A Study to Learn About the Effect of Nusinersen (BIIB058) Given as Injections to Children With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec (RESPOND)

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE 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; placed the participant at immediate risk of death (according to the investigator's judgment); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a birth defect or was a medically important event.

Hematology parameters included hemoglobin, hematocrit, erythrocytes, platelets, leukocytes, neutrophils, eosinophils, basophils, lymphocytes and monocytes count. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated values that were normal, low or unknown at baseline and shifted to high postbaseline values.

Blood chemistry parameters included bilirubin, direct and indirect bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, creatinine, urea nitrogen, cystatin C, sodium, potassium, chloride, bicarbonate, protein, albumin, calcium, phosphate, glucose, and creatine kinase. These parameters were flagged as low, normal, or high relative to the parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated 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.

Coagulation parameters included activated partial thromboplastin time, prothrombin international (Intl.) normalized ratio and prothrombin time. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated 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.

Urinalysis included assessments of specific gravity, pH, protein, glucose, ketones, direct bilirubin, occult blood, erythrocytes, leukocytes, epithelial cells, transitional epithelial cells, hyaline casts, ammonium biurate, amorphous crystals, calcium oxalate crystals, triple phosphate crystals and uric acid crystals. These parameters were flagged as low, normal, or high relative to parameter's normal range or as unknown if no result was available. Here, shift to low indicated values that were normal, high or unknown at baseline and shifted to low values postbaseline. Shift to high indicated 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.

Clinical significance of abnormalities in ECG was determined based on the investigator's discretion. Shift to abnormal indicated values that were normal or unknown at baseline and shifted to abnormal values postbaseline.

Vital sign assessment included temperature, heart rate, systolic blood pressure, and diastolic blood pressure. As pre-specified in SAP, the criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature > 38.0 degrees Celsius (C), heart rate increments or decrements of 15 and 30 beats per minute (bpm), systolic blood pressure increments or decrements of 20 and 40 [millimeters of mercury (mmHg)], diastolic blood pressure increments or decrements of 10 and 20 mmHg. The categories with at least one participant with clinically relevant vital sign abnormalities are reported.

The WHO motor milestones were a set of six milestones in motor development, all of which would be expected to be attained by 24 months of age in healthy children. The individual milestones are: sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone and walking alone.

The CHOP-INTEND test was designed to evaluate the motor skills of infants with significant motor weakness. It was evaluated for participants < 2 years of age at the time of informed consent and for participants 2 to ≤ 3 years of age at the time of informed consent if they did not achieve independent sitting prior to Screening. It included 16 items (capturing neck, trunk, and proximal and distal limb strength), nine of which were scored 0, 1, 2, 3, or 4 with greater scores indicating greater muscle strength, 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. 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). CHOP-INTEND assessments were discontinued once participants achieved a maximum score of 64 after Day 421, so the number of participants with data points decreased over time.

The HFMSE consists of 33 scored activities used to assess motor function in children with SMA. It was assessed only in participants aged 2 years and older. Participants were asked to do a specific activity (such as rolling) and they were then graded on the quality and execution of that movement on a scale of 0 = being unable, 1 = performed with some compensation, and 2 = unaided. The overall score is the sum of the scores for all activities and ranged from 0 to 66. Higher scores indicated increased motor function.

RULM test was developed to assess upper limb functional abilities. It was assessed only in participants aged 2 years and older. RULM test: total 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 to death or permanent ventilation is defined as the time from first dose to death or permanent ventilation (tracheostomy or 16 hours of ventilation/day continuously for > 21 days in the absence of an acute reversible event), whichever comes first. Time to death or permanent ventilation was estimated using the Kaplan-Meier method.

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.

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.