A Study to Learn About Salanersen's (BIIB115) Effects on Movement and Its Safety When Given Before Symptoms Appear in Babies With Genetically Diagnosed Spinal Muscular Atrophy (SMA)

For Part 1 of the study, the primary objective is to evaluate the clinical efficacy of salanersen in participants with genetically diagnosed SMA, and the secondary objective is to evaluate safety and tolerability, pharmacokinetics (PK), and effect on biomarkers after treatment with salanersen in participants with genetically diagnosed SMA.

For Part 2 of the study, the primary objective is to evaluate the long-term clinical efficacy of salanersen in participants with genetically diagnosed SMA, and the secondary objective is to evaluate the long-term safety and tolerability, PK, and effect on biomarkers after treatment with salanersen in participants with genetically diagnosed SMA.

Primary Outcome Measures

1. Part 1: Percentage of Participants with 2 Survival Motor Neuron 2 (SMN2) Copies Sitting Without Support (for at Least 10 Seconds)
2. Part 1: Percentage of Participants with 3 SMN2 Copies Walking Alone (for at Least 5 Steps)
3. Part 2: Percentage of Participants Attaining and Maintaining World Health Organization (WHO) Motor Milestones
   The WHO motor milestones will include six key developmental milestones: sitting without support, standing with assistance, hands-and-knees crawling, walking with assistance, standing alone, and walking alone.

Secondary Outcome Measures

1. Part 1: Percentage of Participants Attaining World Health Organization (WHO) Motor Milestones
   The WHO motor milestones will include six key developmental milestones: sitting without support, standing with assistance, hands-and-knees crawling, walking with assistance, standing alone, and walking alone.
2. Parts 1 and 2: Percentage of Participants Attaining Hammersmith Infant Neurological Examination Section 2 (HINE-2) Motor Milestones
   Section 2 of the HINE is used to assess motor milestones and includes 8 motor milestone categories: voluntary grasp (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3). Total HINE-2 score is the sum of points from each item and can range from 0 to 26, with higher scores depicting a better level of ability.
3. Parts 1 and 2: Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale
   The CHOP INTEND test is designed to evaluate the motor skills of participants with significant motor weakness. It includes 16 items (capturing neck, trunk, and proximal and distal limb strength) structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4. The total score ranges from 0-64, with higher scores depicting better motor function.
4. Parts 1 and 2: Change From Baseline in Compound Muscle Action Potential (CMAP) Amplitudes
   CMAP is a well validated method for tracking disease progression in neuromuscular disorders such as SMA and amyotrophic lateral sclerosis and has been proposed as a potential biomarker of a therapeutic effect in SMA. CMAPs will be performed for the following nerve-muscle pairs: ulnar-abductor digiti minimi and peroneal-tibialis anterior.
5. Part 1: Percentage of Participants who Remain Free of Clinically Manifested Spinal Muscular Atrophy (SMA)
6. Part 2: Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score
   The HFMSE is a tool used to assess motor function in individuals with SMA. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all 33 items, with a maximum score of 66 with higher scores depicting better ability to perform activities.
7. Part 2: Change From Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE)
   The HFMSE is a tool used to assess motor function in individuals with SMA. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability. The overall score is the sum of the scores for all 33 items, with a maximum score of 66 with higher scores depicting better ability to perform activities.
8. Part 2: Revised Upper Limb Module (RULM) Total Score
   The RULM is developed to assess upper limb functional abilities of participants with SMA. This test consists of a total of 20 upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function.
9. Part 2: Change From Baseline in Revised Upper Limb Module (RULM)
   The RULM is developed to assess upper limb functional abilities of participants with SMA. This test consists of a total of 20 upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function.
10. Part 2: Percentage of Participants who Develop Spinal Muscular Atrophy (SMA) Subtypes (Type 1, 2,3a and 3b) As Assessed by the Investigator
11. Parts 1 and 2: Time to Death (Overall Survival)
12. Parts 1 and 2: Time to Death or Permanent Ventilation
    Permanent ventilation is defined as tracheostomy or ≥16 hours ventilation/day continuously for \>21 days in the absence of an acute reversible event.
13. Parts 1 and 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
14. Parts 1 and 2: Concentration of Salanersen in Cerebrospinal Fluid (CSF)
15. Parts 1 and 2: Concentration of Salanersen in Serum
16. Parts 1 and 2: Change From Baseline in Plasma Levels of Neurofilament Light Chain (NfL)