This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered in pediatric participants with SMA and 2 SMN2 copies who previously received onasemnogene abeparvovec and experience a plateau or decline in function. Participants to be enrolled are children \<2 years of age genetically diagnosed with SMA.
<2 years of age at the time of informed consent
Confirmed diagnosis of 5q-autosomal recessive SMA, including genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the Survival of Motor Neuron 1 (SMN1) gene
Confirmed presence of two SMN2 gene copies as documented through laboratory testing
Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically
Previous or current enrolment in investigational study prior to initiation of study treatment
Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide
Concomitant or previous use of an anti-myostatin agent
Single group
Risdiplam
DrugParticipants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.
Change from Baseline in the Raw Score of Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) Gross Motor Score at 72 Weeks of Risdiplam Treatment
The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.
Percentage of Participants With Adverse Events
Percentage of Participants With Serious Adverse Events
Percentage of Participants With Treatment Discontinuation Due to Adverse Events
Change from Baseline in Bulbar/Swallowing Function Assessment as Measured by the Oral and Swallowing Abilities Tool (OrSAT) at 72 Weeks of Risdiplam Treatment and Over Time
The OrSAT is a validated assessment composed of a checklist of 12 questions assessing aspects of swallowing abilities thought to be clinically meaningful for a type 1 SMA population and developmentally appropriate for infants during the first months of life. Each item is graded with a score of 0 or 1, depending on the child's ability to perform the activity. As some items are age-dependent, the number of items to be used, and therefore the maximum score, changes with increasing age. In the infants younger than 6 months the maximum score is 7. For those between 6 and 9 months, maximum score is 10. For infants of 10 months or older, maximum total score is 12.
Change in Swallowing Function Assessment as Measured by the Pediatric Functional Oral Intake Scale (p-FOIS) Over Time
The p-FOIS is a 6-point scale that assesses feeding ability, 1= Nothing by mouth, 2= Tube dependent for all nutrition/hydration needs with minimal attempts at oral intake for experience and/or pleasure, 3= Tube dependent with consistent intake of food and/or fluid that meets some of the nutrition/hydration needs, 4= Total oral intake but special preparation required, e.g., thickened fluids, puréed diet (where not age-appropriate), 5= Total oral intake but requiring special conditions/modification, e.g., slow flow teat/side lying/pacing or specific food limitations, 6= Total, age-appropriate, oral intake with no restrictions. Higher score indicates higher level of function.
Change from Baseline in the Raw Score of BSID-III Gross Motor Score Over Time Under Risdiplam Treatment
The BSID-III is a standardized assessment commonly used to evaluate developmental functioning of infants and young children between 1 month and 42 months of age. The gross motor scale measures the movement of the limbs and torso. Items assess static positioning (e.g., sitting, standing); dynamic movement, including locomotion and coordination; balance; and motor planning. The gross motor scale consists of 72 items scored at 0 (unable to perform) or 1 (criteria for item achieved). A higher raw score indicates improvement.
Percentage of Participants With a Gross Motor Index Between 80-109 as Measured by the Peabody Developmental Motor Scale, Third Edition (PDMS-3) at 72 Weeks of Risdiplam Treatment and Over Time
The PDMS-3 is used to assess gross- and fine-motor skills in children from birth to 5 years. The PDMS-3 has 3 composite scores: Total Motor (combined scores of the core subtests) and two domain composites (Gross Motor and Fine Motor). By combining the results of subtests, these composite scores are considered to have stronger and better indexes of performance and, therefore, more reliable and valid than the subtests. Score for composite indexes range from \<70 (impaired or delayed) to \>129 (gifted or very advanced). Score of 80-89 indicate below average and 90-109 indicate average skills.
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