In this study, researchers will learn more about the safety and effects of BIIB115, also known as salanersen. Specifically, researchers will learn more about how salanersen works in babies who have already been treated with onasemnogene abeparvovec (OA) after being diagnosed with SMA.
Most people with SMA have changes in a gene called survival motor neuron 1, also known as SMN1. These changes lower the amount of SMN protein in their bodies. Without enough of this protein, motor neurons and muscles cannot work properly. A similar gene called SMN2 can help replace some of the lost SMN protein in the body. Salanersen works by helping the SMN2 gene to make more SMN protein.
OA works by replacing the missing or abnormal SMN1 gene. Sometimes, OA treatment may not work as well as expected. As a result, researchers are exploring whether giving another drug after OA could lead to better outcomes for people with SMA.
In this study, participants will have 2 SMN2 copies. The higher the copy number, the less severe the participant's SMA is. They will also have received treatment with OA by the time they were 42 days old and before showing any symptoms of SMA.
The main goal of the study is to learn more about the safety of giving salanersen to babies after OA treatment. Researchers will also learn more about whether salanersen can help make SMA symptoms less serious.
The main question researchers want to answer in this study is:
• How many participants have adverse events and serious adverse events after treatment?
Researchers will also learn more about:
* The effects on participants' motor symptoms and how many new movement milestones participants achieve. * How many participants stay free of SMA symptoms. * How much neurofilament protein is found in the blood after treatment. * How much salanersen gets into the fluid surrounding the brain and spinal cord. * How much salanersen gets into the blood. Researchers will use different tests to learn if motor symptoms are changing, including the World Health Organization (WHO) motor milestones and Hammersmith Infant Neurological Examination (HINE) Section 2 motor milestones.
The study will be done in 2 parts. Part A will last 1 year while Part B will last up to 4 years.
The study will be done as follows:
* First, participants will be screened to check if they can join the study. The screening period will be up to 6 months. Participants must have received OA treatment before the age of 42 days and started screening within 6 months of the OA dose. * Participants will be assigned to 1 of 2 treatment groups by chance. This is a "double blind" study which means neither the participants, study doctor, nor site staff will know which treatment group the participants are assigned to. * In this study, salanersen will be given as an intrathecal injection, which is an injection into the fluid surrounding the spine. This is done by a procedure called a lumbar puncture (LP) which involves inserting a needle into the lower back into the space around the spinal cord. * During Part A, one group will receive 80 milligrams (mg) of salanersen while another group receives a sham (fake) procedure. This means that a small needle prick will be done, but no injection will be given. * For each participant, the first visit of Part A will be 6 months after they receive OA treatment. * Part A will have up to 6 clinic visits and 2 phone calls and last up to 1 year. * During Part B, both groups of participants will receive 80 mg of salanersen once a year. * Part B will have up to 12 clinic visits and 14 phone calls and last up to 4 years. * In total, participants will be in the study for up to 5 and a half years.
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.
No clinical signs or symptoms at the time of OA dosing that are, in the opinion of the Investigator, strongly suggestive of SMA.
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).
Parallel
Salanersen
DrugAdministered intrathecally
Sham Procedure
Procedure/SurgeryA sham lumbar puncture is a skin-only needle prick at the usual lumbar puncture site. The needle does not enter the spinal canal.
Parts A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Part B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
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.
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.
