol, weight for length ratio was assessed only for the participants with infantile-onset SMA. |
| Part C: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio) | Baseline, Day 302 | As pre-specified in the protocol, head to chest circumference ratio was assessed only for the participants with infantile-onset SMA. |
| Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Activated Partial Thromboplastin Time (aPTT)) | Parts A and C: Baseline up to Day 269 | Activated partial thromboplastin time was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of aPTT at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of aPTT at baseline to high values postbaseline. |
| Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Prothrombin Time (PT)) | Parts A and C: Baseline up to Day 269 | Prothrombin time was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of PT at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of PT at baseline to high values postbaseline. |
| Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (International Normalized Ratio (INR)) | Parts A and C: Baseline up to Day 269 | INR was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of INR at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of INR at baseline to high values postbaseline. The category with at least one participant with shift from baseline in INR ratio is reported. |
| Parts A and C: Change From Baseline in Urine Total Protein | Parts A and C: Baseline, Day 302 | — |
| Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Parts A and C: Baseline up to Day 302 | Participants with abnormalities in neurological examinations recorded as AEs were reported. |
| Parts A and C: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements | Parts A and C: Baseline up to Day 302 | — |
| Parts 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 | Parts A and C: Baseline up to Day 302 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Baseline up to Day 302 | Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. As pre-specified in protocol, the criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36.0 and \> 38.0 degrees C, pulse rate \< 60 and \> 100 bpm, systolic blood pressure \< 90, \> 140 and \> 160 mmHg, diastolic blood pressure \< 50, \> 90 and \> 100 mmHg and respiratory rate \< 12 and \> 20 breaths per minute. The categories with at least one participant with clinically relevant vital sign abnormalities are reported. |
| Part B: Change From Baseline in Growth Parameters (Body Height) | Baseline, Day 302 | Body height was measured for all participants (infantile-onset and later-onset SMA). |
| Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Head Circumference) | Baseline, Day 302 | Head circumference was measured in participants with infantile-onset SMA. |
| Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Chest Circumference) | Baseline, Day 302 | Chest circumference was measured in participants with infantile-onset SMA. |
| Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Arm Circumference) | Baseline, Day 302 | Arm circumference was measured in participants with infantile-onset SMA. |
| Part B: Change From Baseline in Growth Parameters (Ulnar Length) | Baseline, Day 302 | Ulnar length was measured in participants with later-onset SMA. |
| Part B: Change From Baseline in Growth Parameters (Weight for Age Percentile) | Baseline, Day 302 | WHO child growth standards (2006) was used to calculate the weight for age percentile in the infantile-onset participants. The 2000 CDC Growth Charts was used to calculate the weight for age percentile for later-onset participants. Negative change from baseline indicates reduction in weight for age percentile |
| Part B: Change From Baseline in Growth Parameters (Weight for Length Percentile) | Baseline, Day 302 | As pre-specified in the protocol, weight for length percentile was assessed only for the participants with infantile-onset SMA. Negative change from baseline indicates reduction in weight for length percentile. |
| Part B: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio) | Baseline, Day 302 | As pre-specified in the protocol, head to chest circumference ratio was assessed only for the participants with infantile-onset SMA. Negative change from baseline indicates reduction in head-to-chest circumference ratio. |
| Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Baseline up to Day 279 | aPTT was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of aPTT at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of aPTT at baseline to high values postbaseline. |
| Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Baseline up to Day 279 | Prothrombin time was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of PT at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of PT at baseline to high values postbaseline. |
| Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Baseline up to Day 279 | INR was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of INR at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of INR at baseline to high values postbaseline. |
| Part B: Change From Baseline in Urine Total Protein | Baseline, Day 302 | — |
| Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Baseline up to Day 302 | Participants with abnormalities in neurological examinations recorded as AEs were reported. |
| Part B: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements | Baseline up to Day 302 | — |
| 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 | Baseline up to Day 302 | — |
| Parts A, B and C: Number of Participants With Hospitalizations | Parts A, B, and C: Baseline up to Day 302 | — |
| Parts A, B and C: Percentage of Time of Hospitalization | Parts A, B, and C: Baseline up to Day 302 | — |
| Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | Parts A, B, and C: Day 302 | The CGIC scale was a 7 point scale that required the clinician to assess how much the participant's illness had 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 indicates worsening of the condition. A separate CGIC assessment was performed by the Investigator (I) and caregiver (C). The categories with at least one participant having a CGIC score was reported. |
| Parts A, B and C: Number of Serious Respiratory Events | Parts A, B, and C: Baseline up to Day 399 | — |
| Part B Infantile-onset SMA: Percentage of Time on Ventilation | Baseline up to Day 302 | — |
| Parts A, B and C: Number of Participants With Ventilator Use | Parts A, B, and C: Screening up to Day 302 | — |
| Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Baseline, Day 302 | PASA was assessed using a questionnaire. Caregivers were asked a series of questions regarding the mealtime behavior of the participant. The PASA questionnaire was developed to assess the signs and symptoms of dysphagia. It included 33 items across 4 domains: general feeding, drinking liquids, eating solid foods, & assessment of swallowing concerns. Items in domains general feeding, drinking liquids, & eating solid foods are assessed with 5 levels of response scored as 4-Never, 3-Rarely, 2-Sometimes, 1-Often, & 0-Always. Domain for assessing swallowing concerns has 4 levels of responses scored as: 3-Strongly Disagree, 2-Disagree, 1-Agree, 0-Strongly Agree. Higher score= improvement. A negative change from baseline=decrease in swallowing ability. From domains 'drinking liquids' and 'eating solid foods', 2 items (attempted to drink liquids and eat solid foods) were assessed as Yes/No, which are reported in another outcome measure. |
| Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Baseline, Day 302 | PASA was assessed using a questionnaire. Caregivers were asked a series of questions regarding the mealtime behavior of the participant. The PASA questionnaire was developed to assess the signs and symptoms of dysphagia. It included 33 items across 4 domains that cover general feeding, drinking liquids, eating solid foods, and assessment of swallowing concerns. The 2 items of domains drinking liquids (attempted to drink liquids), eating solid foods (attempted to eat solid foods) were assessed as Yes/No. Data for the 2 items were summarized in terms of the shift from baseline. |
| Part B: Change From Baseline in the PASA Scale | Baseline, Day 302 | PASA was assessed using a questionnaire. Caregivers were asked a series of questions regarding the mealtime behavior of the participant. The PASA questionnaire was developed to assess the signs and symptoms of dysphagia. It included 33 items across 4 domains that cover general feeding, drinking liquids, eating solid foods, and assessment of swallowing concerns. Items in domains of general feeding, drinking liquids, & eating solid foods are assessed with 5 levels of response scored as 4-Never, 3-Rarely, 2-Sometimes, 1-Often, & 0-Always. Domain for assessing swallowing concerns has 4 levels of responses scored as: 3-Strongly Disagree, 2-Disagree, 1-Agree, 0-Strongly Agree. Higher score= improvement. A negative change from baseline=decrease in swallowing ability. As planned, for part B of the study, the PASA scale was assessed for the domain general feeding only. |
| 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 | Baseline, Day 183 | Section 2 of HINE was used to assess motor milestones of participants. It's composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, & walking. Motor milestone responder: (i) a participant that demonstrated at least a 2-point increase in category of ability to kick or maximal score on that category or a 1-point increase in category of head control, rolling, sitting, crawling, standing, or walking, (ii) improvement in more categories than worsening, excluding category of voluntary grasp. For category of ability to kick, improvement, as defined in (i), worsening: at least a 2-point decrease or decrease to lowest possible score of no kicking. For other 6 categories, improvement: 1-point increase, worsening: at least 1-point decrease. Participants who died or withdrew from study were considered as non-responders. Difference in percentage of responders reported using Fisher's exact test. |
| Parts A and C: Change From Baseline in HFMSE Total Score | Parts A and C: Baseline, Day 302 | HFMSE scale was a tool used 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. Each item is scored 0 (unable), 1 (performs with modification or adaptation) or 2 (able) and the total score was calculated by summing the 33 items and ranged from 0 to 66 with higher scores indicating greater motor function. Negative change from baseline indicates decrease in motor function. |
| Parts A and C: Change From Baseline in RULM Total Score | Parts A and C: Baseline, Day 302 | RULM test was developed to assess upper limb functional abilities. RULM test: total 20 items. First item was assessed on 7-point scale (0:No useful function to 6-Can abduct both arms simultaneously, elbows in extension in full circle until they touch above head). This first item did not contribute to total score. For remaining 19 items, 18 items were assessed on 3-point scale: 0-Unable to achieve independently; 1-Modified method but achieves goal independent of physical assistance from another person; 2-Normal -achieves goal without any assistance. One remaining item was assessed as either 0 or 1. For each item, score was collected on left & right side. Derived total score=summing scores from these 19 individual items ranging from 0-if participant fails all activities to 37-if participant achieves all activities. If, for an individual item, response was recorded for both left & right side, highest score was used in calculating total score. Higher scores=increased upper limb function. |
| Parts A and C: Number of Participants With WHO Motor Milestones Status | Parts A and C: Baseline up to Day 302 | The WHO motor milestones were a set of six milestones in motor development: sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone and walking alone. The examiner recorded an overall rating of the participant's emotional state and then for each milestone one of the following four classifications: no (inability) - child tried but failed to perform the milestone, no (refusal) - child refused to perform despite being calm and alert, yes - child was able to perform the milestone, unable to test - could not be tested because of irritability, drowsiness or sickness. |
| Parts A and C: Change From Baseline in ACEND Total Score | Parts A and C: Baseline, Day 302 | ACEND instrument was designed to quantify caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA. The ACEND included a total of seven domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance, and each domain comprised several items. The total score for each domain was calculated on a scale of 0 to 100, with a higher score indicating a decreased caregiver burden. A negative change from baseline indicates an increased caregiver burden. |
| Parts A and C: Change From Baseline in PedsQL™ Total Score | Parts A and C: Baseline, Day 302 | Participants were evaluated using PedsQL generic core scale & neuromuscular module. PedsQL generic core scale was used to calculate PedsQL inventory total score (PQLI), that included parent & participant's assessment on 4 dimensions: physical, emotional, social, & school functioning & psychosocial health. Each item was scored on 5-point ordinal scale (0=never to 4=almost always). PedsQL neuromuscular module (PQLN) measured HRQOL dimensions specific to with neuromuscular disorders, like SMA. Each item was scored on 5-point ordinal scale (0=never to 4=almost always). Dimensions were reversed scored & were linearly transformed to 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0) for both PQLI and PQLN, higher scores indicative of better health related quality of life. Total scale scores were calculated as sum of all items over number of items answered on all scales. If more than 50% of items/more within a dimension were missing, scale score was not computed. |
| Part C: Change From Baseline in CHOP-INTEND Total Score | Baseline, Day 302 | The CHOP-INTEND test was designed to evaluate the motor skills of infants with significant motor weakness. It included 16 items (capturing neck, trunk, and proximal and distal limb strength), nine of which were scored 0, 1, 2, 3, or 4, five were scored as 0, 2, or 4, one was scored as 0, 1, 2, or 4, and one as 0, 2, 3, or 4 with higher scores indicating greater muscle strength and function. Total score was calculated as the sum of scores for each item. Total score ranged from 0 (worst possible score) and 64 (best possible score). |
| Part C: Change From Baseline in HINE Section 2 Motor Milestones Total Score | Baseline, Day 302 | Section 2 of the HINE was used to assess motor milestones of the infantile-onset SMA participants. It's composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. Within each of these categories, participants can progress from complete absence of a motor ability (the lowest level in each category) through multiple milestones (2 to 4 levels in each category) to the highest level within the category. The 8 categories of HINE Section 2 can be summed to give a total score that ranges from 0 to 26. |
| Part B: Infantile SMA-onset: Change From (Ratio to) Baseline in CSF Concentration of NF-L | Baseline, Day 279 | The change from baseline data was reported in terms of geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline. |
| 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 | Baseline, Day 183 | Section 2 of the HINE was used to assess motor milestones of the participants. It's composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. Within each category, 3 to 5 levels can be achieved. The total HINE section 2 motor milestones score was calculated as sum of each level & ranged from 0 to 26, higher score indicating improvement in motor milestones. A negative change from baseline indicates decline in motor milestones. Change from baseline in HINE section 2 motor milestones total score was compared to study CS3B (NCT02193074) matched sham control group, and was analysed using joint rank methodology. |
| Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of Neurofilament Light Chain (NF-L) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | Baseline, Day 183 | The change from baseline in the plasma concentration of NF-L was compared to the study CS3B (NCT02193074) matched sham control group. Joint rank methodology was used for the analysis to account for mortality. The change from baseline data was reported in terms of least square geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline. |
| Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 302 | The CHOP-INTEND test was designed to evaluate the motor skills of infants with significant motor weakness. It included 16 items (capturing neck, trunk, and proximal and distal limb strength), nine of which were scored 0, 1, 2, 3, or 4, five were scored as 0, 2, or 4, one was scored as 0, 1, 2, or 4, and one as 0, 2, 3, or 4 with higher scores indicating greater muscle strength and function. Total score was calculated as the sum of scores for each item. Total score ranged from 0 (worst possible score) and 64 (best possible score). The change from baseline to Day 302 in the total score was analyzed using the joint-rank methodology to account for mortality. |
| Part B Infantile-onset SMA: Change From Baseline in HINE Section 2 Motor Milestones Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 302 | Section 2 of the HINE was used to assess motor milestones of the participants. It's composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. Within each of these categories, participants can progress from complete absence of a motor ability (the lowest level in each category) through multiple milestones (2 to 4 levels in each category) to the highest level within the category. The total motor milestones score for HINE section was calculated as the sum of each level and ranged from 0 to a maximum score of 26, higher score indicating improvement in motor milestones. |
| Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 64 | The change from baseline in plasma concentration of NF-L was analysed using the joint rank methodology to account for mortality. The change from baseline data was reported in terms of LS geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline. |
| Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | Screening up to Day 399 | Permanent ventilation was defined as tracheostomy or ≥ 16 hours of ventilation/day continuously for \> 21 days in absence of an acute reversible event. An independent endpoint adjudication committee (EAC) determined date at which a participant was considered to have met protocol-specified criteria of an acute reversible event. Only events that were adjudicated by the EAC as meeting the criteria for permanent ventilation or death were included in analysis. Participants who did not meet the endpoint definition were censored on the last occasion the participant was seen (either in-person visit or by telephone contact), irrespective of whether the participant has completed the full course of treatment and whether the participant has completed the study or permanently withdrawn. |
| Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | Screening up to Day 399 | Time to death was determined by an independent EAC. Time to death (overall survival) was compared to the study CS3B (NCT02193074) matched sham control group. |
| Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Screening up to Day 399 | Permanent ventilation was defined as tracheostomy or ≥ 16 hours of ventilation/day continuously for \> 21 days in the absence of an acute reversible event. An independent EAC determined the date at which a participant was considered to have met the protocol-specified criteria of an acute reversible event. Only events that were adjudicated by the EAC as meeting the protocol defined criteria for permanent ventilation or death was included in the analysis. Participants who did not meet the endpoint definition were censored on the last occasion the participant was seen (either in-person visit or by telephone contact), irrespective of whether the participant has completed the full course of treatment and whether the participant has completed the study or permanently withdrawn. |
| Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Screening up to Day 399 | Time to death was determined by an independent EAC. Participants who did not die were censored on the last occasion the participant was seen (either in-person visit or by telephone contact), irrespective of whether the participant has completed the full course of treatment and whether the participant has completed the study or permanently withdrawn. |
| Part B Later-onset SMA: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 302 | HFMSE scale was a tool used to assess motor function in children with later-onset 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. Each item is scored 0 (unable), 1 (performs with modification or adaptation) or 2 (able) and the total score was calculated by summing the 33 items and ranged from 0 to 66 with higher scores indicating greater motor function. |
| Part B Later-onset SMA: Change From Baseline in Revised Upper Limb Module (RULM) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 302 | RULM test was developed to assess upper limb functional abilities. RULM test: total 20 items. First item was assessed on 7-point scale (0:No useful function to 6-Can abduct both arms simultaneously, elbows in extension in full circle until they touch above head). This first item did not contribute to total score. For remaining 19 items, 18 items were assessed on 3-point scale: 0-Unable to achieve independently; 1-Modified method but achieves goal independent of physical assistance from another person; 2-Normal -achieves goal without any assistance. One remaining item was assessed as either 0 or 1. For each item, score was collected on left & right side. Derived total score=summing scores from these 19 individual items ranging from 0-if participant fails all activities to 37-if participant achieves all activities. If, for an individual item, response was recorded for both left & right side, highest score was used in calculating total score. Higher scores=increased upper limb function. |
| Part B Later-onset SMA: Number of New World Health Organization (WHO) Motor Milestones Achieved Per Participant for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 302 | The WHO motor milestones were a set of six milestones in motor development: sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone and walking alone. The examiner recorded an overall rating of the participant's emotional state and then for each milestone one of the following four classifications: no (inability) - child tried but failed to perform the milestone, no (refusal) - child refused to perform despite being calm and alert, yes - child was able to perform the milestone, unable to test - could not be tested because of irritability, drowsiness or sickness. Mean of number of new milestones achieved per participant was calculated and reported in this outcome measure. |
| Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 302 | ACEND instrument was designed to quantify caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA. The ACEND included a total of seven domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance, and each domain comprised several items. The total score for each domain was calculated on a scale of 0 to 100, with a higher score indicating a decreased caregiver burden. A negative change from baseline indicates an increased caregiver burden. |
| Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 302 | Participants were evaluated using PedsQL generic core scale & neuromuscular module. PedsQL generic core scale was used to calculate PedsQL inventory total score (PQLI), that included parent & participant's assessment on 4 dimensions: physical, emotional, social, & school functioning & psychosocial health. Each item was scored on 5-point ordinal scale (0=never to 4=almost always). PedsQL neuromuscular module (PQLN) measured HRQOL dimensions specific to with neuromuscular disorders, like SMA. Each item was scored on 5-point ordinal scale (0=never to 4=almost always). Dimensions were reversed scored & were linearly transformed to 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0) for both PQLI and PQLN, higher scores indicative of better health related quality of life. Total scale scores were calculated as sum of all items over number of items answered on all scales. If more than 50% of items/more within a dimension were missing, scale score was not computed. |
| Part B Later-onset SMA: Change From (Ratio to) Baseline in CSF Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 279 | The change from baseline data was reported in terms of geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline. |
| Part B Later-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Baseline, Day 302 | The change from baseline data was reported in terms of geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline. |
| Part B: Number of Participants With TEAEs and TESAEs | From the first dose of the study drug up to Day 399 | AE was 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 was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. AE was regarded as treatment-emergent if it was present prior to receiving the first dose of nusinersen in the current study and subsequently worsened in severity or was not present prior to receiving the first dose of nusinersen and subsequently appeared. |
| Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Baseline up to Day 302 | Hematology parameters included complete blood cell count, with differential and platelet count, and absolute neutrophil count. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported. |
| Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Baseline up to Day 302 | Blood chemistry parameters included protein, albumin, creatinine, blood urea nitrogen, bilirubin (total and direct), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, calcium, phosphorus, bicarbonate, chloride, sodium, potassium, cystatin C, and creatine kinase. Parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. Categories with at least one participant with shift from baseline in these parameters are reported. |
| Part B: Number of Participants With Shifts From Baseline in Urinalysis | Baseline up to Day 302 | Urinalysis included assessments of urine total protein, specific gravity, pH, protein, glucose, ketones, bilirubin, blood, RBC , WBC, epithelial cells, bacteria, casts and crystals. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high, positive, abnormal or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, negative, absent, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported. |
| Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Baseline up to Day 302 | CSF parameters included cell count, total protein, and glucose. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported. |
| Part B: Number of Participants With Shift From Baseline in ECGs | Baseline up to Day 302 | The ECGs were assessed by the investigator to be normal, abnormal and abnormal AE. The number of participants with ECG shifts from normal to each of the categorical values denoting an abnormal scan (abnormal not AE, abnormal AE) was assessed. Shift from baseline to worst post-baseline values were reported. The categories with at least one participant with shift from baseline in ECG are reported. |
Countries
Brazil, Canada, Chile, China, Colombia, Estonia, Germany, Hungary, Italy, Japan, Lebanon, Mexico, Poland, Russia, Saudi Arabia, Spain, Taiwan, United States
Participant flow
Recruitment details
Participants took part in the study at the investigative sites in the United States, Brazil, Canada, Chile, China, Colombia, Estonia, Germany, Hungary, Italy, Japan, Lebanon, Mexico, Poland, Russia, Saudi Arabia, Spain, and Taiwan.
Pre-assignment details
A total of 145 participants diagnosed with spinal muscular atrophy (SMA) were enrolled in the 3-parts (Parts A, B, and C). Of which, 117 of participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Part A: 28/28 mg Nusinersen Participants with later-onset SMA received 3 loading doses of 28 mg of nusinersen, IT, on Days 1, 15 and 29 followed by 2 maintenance doses of 28 mg on Days 149 and 269. | 6 |
| Part B: Infantile-Onset SMA: 12/12 mg Nusinersen Participants with infantile-onset SMA in the control group received 4 loading doses of 12 mg of nusinersen IT on Days 1, 15, 29, and 64 followed by 2 maintenance doses of 12 mg on Days 183 and 279. Sham procedure was administered on Day 135. | 25 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen Participants with infantile-onset SMA received 2 loading doses of 50 mg of nusinersen IT on Days 1 and 15 followed by 2 maintenance doses of 28 mg on Days 135 and 279. Sham procedure was administered on Days 29, 64 and 183. | 50 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen Participants with later-onset SMA in the control group received 4 loading doses of 12 mg of nusinersen IT on Days 1, 15, 29, and 64 followed by 2 maintenance doses of 12 mg on Days 183 and 279. Sham procedure was administered on Day 135. | 8 |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen Participants with later-onset SMA received 2 loading doses of 50 mg of nusinersen IT on Days 1 and 15 followed by 2 maintenance doses of 28 mg on Days 135 and 279. Sham procedure was administered on Days 29, 64 and 183. | 16 |
| Part C: 50/28 mg Nusinersen Participants with infantile and later-onset SMA who had been receiving the approved dose of 12 mg for at least 1 year prior to entry, received a single bolus dose of 50 mg of nusinersen IT on Day 1 (4 months after their most recent maintenance dose of 12 mg) followed by 2 maintenance doses of 28 mg on Days 121 and 241. | 40 |
| Total | 145 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 6 | 10 | 0 | 0 | 0 |
| Overall Study | Reason not Specified | 0 | 4 | 4 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Parent or Guardian | 0 | 2 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part C: 50/28 mg Nusinersen | Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Infantile-Onset SMA: 12/12 mg Nusinersen | Part A: 28/28 mg Nusinersen |
|---|---|---|---|---|---|---|---|
| Age, Customized Adolescents (12 - 17 years) | 7 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Customized Adults (18 - 64 years) | 23 Participants | 23 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Children (2 - 11 years) | 39 Participants | 10 Participants | 16 Participants | 8 Participants | 0 Participants | 0 Participants | 5 Participants |
| Age, Customized From 65 - 84 years | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days - 23 months) | 71 Participants | 0 Participants | 0 Participants | 0 Participants | 47 Participants | 24 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants |
| Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOPINTEND) Total Score | 20.6 Score on scale STANDARD_DEVIATION 9.98 | — | — | — | 20.9 Score on scale STANDARD_DEVIATION 10.23 | 19.9 Score on scale STANDARD_DEVIATION 9.63 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 5 Participants | 6 Participants | 2 Participants | 18 Participants | 10 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants | 35 Participants | 10 Participants | 6 Participants | 30 Participants | 13 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 30 Participants | 7 Participants | 5 Participants | 2 Participants | 10 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported Due to Confidentiality Regulations | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 17 Participants | 1 Participants | 2 Participants | 3 Participants | 7 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 93 Participants | 32 Participants | 8 Participants | 3 Participants | 29 Participants | 17 Participants | 4 Participants |
| Sex: Female, Male Female | 71 Participants | 15 Participants | 14 Participants | 6 Participants | 24 Participants | 11 Participants | 1 Participants |
| Sex: Female, Male Male | 74 Participants | 25 Participants | 2 Participants | 2 Participants | 26 Participants | 14 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 6 / 25 | 10 / 50 | 0 / 8 | 0 / 16 | 0 / 40 |
| other Total, other adverse events | 4 / 6 | 19 / 25 | 37 / 50 | 7 / 8 | 14 / 16 | 36 / 40 |
| serious Total, serious adverse events | 1 / 6 | 18 / 25 | 30 / 50 | 4 / 8 | 2 / 16 | 6 / 40 |
Outcome results
Primary
Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group
The CHOP-INTEND test was designed to evaluate the motor skills of infants with significant motor weakness. It included 16 items (capturing neck, trunk, and proximal and distal limb strength), nine of which were scored 0, 1, 2, 3, or 4, five were scored as 0, 2, or 4, one was scored as 0, 1, 2, or 4, and one as 0, 2, 3, or 4 with higher scores indicating greater muscle strength and function. Total score was calculated as the sum of scores for each item. Total score ranged from 0 (worst possible score) and 64 (best possible score). The change from baseline to Day 183 in the CHOP-INTEND total score was compared to CS3B study (NCT02193074) sham control group using the joint-rank methodology to account for mortality.
Time frame: Baseline, Day 183
Population: As planned, analysis was performed in the Matched sham set. Matched sham set comprised of sham control participants of the CS3B study (NCT02193074) identified by a matching algorithm and all of current study 50/28 mg participants that were included in the ITT set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | 42.9 score on scale |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | 16.9 score on scale |
p-value: <0.000195% CI: [17.941, 34.172]ANCOVA
Primary
Part C: Change From Baseline in Growth Parameters (Arm Circumference)
As pre-specified in the protocol, arm circumference was measured for participants with infantile-onset SMA. Here, negative change from baseline indicated reduction in arm circumference.
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part C: Change From Baseline in Growth Parameters (Arm Circumference) | -1.0 cm |
Primary
Part C: Change From Baseline in Growth Parameters (Chest Circumference)
As pre-specified in protocol, chest circumference was measured for participants with infantile-onset SMA only.
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part C: Change From Baseline in Growth Parameters (Chest Circumference) | 2.5 cm |
Primary
Part C: Change From Baseline in Growth Parameters (Head Circumference)
As pre-specified in the protocol, head circumference was measured for participants with infantile-onset SMA only.
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part C: Change From Baseline in Growth Parameters (Head Circumference) | 2.0 cm |
Primary
Part C: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio)
As pre-specified in the protocol, head to chest circumference ratio was assessed only for the participants with infantile-onset SMA.
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part C: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio) | 0.0 ratio |
Primary
Part C: Change From Baseline in Growth Parameters (Weight for Length Ratio)
As pre-specified in the protocol, weight for length ratio was assessed only for the participants with infantile-onset SMA.
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part C: Change From Baseline in Growth Parameters (Weight for Length Ratio) | 0.005 ratio |
Primary
Parts A and C: Change From Baseline in Growth Parameters (Body Height)
Time frame: Parts A and C: Baseline, Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in Growth Parameters (Body Height) | 7.2 centimeter (cm) | Standard Deviation 1.7 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in Growth Parameters (Body Height) | 0.8 centimeter (cm) | Standard Deviation 3.12 |
Primary
Parts A and C: Change From Baseline in Growth Parameters (Ulnar Length)
As pre-specified in the protocol, ulnar length was measured for participants with later-onset SMA.
Time frame: Parts A and C: Baseline, Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in Growth Parameters (Ulnar Length) | 1.8 cm | Standard Deviation 1.43 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in Growth Parameters (Ulnar Length) | 0.0 cm | Standard Deviation 1.27 |
Primary
Parts A and C: Change From Baseline in Growth Parameters (Weight for Age Percentile)
World Health Organization (WHO) child growth standards (2006) was used to calculate the weight for age percentile in the infantile-onset participants while the 2000 Centers for Disease Control and Prevention (CDC) Growth Charts was used to calculate the weight for age percentile for later-onset participants. Negative change from baseline indicates low weight for age percentile.
Time frame: Parts A and C: Baseline, Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in Growth Parameters (Weight for Age Percentile) | 12.2 percentile | Standard Deviation 12.84 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in Growth Parameters (Weight for Age Percentile) | -2.7 percentile | Standard Deviation 9.47 |
Primary
Parts A and C: Change From Baseline in Urine Total Protein
Time frame: Parts A and C: Baseline, Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in Urine Total Protein | 0.010 gram per litre (g/L) | Standard Deviation 0.1235 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in Urine Total Protein | -0.692 gram per litre (g/L) | Standard Deviation 3.704 |
Primary
Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters
Vital sign assessment included temperature, pulse rate, systolic blood pressure, diastolic blood pressure, and respiratory rate. As pre-specified in protocol, the criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36.0 and \> 38.0 degrees Celsius (C), pulse rate \< 60 and \> 100 beats per minute (bpm), systolic blood pressure \[\< 90, \> 140 and \> 160 millimeters of mercury (mmHg)\], diastolic blood pressure \< 50, \> 90 and \> 100 mmHg and respiratory rate \< 12 and \> 20 breaths per minute. The categories with at least one participant with clinically relevant vital sign abnormalities are reported.
Time frame: Parts A and C: Baseline up to Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse rate <60 bpm | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic blood pressure <50 mmHg | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic blood pressure <90 mmHg | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic blood pressure >90 mmHg | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse rate >100 bpm | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory rate <12 breaths/min | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic blood pressure >140 mmHg | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory rate >20 breaths/min | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature <36.0 C | 4 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory rate >20 breaths/min | 27 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature <36.0 C | 13 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse rate <60 bpm | 14 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse rate >100 bpm | 19 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic blood pressure <90 mmHg | 13 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic blood pressure >140 mmHg | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic blood pressure <50 mmHg | 7 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic blood pressure >90 mmHg | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory rate <12 breaths/min | 7 Participants |
Primary
Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs
Participants with abnormalities in neurological examinations recorded as AEs were reported.
Time frame: Parts A and C: Baseline up to Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Vestibular Disorder | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Asthenia | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Gait Disturbance | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Balance Disorder | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Disturbance in Attention | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Paraesthesia | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Disturbance in Attention | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Vestibular Disorder | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Balance Disorder | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Asthenia | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Paraesthesia | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Gait Disturbance | 1 Participants |
Primary
Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters
CSF parameters included cell count, total protein, and glucose. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.
Time frame: Part A: Baseline up to Day 269, Part C: Baseline up to Day 241
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Number analysed (n)' indicates the number of participants evaluable for the specified urinalysis parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Glucose Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Glucose Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Protein Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Protein Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Erythrocytes Shift to High | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Leukocytes Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Erythrocytes Shift to High | 8 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Glucose Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Protein Shift to High | 8 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Glucose Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Leukocytes Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Cerebrospinal Fluid (CSF) Parameters | Protein Shift to Low | 3 Participants |
Primary
Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)
Blood chemistry parameters included protein, albumin, creatinine, blood urea nitrogen, bilirubin (total and direct), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, calcium, phosphorus, bicarbonate, chloride, sodium, potassium, cystatin C, and creatine kinase. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.
Time frame: Parts A and C: Baseline up to Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. Number analyzed 'n' indicates the number of participants evaluable for analysis of the specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to High | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Aspartate Aminotransferase Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Indirect Bilirubin Shift to Low | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Indirect Bilirubin Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatine Kinase Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to High | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to Low | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatine Kinase Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to High | 9 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to Low | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Aspartate Aminotransferase Shift to High | 8 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to Low | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to Low | 6 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to Low | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to High | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Indirect Bilirubin Shift to Low | 12 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to High | 10 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Indirect Bilirubin Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to Low | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to High | 1 Participants |
Primary
Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)
Hematology parameters included complete blood cell count, with differential and platelet count, and absolute neutrophil count. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline values. The categories with at least one participant with shift from baseline in these parameters are reported.
Time frame: Parts A and C: Baseline up to Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Number analysed (n)' indicates the number of participants evaluable for the specified hematology parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to High | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils/Leukocytes Shift to High | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to High | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes/Leukocytes Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes/Leukocytes Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to Low | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to High | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to Low | 4 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils/Leukocytes Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to High | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to High | 9 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to High | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to High | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to Low | 5 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to Low | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to Low | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes/Leukocytes Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to Low | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes/Leukocytes Shift to High | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to Low | 4 Participants |
Primary
Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Activated Partial Thromboplastin Time (aPTT))
Activated partial thromboplastin time was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of aPTT at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of aPTT at baseline to high values postbaseline.
Time frame: Parts A and C: Baseline up to Day 269
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C:ITT set included all participants who received at least one dose of nusinersen in the current study. 'Number analysed (n)' signifies number of participants evaluable for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Activated Partial Thromboplastin Time (aPTT)) | Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Activated Partial Thromboplastin Time (aPTT)) | Shift to High | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Activated Partial Thromboplastin Time (aPTT)) | Shift to Low | 5 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Activated Partial Thromboplastin Time (aPTT)) | Shift to High | 1 Participants |
Primary
Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (International Normalized Ratio (INR))
INR was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of INR at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of INR at baseline to high values postbaseline. The category with at least one participant with shift from baseline in INR ratio is reported.
Time frame: Parts A and C: Baseline up to Day 269
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Number analysed (n)' signifies number of participants evaluable for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (International Normalized Ratio (INR)) | Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (International Normalized Ratio (INR)) | Shift to High | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (International Normalized Ratio (INR)) | Shift to Low | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (International Normalized Ratio (INR)) | Shift to High | 0 Participants |
Primary
Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Prothrombin Time (PT))
Prothrombin time was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of PT at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of PT at baseline to high values postbaseline.
Time frame: Parts A and C: Baseline up to Day 269
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. 'Number analysed (n)' signifies number of participants evaluable for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Prothrombin Time (PT)) | Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Prothrombin Time (PT)) | Shift to High | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Prothrombin Time (PT)) | Shift to Low | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Coagulation Parameters (Prothrombin Time (PT)) | Shift to High | 1 Participants |
Primary
Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs)
The ECGs were assessed by the investigator to be normal, abnormal and abnormal AE. The number of participants with ECG shifts from normal to each of the categorical values denoting an abnormal scan (abnormal not AE, abnormal AE) was assessed. Shift from baseline to worst post-baseline values were reported. The categories with at least one participant with shift from baseline in ECG are reported.
Time frame: Parts A and C: Baseline up to Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Baseline: Normal; Postbaseline: Normal | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Baseline: Normal; Post-baseline: Abnormal, not AE | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Baseline: Abnormal, not AE; Post-baseline: Abnormal, not AE | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Baseline: Unknown; Post-baseline: Abnormal, not AE | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Baseline: Unknown; Post-baseline: Abnormal, not AE | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Baseline: Normal; Postbaseline: Normal | 10 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Baseline: Abnormal, not AE; Post-baseline: Abnormal, not AE | 17 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Electrocardiograms (ECGs) | Baseline: Normal; Post-baseline: Abnormal, not AE | 12 Participants |
Primary
Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis
Urinalysis included assessments of urine total protein, specific gravity, pH, protein, glucose, ketones, bilirubin, blood, red blood cells (RBC), white blood cells (WBC), epithelial cells, bacteria, casts and crystals. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.
Time frame: Parts A and C: Baseline up to Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Number analysed (n)' indicates the number of participants evaluable for the specified urinalysis parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Protein High/positive | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | RBC High/positive | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Glucose High/positive | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | WBC High/positive | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to High | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Epithelial Cells High/positive | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Ketones High/positive | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Bacteria High/positive | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Occult Blood High/positive | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Bacteria High/positive | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Protein High/positive | 9 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Glucose High/positive | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Ketones High/positive | 8 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Occult Blood High/positive | 4 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | RBC High/positive | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | WBC High/positive | 2 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Shifts From Baseline in Urinalysis | Epithelial Cells High/positive | 4 Participants |
Primary
Parts A and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs)
An adverse event (AE) was any unfavorable & unintended sign (including an abnormal assessment such as an abnormal laboratory value), symptom, or disease temporally associated with use of an investigational product, whether or not related to investigational product. An SAE was any untoward medical occurrence that at any dose resulted in death, in the view of Investigator, placed participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. AE and SAEs were regarded as treatment-emergent if it was present prior to receiving first dose of nusinersen in this current study and subsequently worsened in severity or was not present prior to receiving first dose of nusinersen and subsequently appeared.
Time frame: Part A: From the first dose of the study drug up to Day 389, Part C: From the first dose of the study drug up to Day 361
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TEAEs | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TEAEs | 37 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (TESAEs) | TESAEs | 6 Participants |
Primary
Parts 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
Time frame: Parts A and C: Baseline up to Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts 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 | 0 percentage of participants |
| CS3B Matched Sham Control Group | Parts 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 | 0 percentage of participants |
Primary
Parts A and C: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements
Time frame: Parts A and C: Baseline up to Day 302
Population: Part A: Safety set included all participants who received at least one dose of nusinersen. Part C: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements | 0 percentage of participants |
| CS3B Matched Sham Control Group | Parts A and C: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements | 2.5 percentage of participants |
Secondary
Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale
PASA was assessed using a questionnaire. Caregivers were asked a series of questions regarding the mealtime behavior of the participant. The PASA questionnaire was developed to assess the signs and symptoms of dysphagia. It included 33 items across 4 domains: general feeding, drinking liquids, eating solid foods, & assessment of swallowing concerns. Items in domains general feeding, drinking liquids, & eating solid foods are assessed with 5 levels of response scored as 4-Never, 3-Rarely, 2-Sometimes, 1-Often, & 0-Always. Domain for assessing swallowing concerns has 4 levels of responses scored as: 3-Strongly Disagree, 2-Disagree, 1-Agree, 0-Strongly Agree. Higher score= improvement. A negative change from baseline=decrease in swallowing ability. From domains 'drinking liquids' and 'eating solid foods', 2 items (attempted to drink liquids and eat solid foods) were assessed as Yes/No, which are reported in another outcome measure.
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen. 'Number analysed (n)' signifies the number of participants evaluable for the specified parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Had Difficulty Feeding Themselves | 0.2 score on scale | Standard Deviation 0.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Had to Suction Excess Saliva/Drool | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Not Able Eat as Much as Would Like | 0.2 score on scale | Standard Deviation 0.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Not Able Eat Food Variety Would Like | -0.2 score on scale | Standard Deviation 0.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Been Tube-Fed | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Refused Liquid Foods | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Difficulty Drinking Thin Liquids | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Difficulty Drinking Thick Liquids | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Cough/Clear Throat Swallow Liquid Food | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Gagged or Choked on Liquid Food | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Retching/Vomiting Drinking Liquids | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Taken > 30 Minutes Drink Liquids | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Refused Solid Foods | 0.2 score on scale | Standard Deviation 0.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Difficulty Swallowing Soft Foods | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Difficulty Swallowing Solid Foods | -0.2 score on scale | Standard Deviation 0.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Had Difficulty Swallowing Pills | 0.2 score on scale | Standard Deviation 0.98 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Cough/Clear Throat Eat/Swallow Solid Food | 0.2 score on scale | Standard Deviation 0.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Had Food Stuck in Throat/Chest | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Gagged/Choked on Their Solid Food | 0.2 score on scale | Standard Deviation 0.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Retching/Vomiting Eating Solids | 0.2 score on scale | Standard Deviation 0.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Required Food to Be Cut Up | 0.7 score on scale | Standard Deviation 1.21 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Experienced/Shown Pain When Eating | 0.0 score on scale | Standard Deviation 0 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Has Taken > 30 Minutes Eat Solids | 0.3 score on scale | Standard Deviation 0.52 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Concern Child's Swallowing Ability | 0.8 score on scale | Standard Deviation 1.72 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Concerned About Child's Weight | 1.2 score on scale | Standard Deviation 1.6 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Concern Variety Foods Child Eats | 0.7 score on scale | Standard Deviation 1.51 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Concern Child Not Able Eat as Much | 1.3 score on scale | Standard Deviation 1.51 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Concern Child Unable Eat Variety | 1.3 score on scale | Standard Deviation 1.37 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Concern Not Get Goodness From Diet | 1.8 score on scale | Standard Deviation 1.17 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Concerned Child Aspirating Food | 1.0 score on scale | Standard Deviation 1.55 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Change From Baseline in the Parent Assessment of Swallowing Ability (PASA) Scale | Concern Child Choking When Eating | 1.2 score on scale | Standard Deviation 1.6 |
Secondary
Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods
PASA was assessed using a questionnaire. Caregivers were asked a series of questions regarding the mealtime behavior of the participant. The PASA questionnaire was developed to assess the signs and symptoms of dysphagia. It included 33 items across 4 domains that cover general feeding, drinking liquids, eating solid foods, and assessment of swallowing concerns. The 2 items of domains drinking liquids (attempted to drink liquids), eating solid foods (attempted to eat solid foods) were assessed as Yes/No. Data for the 2 items were summarized in terms of the shift from baseline.
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Attempted to Drink Liquid Foods | Baseline: No, Post-baseline: Yes | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Attempted to Drink Liquid Foods | Baseline: No, Post-baseline: No | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Attempted to Drink Liquid Foods | Baseline: Yes, Post-baseline: Yes | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Attempted to Drink Liquid Foods | Baseline: Yes, Post-baseline: No | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Attempted to Eat Solid Foods | Baseline: No, Post-baseline: Yes | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Attempted to Eat Solid Foods | Baseline: No, Post-baseline: No | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Attempted to Eat Solid Foods | Baseline: Yes, Post-baseline: Yes | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part A: Number of Participants With Shift From Baseline in PASA Scale Items - Attempted to Drink Liquids and Attempted to Eat Solid Foods | Attempted to Eat Solid Foods | Baseline: Yes, Post-baseline: No | 0 Participants |
Secondary
Part B: Change From Baseline in Growth Parameters (Body Height)
Body height was measured for all participants (infantile-onset and later-onset SMA).
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Body Height) | 8.0 cm | — |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in Growth Parameters (Body Height) | 10.25 cm | Standard Deviation 2.217 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Body Height) | 11.2 cm | — |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Body Height) | 6.9 cm | Standard Deviation 3.65 |
Secondary
Part B: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio)
As pre-specified in the protocol, head to chest circumference ratio was assessed only for the participants with infantile-onset SMA. Negative change from baseline indicates reduction in head-to-chest circumference ratio.
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio) | -0.03 ratio | Standard Deviation 0.085 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in Growth Parameters (Head-to-Chest Circumference Ratio) | -0.05 ratio | Standard Deviation 0.269 |
Secondary
Part B: Change From Baseline in Growth Parameters (Ulnar Length)
Ulnar length was measured in participants with later-onset SMA.
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Ulnar Length) | 2.8 cm | Standard Deviation 4.16 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in Growth Parameters (Ulnar Length) | 1.2 cm | Standard Deviation 1.39 |
Secondary
Part B: Change From Baseline in Growth Parameters (Weight for Age Percentile)
WHO child growth standards (2006) was used to calculate the weight for age percentile in the infantile-onset participants. The 2000 CDC Growth Charts was used to calculate the weight for age percentile for later-onset participants. Negative change from baseline indicates reduction in weight for age percentile
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Weight for Age Percentile) | -6.70 percentile | Standard Deviation 23.133 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in Growth Parameters (Weight for Age Percentile) | -3.60 percentile | Standard Deviation 35.202 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Weight for Age Percentile) | 9.1 percentile | Standard Deviation 20.23 |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Weight for Age Percentile) | -0.3 percentile | Standard Deviation 6.96 |
Secondary
Part B: Change From Baseline in Growth Parameters (Weight for Length Percentile)
As pre-specified in the protocol, weight for length percentile was assessed only for the participants with infantile-onset SMA. Negative change from baseline indicates reduction in weight for length percentile.
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Growth Parameters (Weight for Length Percentile) | -4.23 percentile | Standard Deviation 35.817 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in Growth Parameters (Weight for Length Percentile) | 6.05 percentile | Standard Deviation 40.119 |
Secondary
Part B: Change From Baseline in the PASA Scale
PASA was assessed using a questionnaire. Caregivers were asked a series of questions regarding the mealtime behavior of the participant. The PASA questionnaire was developed to assess the signs and symptoms of dysphagia. It included 33 items across 4 domains that cover general feeding, drinking liquids, eating solid foods, and assessment of swallowing concerns. Items in domains of general feeding, drinking liquids, & eating solid foods are assessed with 5 levels of response scored as 4-Never, 3-Rarely, 2-Sometimes, 1-Often, & 0-Always. Domain for assessing swallowing concerns has 4 levels of responses scored as: 3-Strongly Disagree, 2-Disagree, 1-Agree, 0-Strongly Agree. Higher score= improvement. A negative change from baseline=decrease in swallowing ability. As planned, for part B of the study, the PASA scale was assessed for the domain general feeding only.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. 'Number analysed (n)', signifies the number of participants evaluable for the specified parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Not Able To Eat Food Variety They Like | -1.6 score on scale | Standard Deviation 1.72 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Had To Suction Excess Saliva or Drool | -1.7 score on scale | Standard Deviation 1.38 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Been Tube-Fed | -1.8 score on scale | Standard Deviation 2.11 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Not Able To Eat As Much As Would Like | -1.6 score on scale | Standard Deviation 1.72 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Had Difficulty Feeding Themselves | -1.6 score on scale | Standard Deviation 1.81 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in the PASA Scale | Not Able To Eat As Much As Would Like | -0.2 score on scale | Standard Deviation 1.45 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in the PASA Scale | Not Able To Eat Food Variety They Like | -1.0 score on scale | Standard Deviation 1.18 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in the PASA Scale | Been Tube-Fed | -0.9 score on scale | Standard Deviation 1.76 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in the PASA Scale | Had To Suction Excess Saliva or Drool | -0.2 score on scale | Standard Deviation 1.58 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in the PASA Scale | Had Difficulty Feeding Themselves | -0.6 score on scale | Standard Deviation 1.55 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Not Able To Eat As Much As Would Like | 0.3 score on scale | Standard Deviation 0.95 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Had Difficulty Feeding Themselves | -0.4 score on scale | Standard Deviation 0.53 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Had To Suction Excess Saliva or Drool | 0.1 score on scale | Standard Deviation 0.38 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Not Able To Eat Food Variety They Like | 0.1 score on scale | Standard Deviation 0.69 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Been Tube-Fed | 0.0 score on scale | Standard Deviation 0 |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Not Able To Eat Food Variety They Like | -0.4 score on scale | Standard Deviation 0.93 |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Had To Suction Excess Saliva or Drool | 0.1 score on scale | Standard Deviation 0.36 |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Had Difficulty Feeding Themselves | 0.3 score on scale | Standard Deviation 0.73 |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Not Able To Eat As Much As Would Like | 0.0 score on scale | Standard Deviation 0.39 |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in the PASA Scale | Been Tube-Fed | 0.0 score on scale | Standard Deviation 0 |
Secondary
Part B: Change From Baseline in Urine Total Protein
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Urine Total Protein | -0.130 grams per liter (g/L) | Standard Deviation 0.4126 |
| CS3B Matched Sham Control Group | Part B: Change From Baseline in Urine Total Protein | -3.274 grams per liter (g/L) | Standard Deviation 14.1387 |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Change From Baseline in Urine Total Protein | -0.213 grams per liter (g/L) | Standard Deviation 0.2873 |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Change From Baseline in Urine Total Protein | 0.004 grams per liter (g/L) | Standard Deviation 0.0608 |
Secondary
Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen
The CHOP-INTEND test was designed to evaluate the motor skills of infants with significant motor weakness. It included 16 items (capturing neck, trunk, and proximal and distal limb strength), nine of which were scored 0, 1, 2, 3, or 4, five were scored as 0, 2, or 4, one was scored as 0, 1, 2, or 4, and one as 0, 2, 3, or 4 with higher scores indicating greater muscle strength and function. Total score was calculated as the sum of scores for each item. Total score ranged from 0 (worst possible score) and 64 (best possible score). The change from baseline to Day 302 in the total score was analyzed using the joint-rank methodology to account for mortality.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 37.3 score on scale |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Change From Baseline in CHOP-INTEND Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 38.3 score on scale |
p-value: =0.848495% CI: [-9.29, 11.299]ANCOVA
Secondary
Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Arm Circumference)
Arm circumference was measured in participants with infantile-onset SMA.
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Arm Circumference) | 0.45 cm | Standard Deviation 2.141 |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Arm Circumference) | 1.16 cm | Standard Deviation 2.144 |
Secondary
Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Chest Circumference)
Chest circumference was measured in participants with infantile-onset SMA.
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Chest Circumference) | 5.67 cm | Standard Deviation 4.868 |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Chest Circumference) | 6.64 cm | Standard Deviation 6.362 |
Secondary
Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Head Circumference)
Head circumference was measured in participants with infantile-onset SMA.
Time frame: Baseline, Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Head Circumference) | 4.52 cm | Standard Deviation 1.703 |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Change From Baseline in Growth Parameters (Head Circumference) | 5.50 cm | Standard Deviation 2.766 |
Secondary
Part B Infantile-onset SMA: Change From Baseline in HINE Section 2 Motor Milestones Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen
Section 2 of the HINE was used to assess motor milestones of the participants. It's composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. Within each of these categories, participants can progress from complete absence of a motor ability (the lowest level in each category) through multiple milestones (2 to 4 levels in each category) to the highest level within the category. The total motor milestones score for HINE section was calculated as the sum of each level and ranged from 0 to a maximum score of 26, higher score indicating improvement in motor milestones.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Change From Baseline in HINE Section 2 Motor Milestones Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 33.9 score on scale |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Change From Baseline in HINE Section 2 Motor Milestones Total Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 40.0 score on scale |
p-value: =0.173495% CI: [-2.693, 14.939]ANCOVA
Secondary
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
Section 2 of the HINE was used to assess motor milestones of the participants. It's composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. Within each category, 3 to 5 levels can be achieved. The total HINE section 2 motor milestones score was calculated as sum of each level & ranged from 0 to 26, higher score indicating improvement in motor milestones. A negative change from baseline indicates decline in motor milestones. Change from baseline in HINE section 2 motor milestones total score was compared to study CS3B (NCT02193074) matched sham control group, and was analysed using joint rank methodology.
Time frame: Baseline, Day 183
Population: As planned, analysis was performed in the Matched sham set. Matched sham set comprised of sham control participants of CS3B study (NCT02193074) identified by a matching algorithm and all of current study 50/28 mg participants that were included in ITT set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | 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 | 43.1 score on scale |
| CS3B Matched Sham Control Group | 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 | 16.5 score on scale |
p-value: <0.000195% CI: [18.812, 34.526]ANCOVA
Secondary
Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of Neurofilament Light Chain (NF-L) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group
The change from baseline in the plasma concentration of NF-L was compared to the study CS3B (NCT02193074) matched sham control group. Joint rank methodology was used for the analysis to account for mortality. The change from baseline data was reported in terms of least square geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline.
Time frame: Baseline, Day 183
Population: As planned, analysis was performed in the Matched sham set. Matched sham set comprised of sham control participants of the CS3B study (NCT02193074) identified by a matching algorithm and all of current study 50/28 mg participants that were included in the ITT set.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of Neurofilament Light Chain (NF-L) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | 0.06 ratio |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of Neurofilament Light Chain (NF-L) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | 0.70 ratio |
p-value: <0.0001ANCOVA
Secondary
Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen
The change from baseline in plasma concentration of NF-L was analysed using the joint rank methodology to account for mortality. The change from baseline data was reported in terms of LS geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline.
Time frame: Baseline, Day 64
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 0.23 ratio |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 0.12 ratio |
p-value: =0.00295% CI: [0.33, 0.78]ANCOVA
Secondary
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
Section 2 of HINE was used to assess motor milestones of participants. It's composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, & walking. Motor milestone responder: (i) a participant that demonstrated at least a 2-point increase in category of ability to kick or maximal score on that category or a 1-point increase in category of head control, rolling, sitting, crawling, standing, or walking, (ii) improvement in more categories than worsening, excluding category of voluntary grasp. For category of ability to kick, improvement, as defined in (i), worsening: at least a 2-point decrease or decrease to lowest possible score of no kicking. For other 6 categories, improvement: 1-point increase, worsening: at least 1-point decrease. Participants who died or withdrew from study were considered as non-responders. Difference in percentage of responders reported using Fisher's exact test.
Time frame: Baseline, Day 183
Population: As planned, analysis was performed in the Matched sham set. Matched sham set comprised of sham control participants of CS3B study (NCT02193074) identified by a matching algorithm and all of current study 50/28 mg participants that were included in the ITT set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | 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 | 58 percentage of responders |
| CS3B Matched Sham Control Group | 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 | 0 percentage of responders |
p-value: <0.000195% CI: [39.46, 71.81]Fisher Exact
Secondary
Part B Infantile-onset SMA: Percentage of Time on Ventilation
Time frame: Baseline up to Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Percentage of Time on Ventilation | 5.6 percentage of hours |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Percentage of Time on Ventilation | 7.5 percentage of hours |
Secondary
Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus 12/12mg Nusinersen
Permanent ventilation was defined as tracheostomy or ≥ 16 hours of ventilation/day continuously for \> 21 days in the absence of an acute reversible event. An independent EAC determined the date at which a participant was considered to have met the protocol-specified criteria of an acute reversible event. Only events that were adjudicated by the EAC as meeting the protocol defined criteria for permanent ventilation or death was included in the analysis. Participants who did not meet the endpoint definition were censored on the last occasion the participant was seen (either in-person visit or by telephone contact), irrespective of whether the participant has completed the full course of treatment and whether the participant has completed the study or permanently withdrawn.
Time frame: Screening up to Day 399
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 24.7 weeks |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus 12/12mg Nusinersen | NA weeks |
Secondary
Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group
Permanent ventilation was defined as tracheostomy or ≥ 16 hours of ventilation/day continuously for \> 21 days in absence of an acute reversible event. An independent endpoint adjudication committee (EAC) determined date at which a participant was considered to have met protocol-specified criteria of an acute reversible event. Only events that were adjudicated by the EAC as meeting the criteria for permanent ventilation or death were included in analysis. Participants who did not meet the endpoint definition were censored on the last occasion the participant was seen (either in-person visit or by telephone contact), irrespective of whether the participant has completed the full course of treatment and whether the participant has completed the study or permanently withdrawn.
Time frame: Screening up to Day 399
Population: As planned, analysis was performed in the Matched sham set. Matched sham set comprised of sham control participants of the CS3B study (NCT02193074) identified by a matching algorithm and all of current study 50/28 mg participants that were included in the ITT set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | NA weeks |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Time to Death or Permanent Ventilation for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | 19.1 weeks |
Secondary
Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus 12/12mg Nusinersen
Time to death was determined by an independent EAC. Participants who did not die were censored on the last occasion the participant was seen (either in-person visit or by telephone contact), irrespective of whether the participant has completed the full course of treatment and whether the participant has completed the study or permanently withdrawn.
Time frame: Screening up to Day 399
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | NA weeks |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | NA weeks |
Secondary
Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group
Time to death was determined by an independent EAC. Time to death (overall survival) was compared to the study CS3B (NCT02193074) matched sham control group.
Time frame: Screening up to Day 399
Population: As planned, analysis was performed in the Matched sham set. Matched sham set comprised of sham control participants of the CS3B study (NCT02193074) identified by a matching algorithm and all of current study 50/28 mg participants that were included in the ITT set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | NA weeks |
| CS3B Matched Sham Control Group | Part B Infantile-onset SMA: Time to Death (Overall Survival) for 50/28mg Nusinersen Versus CS3B Matched Sham Control Group | 33.6 weeks |
Secondary
Part B: Infantile SMA-onset: Change From (Ratio to) Baseline in CSF Concentration of NF-L
The change from baseline data was reported in terms of geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline.
Time frame: Baseline, Day 279
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Infantile SMA-onset: Change From (Ratio to) Baseline in CSF Concentration of NF-L | 0.06 ratio |
| CS3B Matched Sham Control Group | Part B: Infantile SMA-onset: Change From (Ratio to) Baseline in CSF Concentration of NF-L | 0.05 ratio |
p-value: =0.378595% CI: [0.62, 1.2]ANCOVA
Secondary
Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen
ACEND instrument was designed to quantify caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA. The ACEND included a total of seven domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance, and each domain comprised several items. The total score for each domain was calculated on a scale of 0 to 100, with a higher score indicating a decreased caregiver burden. A negative change from baseline indicates an increased caregiver burden.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Transfers Total Score | -0.0 score on scale |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Time Total Score | -4.4 score on scale |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Sitting/Play Total Score | 10.3 score on scale |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Emotion Total Score | 2.6 score on scale |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Mobility Total Score | 6.9 score on scale |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Finance Total Score | -7.7 score on scale |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Feeding/Grooming/Dressing Total Score | 7.9 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Finance Total Score | 7.8 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Feeding/Grooming/Dressing Total Score | 8.3 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Sitting/Play Total Score | 10.1 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Transfers Total Score | 9.9 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Mobility Total Score | 8.1 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Time Total Score | 11.9 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Assessment of Caregiver Experience With Neuromuscular Disease (ACEND) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | Emotion Total Score | 2.5 score on scale |
Secondary
Part B Later-onset SMA: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen
HFMSE scale was a tool used to assess motor function in children with later-onset 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. Each item is scored 0 (unable), 1 (performs with modification or adaptation) or 2 (able) and the total score was calculated by summing the 33 items and ranged from 0 to 66 with higher scores indicating greater motor function.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 2.6 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 3.3 score on scale |
Secondary
Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen
Participants were evaluated using PedsQL generic core scale & neuromuscular module. PedsQL generic core scale was used to calculate PedsQL inventory total score (PQLI), that included parent & participant's assessment on 4 dimensions: physical, emotional, social, & school functioning & psychosocial health. Each item was scored on 5-point ordinal scale (0=never to 4=almost always). PedsQL neuromuscular module (PQLN) measured HRQOL dimensions specific to with neuromuscular disorders, like SMA. Each item was scored on 5-point ordinal scale (0=never to 4=almost always). Dimensions were reversed scored & were linearly transformed to 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0) for both PQLI and PQLN, higher scores indicative of better health related quality of life. Total scale scores were calculated as sum of all items over number of items answered on all scales. If more than 50% of items/more within a dimension were missing, scale score was not computed.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. 'Number analysed (n)' indicates number of participants evaluable for the specified total score
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | PQLI-Total Score-Participant | -5.1 score on scale | Standard Error 4.73 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | PQLI-Total Score-Parent | -9.6 score on scale | Standard Error 4.32 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | PQLN-Total Score-Participant | -4.8 score on scale | Standard Error 3.41 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | PQLN-Total Score-Parent | -6.4 score on scale | Standard Error 4.25 |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | PQLN-Total Score-Parent | -0.7 score on scale | Standard Error 2.81 |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | PQLI-Total Score-Participant | 3.8 score on scale | Standard Error 2.61 |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | PQLN-Total Score-Participant | 10.4 score on scale | Standard Error 1.91 |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Pediatric Quality of Life Inventory™ (PedsQL) for 50/28mg Nusinersen Versus 12/12mg Nusinersen | PQLI-Total Score-Parent | -6.9 score on scale | Standard Error 2.96 |
Secondary
Part B Later-onset SMA: Change From Baseline in Revised Upper Limb Module (RULM) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen
RULM test was developed to assess upper limb functional abilities. RULM test: total 20 items. First item was assessed on 7-point scale (0:No useful function to 6-Can abduct both arms simultaneously, elbows in extension in full circle until they touch above head). This first item did not contribute to total score. For remaining 19 items, 18 items were assessed on 3-point scale: 0-Unable to achieve independently; 1-Modified method but achieves goal independent of physical assistance from another person; 2-Normal -achieves goal without any assistance. One remaining item was assessed as either 0 or 1. For each item, score was collected on left & right side. Derived total score=summing scores from these 19 individual items ranging from 0-if participant fails all activities to 37-if participant achieves all activities. If, for an individual item, response was recorded for both left & right side, highest score was used in calculating total score. Higher scores=increased upper limb function.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From Baseline in Revised Upper Limb Module (RULM) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 1.8 score on scale |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From Baseline in Revised Upper Limb Module (RULM) Score for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 2.5 score on scale |
Secondary
Part B Later-onset SMA: Change From (Ratio to) Baseline in CSF Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen
The change from baseline data was reported in terms of geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline.
Time frame: Baseline, Day 279
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From (Ratio to) Baseline in CSF Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 0.32 ratio |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From (Ratio to) Baseline in CSF Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 0.33 ratio |
Secondary
Part B Later-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen
The change from baseline data was reported in terms of geometric mean ratio to baseline. Lower ratios to baseline represent greater reductions in concentrations of NF-L from baseline.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 0.28 ratio |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Change From (Ratio to) Baseline in Plasma Concentration of NF-L for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 0.35 ratio |
Secondary
Part B Later-onset SMA: Number of New World Health Organization (WHO) Motor Milestones Achieved Per Participant for 50/28mg Nusinersen Versus 12/12mg Nusinersen
The WHO motor milestones were a set of six milestones in motor development: sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone and walking alone. The examiner recorded an overall rating of the participant's emotional state and then for each milestone one of the following four classifications: no (inability) - child tried but failed to perform the milestone, no (refusal) - child refused to perform despite being calm and alert, yes - child was able to perform the milestone, unable to test - could not be tested because of irritability, drowsiness or sickness. Mean of number of new milestones achieved per participant was calculated and reported in this outcome measure.
Time frame: Baseline, Day 302
Population: ITT set included all participants who were randomized and received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B Later-onset SMA: Number of New World Health Organization (WHO) Motor Milestones Achieved Per Participant for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 0.0 motor milestones per participant | Standard Deviation 0 |
| CS3B Matched Sham Control Group | Part B Later-onset SMA: Number of New World Health Organization (WHO) Motor Milestones Achieved Per Participant for 50/28mg Nusinersen Versus 12/12mg Nusinersen | 0.3 motor milestones per participant | Standard Deviation 1 |
Secondary
Part B: Number of Participants With Abnormalities in Vital Sign Parameters
Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. As pre-specified in protocol, the criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature \< 36.0 and \> 38.0 degrees C, pulse rate \< 60 and \> 100 bpm, systolic blood pressure \< 90, \> 140 and \> 160 mmHg, diastolic blood pressure \< 50, \> 90 and \> 100 mmHg and respiratory rate \< 12 and \> 20 breaths per minute. The categories with at least one participant with clinically relevant vital sign abnormalities are reported.
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Number analysed (n)' signifies number of participants evaluable for analysis of the specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature <36.0 C | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic Blood Pressure <90 mmHg | 24 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse Rate >100 bpm | 25 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >90 mmHg | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure <50 mmHg | 22 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory Rate >20 breaths/min | 25 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse Rate <60 bpm | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature >38.0 C | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory Rate <12 breaths/min | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >140 mmHg | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >100 mmHg | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >140 mmHg | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >100 mmHg | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure <50 mmHg | 44 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature <36.0 C | 23 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >90 mmHg | 8 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse Rate <60 bpm | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse Rate >100 bpm | 50 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory Rate >20 breaths/min | 50 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory Rate <12 breaths/min | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic Blood Pressure <90 mmHg | 47 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature >38.0 C | 6 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory Rate <12 breaths/min | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature <36.0 C | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature >38.0 C | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse Rate <60 bpm | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse Rate >100 bpm | 8 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic Blood Pressure <90 mmHg | 7 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >140 mmHg | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure <50 mmHg | 4 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >90 mmHg | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >100 mmHg | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory Rate >20 breaths/min | 8 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic Blood Pressure >140 mmHg | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory Rate >20 breaths/min | 16 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >100 mmHg | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Systolic Blood Pressure <90 mmHg | 10 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse Rate >100 bpm | 16 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Pulse Rate <60 bpm | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Respiratory Rate <12 breaths/min | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature >38.0 C | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Temperature <36.0 C | 7 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure >90 mmHg | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Abnormalities in Vital Sign Parameters | Diastolic Blood Pressure <50 mmHg | 10 Participants |
Secondary
Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs
Participants with abnormalities in neurological examinations recorded as AEs were reported.
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Muscular Weakness | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Tremor | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Bulbar Palsy | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Muscular Weakness | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Tremor | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Bulbar Palsy | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Bulbar Palsy | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Muscular Weakness | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Tremor | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Muscular Weakness | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Tremor | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Neurological Examination Abnormalities Reported as AEs | Bulbar Palsy | 0 Participants |
Secondary
Part B: Number of Participants With Shift From Baseline in ECGs
The ECGs were assessed by the investigator to be normal, abnormal and abnormal AE. The number of participants with ECG shifts from normal to each of the categorical values denoting an abnormal scan (abnormal not AE, abnormal AE) was assessed. Shift from baseline to worst post-baseline values were reported. The categories with at least one participant with shift from baseline in ECG are reported.
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Abnormal, not AE; Postbaseline: Abnormal, AE | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal ; Postbaseline: Abnormal, not AE | 9 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Unknown; Postbaseline: Abnormal, not AE | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal; Postbaseline: Abnormal, AE | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Abnormal, not AE; Postbaseline: Abnormal, not AE | 12 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal; Postbaseline: Normal | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal; Postbaseline: Abnormal, AE | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Abnormal, not AE; Postbaseline: Abnormal, AE | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Abnormal, not AE; Postbaseline: Abnormal, not AE | 30 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Unknown; Postbaseline: Abnormal, not AE | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal; Postbaseline: Normal | 7 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal ; Postbaseline: Abnormal, not AE | 10 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Abnormal, not AE; Postbaseline: Abnormal, AE | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal ; Postbaseline: Abnormal, not AE | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Abnormal, not AE; Postbaseline: Abnormal, not AE | 6 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal; Postbaseline: Abnormal, AE | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal; Postbaseline: Normal | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Unknown; Postbaseline: Abnormal, not AE | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Unknown; Postbaseline: Abnormal, not AE | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal; Postbaseline: Normal | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal ; Postbaseline: Abnormal, not AE | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Normal; Postbaseline: Abnormal, AE | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Abnormal, not AE; Postbaseline: Abnormal, not AE | 12 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shift From Baseline in ECGs | Baseline: Abnormal, not AE; Postbaseline: Abnormal, AE | 0 Participants |
Secondary
Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters)
Blood chemistry parameters included protein, albumin, creatinine, blood urea nitrogen, bilirubin (total and direct), alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, glucose, calcium, phosphorus, bicarbonate, chloride, sodium, potassium, cystatin C, and creatine kinase. Parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. Categories with at least one participant with shift from baseline in these parameters are reported.
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Number analysed (n)' signifies number of participants evaluable for analysis of the specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Direct Bilirubin Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Lactate Dehydrogenase Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to Low | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to High | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to High | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Gamma Glutamyl Transferase Shift to High | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to High | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to Low | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to Low | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Cystatin C Shift to Low | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to High | 8 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Cystatin C Shift to High | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Protein Shift to High | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Gamma Glutamyl Transferase Shift to Low | 7 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Albumin Shift to Low | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Indirect Bilirubin Shift to Low | 11 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Albumin Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Protein Shift to Low | 7 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatine Kinase Shift to High | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to High | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to High | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to High | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to Low | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Aspartate Aminotransferase Shift to High | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to Low | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to Low | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Magnesium Shift to High | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Cystatin C Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to High | 17 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Lactate Dehydrogenase Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to Low | 12 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Direct Bilirubin Shift to Low | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to High | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Aspartate Aminotransferase Shift to High | 9 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Gamma Glutamyl Transferase Shift to Low | 11 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to Low | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to High | 15 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Albumin Shift to Low | 13 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to High | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to Low | 4 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Protein Shift to Low | 9 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Gamma Glutamyl Transferase Shift to High | 5 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to High | 17 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Albumin Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to Low | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to Low | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to High | 14 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to Low | 5 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Indirect Bilirubin Shift to Low | 21 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to Low | 15 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to Low | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Magnesium Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to High | 16 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Cystatin C Shift to Low | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to High | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Protein Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatine Kinase Shift to High | 12 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Gamma Glutamyl Transferase Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Indirect Bilirubin Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatine Kinase Shift to High | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Cystatin C Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Cystatin C Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Albumin Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Albumin Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Aspartate Aminotransferase Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to Low | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Direct Bilirubin Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Gamma Glutamyl Transferase Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to High | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Lactate Dehydrogenase Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Magnesium Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Protein Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Protein Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Indirect Bilirubin Shift to Low | 3 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Lactate Dehydrogenase Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to Low | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Aspartate Aminotransferase Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Magnesium Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to High | 3 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alanine Aminotransferase Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatine Kinase Shift to High | 3 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Alkaline Phosphatase Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Phosphate Shift to High | 10 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Albumin Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Albumin Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Protein Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Cystatin C Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Cystatin C Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Urea Nitrogen Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Protein Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Creatinine Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Calcium Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Gamma Glutamyl Transferase Shift to High | 3 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Sodium Shift to Low | 3 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Glucose Shift to High | 6 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Gamma Glutamyl Transferase Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bilirubin Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Chloride Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Potassium Shift to High | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Direct Bilirubin Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Blood Chemistry Parameters) | Bicarbonate Shift to High | 0 Participants |
Secondary
Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters)
Hematology parameters included complete blood cell count, with differential and platelet count, and absolute neutrophil count. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Number analysed (n)' signifies number of participants evaluable for analysis of the specified hematology parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to High | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to Low | 7 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte/Leukocyte Shift to High | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils/Leukocytes Shift to High | 7 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to Low | 11 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to High | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to High | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to High | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte/Leukocyte Shift to Low | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte Atypical/ Leukocyte Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to Low | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to High | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte Atypical Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to Low | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to High | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocytes Shift to Low | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to Low | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to High | 7 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to Low | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocytes Shift to High | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to Low | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to Low | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to High | 11 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to Low | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocyte Mean Corpuscular Vol Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocyte Mean Corpuscular Vol Shift to Low | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to High | 10 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to High | 8 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to High | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to High | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to High | 13 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to Low | 13 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to High | 12 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to High | 14 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocytes Shift to Low | 10 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocytes Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to Low | 12 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to Low | 13 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to High | 15 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to High | 10 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to Low | 18 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils/Leukocytes Shift to High | 14 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to Low | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to High | 14 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte Atypical Shift to High | 5 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to Low | 7 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte Atypical/ Leukocyte Shift to High | 4 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte/Leukocyte Shift to Low | 5 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte/Leukocyte Shift to High | 7 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocyte Mean Corpuscular Vol Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to High | 15 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocyte Mean Corpuscular Vol Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to Low | 12 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to High | 13 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to Low | 20 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to Low | 4 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to High | 9 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to Low | 9 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to High | 17 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte/Leukocyte Shift to High | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocyte Mean Corpuscular Vol Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocyte Mean Corpuscular Vol Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocytes Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to High | 4 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte Atypical Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils/Leukocytes Shift to High | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to Low | 4 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte Atypical/ Leukocyte Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte/Leukocyte Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils Shift to High | 8 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Basophils/Leukocytes Shift to High | 9 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Eosinophils/Leukocytes Shift to High | 5 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hematocrit Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Hemoglobin Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocytes Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte Atypical Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte Atypical/ Leukocyte Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte/Leukocyte Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Lymphocyte/Leukocyte Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocyte Mean Corpuscular Vol Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocyte Mean Corpuscular Vol Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to Low | 6 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to Low | 9 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Monocytes/Leukocytes Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils/Leukocytes Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Platelets Shift to High | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Erythrocytes Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Leukocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Clinical Laboratory Parameters (Hematology Parameters) | Neutrophils Shift to High | 1 Participants |
Secondary
Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT)
aPTT was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of aPTT at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of aPTT at baseline to high values postbaseline.
Time frame: Baseline up to Day 279
Population: Safety set included all participants who received at least one dose of nusinersen. 'Number analysed (n)' signifies number of participants evaluable for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Shift to Low | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Shift to High | 7 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Shift to Low | 14 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Shift to Low | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (aPTT) | Shift to High | 1 Participants |
Secondary
Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR)
INR was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of INR at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of INR at baseline to high values postbaseline.
Time frame: Baseline up to Day 279
Population: Safety set included all participants who received at least one dose of nusinersen. 'Number analysed (n)' signifies number of participants evaluable for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Shift to Low | 5 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (INR) | Shift to High | 0 Participants |
Secondary
Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT)
Prothrombin time was evaluated to assess safety. Shift to low measured change in normal, high and unknown values of PT at baseline to low values postbaseline. Shift to high measured change in normal, low and unknown values of PT at baseline to high values postbaseline.
Time frame: Baseline up to Day 279
Population: Safety set included all participants who received at least one dose of nusinersen. 'Number analysed (n)' signifies number of participants evaluable for the specified category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Shift to Low | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Shift to High | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Shift to High | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Shift to Low | 6 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Coagulation Parameters (PT) | Shift to High | 1 Participants |
Secondary
Part B: Number of Participants With Shifts From Baseline in CSF Parameters
CSF parameters included cell count, total protein, and glucose. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. 'Number analysed (n)' signifies number of participants evaluable for analysis of the specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Glucose Shift to High | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Protein Shift to Low | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Erythrocytes Shift to High | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Leukocytes Shift to High | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Erythrocytes Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Protein Shift to High | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Leukocytes Shift to Low | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Glucose Shift to Low | 4 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Leukocytes Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Erythrocytes Shift to Low | 0 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Erythrocytes Shift to High | 9 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Glucose Shift to High | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Glucose Shift to Low | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Protein Shift to Low | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Leukocytes Shift to High | 5 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Protein Shift to High | 7 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Erythrocytes Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Glucose Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Leukocytes Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Leukocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Protein Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Glucose Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Protein Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Erythrocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Leukocytes Shift to High | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Glucose Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Glucose Shift to High | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Protein Shift to Low | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Protein Shift to High | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Erythrocytes Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Erythrocytes Shift to High | 7 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in CSF Parameters | Leukocytes Shift to Low | 1 Participants |
Secondary
Part B: Number of Participants With Shifts From Baseline in Urinalysis
Urinalysis included assessments of urine total protein, specific gravity, pH, protein, glucose, ketones, bilirubin, blood, RBC , WBC, epithelial cells, bacteria, casts and crystals. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available, by the Investigator. Here, shift to low indicates values that were normal, high, positive, abnormal or unknown at baseline and shifted to low values postbaseline. Shift to high indicates values that were normal, negative, absent, low or unknown at baseline and shifted to high values postbaseline. The categories with at least one participant with shift from baseline in these parameters are reported.
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Number analysed (n)' signifies number of participants evaluable for analysis of the specified parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | RBC High/positive | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Occult Blood High/positive | 4 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Protein High/positive | 12 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Crystals High/positive | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Ketones High/positive | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Glucose High/positive | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Bacteria High/positive | 10 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to Low | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to Low | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Casts High/positive | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Epithelial Cells High/positive | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | WBC High/positive | 3 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to High | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to High | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Epithelial Cells High/positive | 6 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to Low | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to High | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to Low | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to High | 8 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Protein High/positive | 27 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Glucose High/positive | 2 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Ketones High/positive | 16 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Occult Blood High/positive | 12 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | RBC High/positive | 3 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | WBC High/positive | 12 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Bacteria High/positive | 18 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Casts High/positive | 1 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Crystals High/positive | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Epithelial Cells High/positive | 5 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Casts High/positive | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Bacteria High/positive | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | WBC High/positive | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Occult Blood High/positive | 2 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Glucose High/positive | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to Low | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Protein High/positive | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Crystals High/positive | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Ketones High/positive | 4 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | RBC High/positive | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Ketones High/positive | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Occult Blood High/positive | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Casts High/positive | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | RBC High/positive | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | WBC High/positive | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to High | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Epithelial Cells High/positive | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Crystals High/positive | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Bacteria High/positive | 8 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Protein High/positive | 9 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Specific Gravity Shift to Low | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | Glucose High/positive | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With Shifts From Baseline in Urinalysis | pH Shift to High | 1 Participants |
Secondary
Part B: Number of Participants With TEAEs and TESAEs
AE was 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 was any untoward medical occurrence that at any dose resulted in death, in the view of the Investigator, placed the participant at immediate risk of death, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a birth defect. AE was regarded as treatment-emergent if it was present prior to receiving the first dose of nusinersen in the current study and subsequently worsened in severity or was not present prior to receiving the first dose of nusinersen and subsequently appeared.
Time frame: From the first dose of the study drug up to Day 399
Population: Safety set included all participants who received at least one dose of nusinersen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With TEAEs and TESAEs | TEAEs | 22 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With TEAEs and TESAEs | TESAEs | 18 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With TEAEs and TESAEs | TESAEs | 30 Participants |
| CS3B Matched Sham Control Group | Part B: Number of Participants With TEAEs and TESAEs | TEAEs | 45 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With TEAEs and TESAEs | TEAEs | 7 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Number of Participants With TEAEs and TESAEs | TESAEs | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With TEAEs and TESAEs | TEAEs | 14 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Number of Participants With TEAEs and TESAEs | TESAEs | 2 Participants |
Secondary
Part B: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part B: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements | 4 percentage of participants |
| CS3B Matched Sham Control Group | Part B: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements | 0 percentage of participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Part B: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements | 0 percentage of participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Part B: Percentage of Participants With a Postbaseline Platelet Count Below the Lower Limit of Normal on at Least 2 Consecutive Measurements | 0 percentage of participants |
Secondary
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
Time frame: Baseline up to Day 302
Population: Safety set included all participants who received at least one dose of nusinersen. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | 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 | 8 percentage of participants |
| CS3B Matched Sham Control Group | 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 | 0 percentage of participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | 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 | 0 percentage of participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | 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 | 0 percentage of participants |
Secondary
Part C: Change From Baseline in CHOP-INTEND Total Score
The CHOP-INTEND test was designed to evaluate the motor skills of infants with significant motor weakness. It included 16 items (capturing neck, trunk, and proximal and distal limb strength), nine of which were scored 0, 1, 2, 3, or 4, five were scored as 0, 2, or 4, one was scored as 0, 1, 2, or 4, and one as 0, 2, 3, or 4 with higher scores indicating greater muscle strength and function. Total score was calculated as the sum of scores for each item. Total score ranged from 0 (worst possible score) and 64 (best possible score).
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. It was planned to be assessed in infantile-onset SMA participants. 'Overall number of participants analyzed' signifies number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part C: Change From Baseline in CHOP-INTEND Total Score | 0.0 score on scale |
Secondary
Part C: Change From Baseline in HINE Section 2 Motor Milestones Total Score
Section 2 of the HINE was used to assess motor milestones of the infantile-onset SMA participants. It's composed of 8 motor milestone categories: voluntary grasp, ability to kick in supine position, head control, rolling, sitting, crawling, standing, and walking. Within each of these categories, participants can progress from complete absence of a motor ability (the lowest level in each category) through multiple milestones (2 to 4 levels in each category) to the highest level within the category. The 8 categories of HINE Section 2 can be summed to give a total score that ranges from 0 to 26.
Time frame: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. It was planned to be assessed in infantile-onset SMA participants. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Part C: Change From Baseline in HINE Section 2 Motor Milestones Total Score | 2.0 score on scale |
Secondary
Parts A and C: Change From Baseline in ACEND Total Score
ACEND instrument was designed to quantify caregiver impact experienced by parents/caregivers of children affected with severe neuromuscular diseases, including children with SMA. The ACEND included a total of seven domains assessing physical impact (including feeding/grooming/dressing, sitting/play, transfers, and mobility) and general caregiver impact (including time, emotion, and finance, and each domain comprised several items. The total score for each domain was calculated on a scale of 0 to 100, with a higher score indicating a decreased caregiver burden. A negative change from baseline indicates an increased caregiver burden.
Time frame: Parts A and C: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in ACEND Total Score | Transfers Total Score | -8.0 score on scale | Standard Deviation 12.39 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in ACEND Total Score | Time Total Score | 6.3 score on scale | Standard Deviation 14.25 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in ACEND Total Score | Sitting/Play Total Score | 0.0 score on scale | Standard Deviation 11.03 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in ACEND Total Score | Emotion Total Score | 11.1 score on scale | Standard Deviation 7.66 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in ACEND Total Score | Mobility Total Score | 7.1 score on scale | Standard Deviation 13.85 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in ACEND Total Score | Finance Total Score | 15.8 score on scale | Standard Deviation 14.29 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in ACEND Total Score | Feeding/Grooming/Dressing Total Score | 0.6 score on scale | Standard Deviation 2.51 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in ACEND Total Score | Finance Total Score | -2.4 score on scale | Standard Deviation 12 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in ACEND Total Score | Feeding/Grooming/Dressing Total Score | 0.8 score on scale | Standard Deviation 7.5 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in ACEND Total Score | Sitting/Play Total Score | -2.8 score on scale | Standard Deviation 14.48 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in ACEND Total Score | Transfers Total Score | -2.0 score on scale | Standard Deviation 15.34 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in ACEND Total Score | Mobility Total Score | -0.8 score on scale | Standard Deviation 15.01 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in ACEND Total Score | Time Total Score | 0.4 score on scale | Standard Deviation 10.47 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in ACEND Total Score | Emotion Total Score | -2.4 score on scale | Standard Deviation 9.44 |
Secondary
Parts A and C: Change From Baseline in HFMSE Total Score
HFMSE scale was a tool used 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. Each item is scored 0 (unable), 1 (performs with modification or adaptation) or 2 (able) and the total score was calculated by summing the 33 items and ranged from 0 to 66 with higher scores indicating greater motor function. Negative change from baseline indicates decrease in motor function.
Time frame: Parts A and C: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in HFMSE Total Score | -0.8 score on scale | Standard Deviation 3.76 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in HFMSE Total Score | 1.8 score on scale | Standard Deviation 3.99 |
Secondary
Parts A and C: Change From Baseline in PedsQL™ Total Score
Participants were evaluated using PedsQL generic core scale & neuromuscular module. PedsQL generic core scale was used to calculate PedsQL inventory total score (PQLI), that included parent & participant's assessment on 4 dimensions: physical, emotional, social, & school functioning & psychosocial health. Each item was scored on 5-point ordinal scale (0=never to 4=almost always). PedsQL neuromuscular module (PQLN) measured HRQOL dimensions specific to with neuromuscular disorders, like SMA. Each item was scored on 5-point ordinal scale (0=never to 4=almost always). Dimensions were reversed scored & were linearly transformed to 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0) for both PQLI and PQLN, higher scores indicative of better health related quality of life. Total scale scores were calculated as sum of all items over number of items answered on all scales. If more than 50% of items/more within a dimension were missing, scale score was not computed.
Time frame: Parts A and C: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. 'Number analysed (n)' signifies number of participants evaluable for the specified total score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in PedsQL™ Total Score | PQLI-Total Score-Participant | 6.1 score on scale | Standard Deviation 18.228 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in PedsQL™ Total Score | PQLI-Total Score-Parent | 3.3 score on scale | Standard Deviation 12.51 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in PedsQL™ Total Score | PQLN-Total Score-Participant | 9.9 score on scale | Standard Deviation 6.94 |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in PedsQL™ Total Score | PQLN-Total Score-Parent | 4.7 score on scale | Standard Deviation 5.72 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in PedsQL™ Total Score | PQLN-Total Score-Parent | 0.1 score on scale | Standard Deviation 9.65 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in PedsQL™ Total Score | PQLI-Total Score-Participant | 1.1 score on scale | Standard Deviation 9.74 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in PedsQL™ Total Score | PQLN-Total Score-Participant | 6.7 score on scale | Standard Deviation 13.11 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in PedsQL™ Total Score | PQLI-Total Score-Parent | 0.7 score on scale | Standard Deviation 8.15 |
Secondary
Parts A and C: Change From Baseline in RULM Total Score
RULM test was developed to assess upper limb functional abilities. RULM test: total 20 items. First item was assessed on 7-point scale (0:No useful function to 6-Can abduct both arms simultaneously, elbows in extension in full circle until they touch above head). This first item did not contribute to total score. For remaining 19 items, 18 items were assessed on 3-point scale: 0-Unable to achieve independently; 1-Modified method but achieves goal independent of physical assistance from another person; 2-Normal -achieves goal without any assistance. One remaining item was assessed as either 0 or 1. For each item, score was collected on left & right side. Derived total score=summing scores from these 19 individual items ranging from 0-if participant fails all activities to 37-if participant achieves all activities. If, for an individual item, response was recorded for both left & right side, highest score was used in calculating total score. Higher scores=increased upper limb function.
Time frame: Parts A and C: Baseline, Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Change From Baseline in RULM Total Score | 1.5 score on scale | Standard Deviation 1.52 |
| CS3B Matched Sham Control Group | Parts A and C: Change From Baseline in RULM Total Score | 1.2 score on scale | Standard Deviation 2.14 |
Secondary
Parts A and C: Number of Participants With WHO Motor Milestones Status
The WHO motor milestones were a set of six milestones in motor development: sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone and walking alone. The examiner recorded an overall rating of the participant's emotional state and then for each milestone one of the following four classifications: no (inability) - child tried but failed to perform the milestone, no (refusal) - child refused to perform despite being calm and alert, yes - child was able to perform the milestone, unable to test - could not be tested because of irritability, drowsiness or sickness.
Time frame: Parts A and C: Baseline up to Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With WHO Motor Milestones Status | Gain of one or More Motor Milestones | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With WHO Motor Milestones Status | No Change | 6 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A and C: Number of Participants With WHO Motor Milestones Status | Loss of one or More Motor Milestones | 0 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With WHO Motor Milestones Status | Gain of one or More Motor Milestones | 3 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With WHO Motor Milestones Status | No Change | 32 Participants |
| CS3B Matched Sham Control Group | Parts A and C: Number of Participants With WHO Motor Milestones Status | Loss of one or More Motor Milestones | 2 Participants |
Secondary
Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC)
The CGIC scale was a 7 point scale that required the clinician to assess how much the participant's illness had 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 indicates worsening of the condition. A separate CGIC assessment was performed by the Investigator (I) and caregiver (C). The categories with at least one participant having a CGIC score was reported.
Time frame: Parts A, B, and C: Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study. 'Overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. 'Number analyzed' indicates the number of participants evaluable for the specified category.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Very Much Improved | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | No Change | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Much Improved | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Worse | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Improved | 5 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Worse | 1 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | No Change | 0 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Improved | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Much Improved | 2 Participants |
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Very Much Improved | 0 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Much Improved | 10 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Improved | 3 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Very Much Improved | 3 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Improved | 3 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | No Change | 0 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Much Improved | 7 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Worse | 0 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Worse | 0 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Very Much Improved | 0 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | No Change | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Much Improved | 13 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | No Change | 1 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | No Change | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Improved | 3 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Very Much Improved | 18 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Very Much Improved | 8 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Improved | 7 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Worse | 0 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Much Improved | 20 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Worse | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | No Change | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Much Improved | 2 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Improved | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Worse | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Very Much Improved | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Much Improved | 3 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Improved | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | No Change | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Worse | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Very Much Improved | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | No Change | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Worse | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Very Much Improved | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Improved | 7 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Worse | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Much Improved | 8 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Very Much Improved | 0 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Much Improved | 5 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | No Change | 1 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Improved | 9 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Very Much Improved | 2 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Very Much Improved | 0 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Worse | 2 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | No Change | 14 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | No Change | 5 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Improved | 19 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Minimally Worse | 2 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Much Improved | 6 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-I | Much Improved | 5 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Clinical Global Impression of Change (CGIC) | CGIC-C | Minimally Improved | 9 Participants |
Secondary
Parts A, B and C: Number of Participants With Hospitalizations
Time frame: Parts A, B, and C: Baseline up to Day 302
Population: Parts A, B and C: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Hospitalizations | 1 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Hospitalizations | 19 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Hospitalizations | 26 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Hospitalizations | 3 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Hospitalizations | 6 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Hospitalizations | 12 Participants |
Secondary
Parts A, B and C: Number of Participants With Ventilator Use
Time frame: Parts A, B, and C: Screening up to Day 302
Population: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Ventilator Use | 0 Participants |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Participants With Ventilator Use | 9 Participants |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Participants With Ventilator Use | 22 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Ventilator Use | 4 Participants |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Participants With Ventilator Use | 5 Participants |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Participants With Ventilator Use | 8 Participants |
Secondary
Parts A, B and C: Number of Serious Respiratory Events
Time frame: Parts A, B, and C: Baseline up to Day 399
Population: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Serious Respiratory Events | 0 number of events |
| CS3B Matched Sham Control Group | Parts A, B and C: Number of Serious Respiratory Events | 34 number of events |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Number of Serious Respiratory Events | 60 number of events |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Serious Respiratory Events | 6 number of events |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Number of Serious Respiratory Events | 2 number of events |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Number of Serious Respiratory Events | 0 number of events |
Secondary
Parts A, B and C: Percentage of Time of Hospitalization
Time frame: Parts A, B, and C: Baseline up to Day 302
Population: Parts A, B and C: ITT set included all participants who received at least one dose of nusinersen in the current study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B: Infantile-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Percentage of Time of Hospitalization | 0 percentage of days |
| CS3B Matched Sham Control Group | Parts A, B and C: Percentage of Time of Hospitalization | 6.4 percentage of days |
| Part B: Later-Onset SMA: 12/12 mg Nusinersen | Parts A, B and C: Percentage of Time of Hospitalization | 1.9 percentage of days |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Percentage of Time of Hospitalization | 0.0 percentage of days |
| Part B: Later-Onset SMA: 50/28 mg Nusinersen | Parts A, B and C: Percentage of Time of Hospitalization | 0.0 percentage of days |
| Part C: Nusinersen 50/28 mg | Parts A, B and C: Percentage of Time of Hospitalization | 1.34 percentage of days |