A Study Evaluating the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients With Spinal Muscular Atrophy Who Experienced a Plateau or Decline in Function After Gene Therapy

Study Overview
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Brief Summary
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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.

Official Title
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A Phase IV Open-Label Study Evaluating the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients With Spinal Muscular Atrophy Who Experienced a Plateau or Decline in Function After Gene Therapy

Conditions
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Muscular Atrophy, Spinal

Intervention / Treatment
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* Drug: risdiplam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: <2 years of age at the time of informed consent Confirmed diagnosis of 5q-autosomal recessive SMA Confirmed presence of two SMN2 gene copies Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically Has received onasemnogene abeparvovec for SMA no less than 3 months prior to enrollment In the opinion of the investigator, has demonstrated a plateau or decline in function post-gene therapy (with a duration of 6 months or less) documented by 2 individual time points in the functions as follows: swallowing AND one additional function/ability (respiratory, motor function, other) per appropriate expectation. Exclusion Criteria: Treatment with investigational therapy prior to initiation of study treatment Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information Concomitant or previous administration of a SMN2-targeting antisense oligonucleotide or SMN2 splicing modifier either in a clinical study or as part of medical care Requiring invasive ventilation or tracheostomy 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.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Risdiplam<br>Participants will receive risdiplam orally once daily for 72 weeks (Treatment Period). The Treatment Period will be followed by a 1-year Treatment Extension Period for a total study duration of 120 weeks (approximately 2.5 years) for each participant enrolled. | Drug: risdiplam<br>* Participants will receive risdiplam orally at the currently approved dose. The dose should be adapted for weight and age.<br>* Other names: RO7034067;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Baseline, Week 72 |