A Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Participants With Spinal Muscular Atrophy After Gene Therapy

A Phase IV Open-Label Study Evaluating the Effectiveness and Safety of Risdiplam Administered as an Early Intervention in Pediatric Patients With Spinal Muscular Atrophy After Gene Therapy

This is an open-label, single-arm, multicenter clinical study to evaluate the effectiveness and safety of risdiplam administered as an early intervention in pediatric participants with spinal muscular atrophy (SMA) and 2 SMN2 copies who have previously received onasemnogene abeparvovec. Participants are children < 2 years of age genetically diagnosed with SMA.

Inclusion Criteria:

• <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
• Has received onasemnogene abeparvovec for SMA no less than 13 weeks, but not more than months 30 weeks, prior to enrollment
• If treated with risdiplam prior to onasemnogene abeparvovec, risdiplam treatment must not have exceeded 3 weeks and must be discontinued 1 day prior to onasemnogene abeparvovec administration
• Has, in the opinion of the investigator, not experienced clinically significant decline in function from the time of onasemnogene abeparvovec administration

Exclusion Criteria:

• 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
• Participants requiring invasive ventilation or tracheostomy
• Participants requiring awake non-invasive ventilation or with awake hypoxemia (Arterial Oxygen Saturation [SaO2] <95%) with or without ventilator support
• Presence of feeding tube and an OrSAT score of 0
• Hospitalization for pulmonary event within the last 2 months, or any planned hospitalization at the time of screening
• Any major illness requiring hospitalization within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to first dose administration.