A Study to Learn About the Safety and Effects of Salanersen (BIIB115) When Given to Babies With Spinal Muscular Atrophy (SMA) Who Were Previously Treated With Onasemnogene Abeparvovec

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified July 2026 by Biogen
Sponsor
Biogen
Information Provided by (Responsible Party)
Biogen
Clinicaltrials.gov Identifier
NCT07444450
Other Study ID Numbers:
277SM301
First Submitted
February 25, 2026
First Posted
March 2, 2026
Last Update Posted
August 10, 2026
Last Verified
July 2026

ClinicalTrials.gov processed this data on August 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

The primary objective of the study is to evaluate the safety and tolerability of adding salanersen 6 months after OA in participants with genetically diagnosed SMA who received presymptomatic treatment with OA.

The secondary objectives are to evaluate the efficacy and effect on biomarkers of salanersen after OA, and to evaluate the pharmacokinetics (PK) of salanersen in participants with genetically diagnosed SMA who have received presymptomatic treatment with OA.

Condition or DiseaseIntervention/Treatment
Muscular Atrophy, Spinal
Drug: SalanersenDrug: Salanersen

Study Design

Study TypeInterventional
Actual Enrollment42 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Efficacy of Salanersen (BIIB115) After Onasemnogene Abeparvovec Treatment in Infants With Genetically Diagnosed Spinal Muscular Atrophy
Study Start Date2w 2d from now
Actual Primary Completion Date2yrs 11mos from now
Actual Study Completion Date6yrs 11mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Salanersen
Participants will receive a single dose of salanersen, 80 milligrams (mg) administered intrathecally on Day 1 in Part A. In Part B, participants will continue to receive four additional intrathecal doses of salanersen, 80 mg administered on Days 365, 730, 1095, and 1460.
Drug: Salanersen
Administered intrathecally
Sham Procedure
Participants will undergo a sham procedure on Day 1 in Part A. In Part B, participants will receive four intrathecal doses of salanersen, 80 mg administered on Days 365, 730, 1095, and 1460.
Drug: Salanersen
Administered intrathecally

Outcome Measures

Primary Outcome Measures
  1. Parts A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Secondary Outcome Measures
  1. Part B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
  2. Parts A and B: Change From Baseline in Plasma Levels of Neurofilament Light Chain (NfL)
    Blood will be collected to characterize changes in plasma NfL following treatment with salanersen. NfL is a protein released from damaged neurons and is a biomarker of neurodegeneration.
  3. Parts A and B: 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.
  4. Parts A and B: 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.
  5. Parts A and B: 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.
  6. Parts A and B: 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.
  7. Parts A and B: Percentage of Participants who Remain Free of Clinically Manifested Spinal Muscular Atrophy (SMA)
  8. Part B: Percentage of Participants who Develop Spinal Muscular Atrophy (SMA) Subtypes (Non-Sitters, Sitters and Walkers) as Assessed by the Investigator
  9. Part B: 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.
  10. Part B: 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.
  11. Parts A and B: Time to Death (Overall Survival)
  12. Parts A and B: 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 A and B: Concentration of Salanersen in Cerebrospinal Fluid (CSF)
  14. Parts A and B: Concentration of Salanersen in Serum

Eligibility Criteria

Ages Eligible for Study(Child)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Genetic documentation of 5q spinal muscular atrophy (SMA) homozygous gene deletion or mutation or compound heterozygous mutation.
2 copies of the survival motor neuron 2 (SMN2) gene.
Onasemnogene Abeparvovec (OA) dose given at ≤ 42 days of age and screening initiated less than 6 months from OA dosing.
OA dose given while participant was presymptomatic, per Investigator attestation. For this study, presymptomatic is defined as follows:
No clinical signs or symptoms at the time of OA dosing that are, in the opinion of the Investigator, strongly suggestive of SMA.
No absence of tendon reflexes (i.e., absence of all of biceps, knee and ankle tendons) at the time of OA dosing (e.g., Hammersmith Infant Neurological Examination (HINE) Section 1 or equivalent).
If Compound Muscle Action Potential (CMAP) data is available at the time of dosing, ulnar CMAP amplitude ≥ 2 millivolt (mV). Key
Exclusion Criteria
Any unresolved post-OA laboratory abnormalities defined as follows:
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be less than 2 × Upper Limit of Normal (ULN) while not receiving corticosteroids within 30 days prior to dosing with salanersen or sham procedure (repeat testing may be performed if necessary).
Evidence of thrombocytopenia, indicated by the platelet count being lower than the normal range for the laboratory.
Evidence of elevated troponin-I levels, identified as elevated post-OA, and has not returned to the normal range.
Confirmed demonstration of corrected QT interval, using Fridericia's correction method, of \> 450 milliseconds (ms).
Other than OA, any prior treatment with an approved SMA disease modifying therapy (e.g. nusinersen and/or risdiplam), a myostatin inhibitor therapy, or an investigational drug given for the treatment of SMA.
Steroid treatment administered for the purpose of treating complications following OA within 14 days prior to dosing with salanersen or sham procedure on Day 1. Note: Other protocol-defined inclusion/exclusion criteria will apply.

Contacts and Locations

Sponsors and CollaboratorsBiogen
Locations
Neurology Rare Disease Center | Flower Mound Texas, United States, 75028
Investigators
Study Director: Medical Director, Biogen